Polybrominated diphenyl ethers (PBDE) are a group of flame retardants used in a variety of artificial materials. Despite phasing out in most industrial countries, they persist in the environment and human tissues due to their persistence, lipophilicity, and bioaccumulation. Populational and experimental studies demonstrate male reproductive toxicity of PBDEs including increased incidence of genital malformations (hypospadias and cryptorchidism), altered weight of testes and other reproductive tissues, altered testes histology and transcriptome, decreased sperm production and sperm quality, altered epigenetic regulation of developmental genes in spermatozoa and altered secretion of reproductive hormones. A broad range of mechanistic hypotheses of PBDE reproductive toxicity has been suggested. Among these hypotheses, oxidative stress, disruption of estrogenic signaling, and mitochondria disruption are affected by PBDE concentrations much higher, than concentrations found in human tissues, making them unlikely links between exposures and adverse reproductive outcomes in the general population. Robust evidence suggests that at environmentally relevant doses, PBDEs and their metabolites may affect male reproductive health via mechanisms including AR antagonism and the disruption of a complex network of metabolic signaling.

Nicotine is a pharmacologically active component of tobacco which adversely affects the male reproductive system and fertility and Icariin (ICA) is the main active ingredient of Epimedium herba which has been used to treat several male reproductive problems. This study was aimed at investigating the protective or ameliorative effect of ICA against reproductive toxicity induced by intraperitoneal injection of nicotine in mice. Forty male mice were randomly divided into 4 groups: control, nicotine (0.75 mg/kg intraperitoneally), icariin (ICA, 75 mg/kg), and icariin plus nicotine (ICA + nicotine) group. After 35 days of treatment, the mice were weighed, sacrificed, and their reproductive organs were collected and examined for further studies. In the nicotine-treated group, epididymal sperm density and serum testosterone concentrations significantly decreased relative to the control group. Nicotine also caused oxidative damage as shown by significant reduction in the activities of antioxidant enzymes and an elevation in Malondialdehyde (MDA) levels. Icariin on the other hand, improved the reduction in sperm characteristics, hormone levels, and activities of antioxidant enzymes alterations observed in the nicotine treated mice. These findings indicate that the nicotine-induced reproductive toxicity and oxidative damages on male reproductive tissues can be effectively attenuated by icariin.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

The toxic effects of 4-octylphenol (4-OP) have been studied in species such as mouse and fish; however, the toxic effects of 4-OP in male specific niche cells has not been researched. In this study, we investigated the molecular mechanism of toxicity of 4-OP in mouse TM4 Sertoli cells. TM4 cells were treated with four concentrations (0, 10, 30, and 50 µM/mL) of 4-OP at time points 24, 48, and 72 h. Cell viability and apoptosis assay was conducted following exposure. 4-OP significantly decreased cell viability in a concentration- and time-dependent manner, and increased apoptosis. Quantitative PCR analysis showed that Bad, Bax, and Bak mRNA expression levels were higher in exposed cells than in the control, but Bcl-2 expression was decreased. Western blotting revealed that 4-OP induced activities of caspase-3 and phosphorylation of Bad in a concentration- and time-dependent manner. Additionally, cytochrome C protein did not colocalize with mitochondria marker dye by 24 h. Cytochrome c protein expression increased in a time-dependent manner with 50 µM/mL. These results suggest that 4-OP induces mitochondria-mediated apoptosis by regulation of Bcl-2 family proteins and caspase-3 activation in male Sertoli cells.

SET protein carries out multiple functions including those for protein phosphatase 2A (PP2A) inhibition, histone modification, DNA repair and gene regulation. SET overexpression has been detected in brain neurons of Alzheimer's disease patients, follicle theca cells of Polycystic Ovary Syndrome (PCOS) patients, and ovarian cancer cells, indicating that SET may play a pathological role for these disorders. SET transcript 2, produced by a specific promoter, represents a major transcript variant in different cell types. In this study, we characterized the transcriptional activation of human SET transcript 2 promoter in HeLa cells. Promoter deletion experiments and co-transfection assays indicated that ZFX, the Zinc finger and X-linked transcription factor, was able to transactivate the SET promoter. A proximal promoter region containing four ZFX-binding sites was found to be critical for the ZFX-mediated transactivation. Mutagenesis study indicated that the site located closest to the transcription start site accounted for most of the ZFX-mediated transactivity. Manipulation of ZFX levels by overexpression or siRNA knockdown confirmed the significance and specificity of the ZFX-mediated SET promoter activation. Chromatin immunoprecipitation results verified the binding of ZFX to its cognate site in the SET promoter. These findings have led to identification of ZFX as an upstream factor regulating SET gene expression. More studies are required to define the in vivo significance of this mechanism, and specifically, its implication for several benign and malignant diseases related to SET dysregulation.

Solvents are widely-used in all aspects of chemical sciences. One of the disadvantages of conventional solvents is attributed to the adverse impacts they pose on human health and ecological systems. Emerging class of solvents such as ionic liquids have been proposed to alleviate this problem. In this study, aquatic toxicity and biodegradability of two common industrial solvents are compared to those of two ionic liquids. Results from this study highlight the importance of solvent selection considering the information on the toxicity, biodegradability and fate and transport properties of selected solvents altogether.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

Tailings generated by mining account for the largest proportion of global waste from industrial activities. Copper is relatively uncommon world-wide, with low concentrations in sediments and waters, yet is very elevated around mining sites. On the Keweenaw Peninsula of Michigan, USA, jutting out into Lake Superior, 140 mines extracted native copper from the Portage Lake Volcanic Series, part of an intercontinental rift system. Between 1901-1932, two mills at Gay (Mohawk, Wolverine) sluiced 22.7 million metric tonnes (MMT) of copper-rich tailings (stamp sands) into Grand (Big) Traverse Bay. Here we examine: 1) 3D coastal elevation and reef bathymetry, 2) particle dispersal, 3) copper concentrations and leaching, plus 4) shoreline toxicity. About 10 MMT of tailings created a migrating coastal beach that stretches 7 km from the Gay pile to the Traverse River Seawall. Another 10 MMT are moving underwater on the coastal shelf, threatening Buffalo Reef, an important lake trout and whitefish breeding ground. Aerial photos, ALS (plane) LiDAR, and relatively inexpensive UAS (drone) surveys characterize shoreline structure and aid initial remediation. Because sands (natural beach quartz, stamp sand basalt) are silicates of similar density, particle dispersal is similar and challenging. However, stamp sand beaches contrast greatly with natural sand beaches in both physical profile and chemistry. Dispersing particles retain copper, and release toxic concentrations. Leaching is elevated by exposure to high DOC and low pH waters. Field experiments, shoreline seining, and benthic sampling confirm serious impacts on aquatic biota, supporting tailings removal.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

Global coverage and scale up of interventions to reduce newborn mortality remains low, though progress has been achieved in improving newborn survival in many low-income settings. An important factor in the success of newborn health interventions, and moving to scale, is appropriate design of community-based programs and strategies for local implementation. We report the results of formative research undertaken to inform the design of a newborn health intervention in Cambodia. Information was gathered on newborn care practices over a period of three months using multiple qualitative methods of data collection in the primary health facility and home setting. Analysis of the data indicated important gaps, both at home and facility level, between recommended newborn care practices and those typical in the study area. The results of this formative research have informed strategies for behavior change and improving referral of sick infants in the subsequent implementation study. Collection and dissemination of data on newborn care practices from settings such as these can contribute to efforts to advance survival, growth and development of newborns for intervention research, and for future newborn health programming.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those involving costly resource reallocation, and exhibiting endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

Phthalates are esters of Pthalic acid, compounds mainly used as plasticisers. Phthalates are widely used chemicals which are of significant research interest as their exposure causes various consequences for human health. There are several categories of phthalates extensively used in many commercial productions with diverse uses, physicochemical properties and toxicological effects. This chapter discusses the toxicity of Phthalates and its potential risks to human health.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Abstract: The use of IVF and related procedures has offered opportunities for couples to conceive who otherwise would remain childless. This technology is often viewed as the only option but is very expensive and not highly effective. ln an effort to improve access to care, governments are attempting to provide funding. In Ireland for example the Health Service Executive (HSE) has recently made IVF funding available through Regional Fertility Hubs. for couples who qualify. However, this policy has threatened a less invasive approach available in Ireland that can help many couples before IVF is employed. We propose that a newly emerging “medical treatment process” called Restorative Reproductive Medicine (RRM), combined with methods or apps that track biomarkers of the menstrual cycle as a prerequisite option for appropriate patients. To illustrate the effectiveness, we compared live birth rates from an established Irish RRM clinic that uses the ChartNeo app to HFEA (Human Fertilization and Embryology Authority) data, both from 2019. RRM treatment had a live birth rate of 40.4% compared to 24.4% per treatment cycle for IVF (P>0.0001). RRM twin pregnancy rate was 2.5% compared to 7% for IVF. RRM babies were usually full term and normal birth weight. Therefore, RRM is less expensive, less invasive, and more effective than IVF for most patients. This merits further evaluation and support by the HSE and other global authorities guiding health policy.

On Feb. 6^th, 2020, FDA implemented the enforcement priorities against all flavored, cartridge-based e-cigarettes other than menthol and tobacco flavors. This ban undermined the products’ attraction to vapers, so e-cigarette manufacturers added flavorants of other attractive flavors into tobacco-flavored e-cigarettes and re-established attractions. Both the sales of e-cigarettes and posts on social media suggested that the manufacturers’ strategies are likely “successful”. The re-established attraction causes not only a public health issue, but also threats to the health of individual vapers. Research has shown an increase in toxicity associated with the flavorants commonly used in flavored e-cigarettes that are likely added in tobacco-flavored e-cigarettes based on tobacco-derived and synthetic tobacco free nicotine, and these other flavors are associated with higher clinical symptoms not often induced by only natural traditional tobacco flavors. The additional health risks posed by the flavorants are pronounced even without considering the interactions of toxicology of the different tobacco flavorants, and more research should be done to understand the health risks thoroughly and to take proper actions accordingly for regulation of these emerging products.

We have developed a family of N-alkyl-nitrobenzamides that exhibit promising antitubercular ac-tivities. These compounds are a simplification of the structure of known inhibitors of DprE1, an essential Mtb enzyme and an emergent anti-TB target. The compounds were obtained by a simple synthetic methodology and their antitubercular, cyto-toxicity and stability were studied. The most active compounds were the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives. Lipophilicity was shown to be a main parameter modulating activity within each family. The most active compound presented MIC of 16 ng/mL and had in-termediate lipophilicities. The activity was also studied in a macrophage model of infection. In this model the compounds with chain lengths of 6 and 12 carbon atoms presented the best results, ex-hibiting activity profiles comparable to isoniazid. Docking studies performed suggested that the fit of our highly active compounds to the DprE1 binding pocket was very similar to the literature compounds. Furthermore, the metrics used in the analysis were able to distinguish between the families of the highly and least active compounds. Assessment of susceptibility over multiple species and computational together with the structure of the compounds are complementary information that supports DprE1 as a likely target of action for this type of compounds.

: Julia Creek dunnarts are an endangered species of carnivorous marsupials and the focus of multiple conservation strategies involving significant resources such as captive breeding programs. Despite the relevance for conservation, no study to date has focused on evaluating geriatric diseases in dunnarts. This study describes the pathology findings in a group of one wild and 35 captive-born, mostly geriatric Julia Creek dunnarts that failed to produce offspring over multiple breeding periods. A total of 20 females and 16 males were submitted for a postmortem examination, with ages ranging from 9-42 and 12-42 months for females and males, respectively. Of these, 10 had unremarkable findings. The most common condition in females was cystic glandular hyperplasia (n=8), typical of hormonal dysregulation profiles in senescence, particularly hyperestrogenism. Rarely, cutaneous disease represented by unidentified dermal round cell infiltrates was observed in females (n=2). Primary reproductive hormonal dysregulation was also suspected in males diagnosed with testicular degeneration, aspermatogenesis and/or atrophy (n=3). Cutaneous round cell infiltrates, possibly compatible with epitheliotropic lymphomas were seen in males (n=3), and 2/3 affected males also had concurrent testicular degeneration or atrophy, indicating male sex could be a predictor for lymphoid neoplasia in aged dunnarts especially in individuals with concurrent testosterone-luteinizing hormone dysregulation as it occurs in gonadectomized animals. The role of an underlying viral etiology is also explored. This study is the first to describe major spontaneous diseases in endangered aged Julia Creek dunnarts, providing an important understanding of senescence and geriatric diseases within a conservation context.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

Social biases may concentrate attention of researchers on a small number of well-known molecules/mechanisms leaving others underexplored. In accordance with this view, central to mechanistic toxicology is a narrow range of molecular pathways that are assumed to be involved in significant part of responses to toxicity. It is unclear, however, if there are other molecular mechanisms which play important role in toxicity events but are overlooked by toxicology. To identify overlooked genes sensitive to chemical exposures we used publicly available databases. First, we used data on published chemical-gene interactions for 17,338 genes to estimate their sensitivity to chemical exposures. Next, we extracted data on publication numbers per gene for 19,243 human genes from Find My Understudied Genes database. Threshold were applied to both datasets using our algorithm to identify chemically sensitive and chemically insensitive genes and well-studied and underexplored genes. 1,110 underexplored genes highly sensitive to chemical exposures were used in GSEA and Shiny GO analyses to identify enriched biological categories. Metabolism of fatty acids, amino acids, and glucose were identified as underexplored molecular mechanisms sensitive to chemical exposures. These findings suggest that future effort is needed to uncover the role of xenobiotics in the current epidemics of metabolic diseases.

Nanoparticles (NPs) are commonly used in healthcare and nano therapy, but their toxicity at high concentrations is well-known. Recent research has shown that NPs can also cause toxicity at low concentrations, disrupting various cellular functions and leading to altered mechanobiological behavior. While researchers have used different methods to investigate the effects of NPs on cells, including gene expression and cell adhesion assays, the use of mechanobiological tools in this context has been underutilized. This review emphasizes the importance of further exploring the mechanobiological effects of NPs, which could reveal valuable insights into the mechanisms behind NP toxicity. Such investigations could aid in developing new strategies to mitigate NP toxicity and improve their safety for biomedical applications. Moreover, understanding how NPs affect cell cytoskeletal functions through mechanobiology could have significant implications, including the development of innovative drug delivery systems and tissue engineering techniques. In summary, this review highlights the significance of incorporating mechanobiology into the study of NP toxicity and demonstrates the potential of this interdisciplinary field to advance our knowledge and practical use of NPs.

A survey study was conducted to analyze the reproductive and productive performances of four indigenous chicken breeds under different rearing system. Six villages located in Eastern Cape, South Africa were used for the study from July 2017 to June 2018. Data on clutch per year (CPY), hatchability (HATCH), egg per clutch (EGC), survivability at 10-12 weeks (SURV), egg per year (EPY), recovery period (RP), average age at production (AA), duration of rearing (DR), mortality, egg laying length (EGL), natural brooding period (NBP) and natural incubating period (NIP) were obtained from Seven thousand, five hundred and thirty eight (7538) indigenous chicken. Potchefstroom Kooekok is observed to be a good egg producing breed with 15.11±0.25eggs per clutch. Venda breed possess good mothering ability (hatchability) and high survivability with 86.03±0.31days and 82.70±0.26 days respectively. Naked Neck is known to be more prone to diseases with least (survivability) 60.08±0.25days. Village was positively correlated with EGC and HATCH, EGY and SURV at p≤0.01 and p≤0.05 respectively. Rearing system was positively correlated with EGC. Rearing system was positively correlated at p≤0.05 on EGC than CPY, HATCH, EGY and SURV. Breed and village interactions were significant at p≤0.05 on RP, AA, DR, EGL, NBP and NIP. Therefore, productive and reproductive traits of indigenous chicken differ across different rearing systems, breeds and villages.

Aluminum, a contentious trace element found in the environment, has been demonstrated to have harmful effects on both humans and animals. In contrast, Sempervivum tectorum, an evergreen plant, has been found to offer numerous beneficial effects for both humans and animals. Therefore, this study aims to assess the protective effect of S. tectorum on certain reproductive biomarkers in male rats exposed to aluminum. Thirty-five Wistar rats were randomly divided into five groups: NTC (no-treatment control) received distilled water; NC (negative control) received drinking water containing 1 mg/L aluminum sulfate (AS); E1 received 1 mg/L AS along with an 8% S. tectorum extract; PC (positive control) received only 8% S. tectorum extract; E2 received 1 mg/L AS for three months followed by 8% extract for one month. The study analyzed testosterone, LH, FSH, body weight, and the histological structure of the testis, epididymis, and prostate, as well as the levels of zinc, manganese, copper, and iron in these organs. Significant decreases in body weight, testis, and epididymis size were observed in the aluminum-exposed groups compared to the control, whereas these decreases were not significant in the S. tectorum-treated groups compared to the control. Aluminum exposure led to significant decreases in testosterone and LH levels, with FSH levels showing a non-significant decrease in males, which were mitigated significantly by the administration of the plant extract. Histological analysis revealed alterations in the testis, epididymis, and prostate of the AS-exposed groups, including necrosis of seminiferous tubule epithelium and Leydig cells in the testis, and basal epithelial necrosis in the epididymis and prostate. Aluminum levels increased in all organs studied, while levels of zinc, copper, iron, and manganese decreased, showing a negative and significant correlation with aluminum levels. The aqueous extract of S. tectorum demonstrated a protective effect on certain studied biomarkers in male rats affected by aluminum exposure.

At the end of mitosis the Mitotic Exit Network (MEN) pathway triggers complex tasks which mainly include the spindle disassembly and the nuclear envelopes assembly. In the course of telophase, which often lasts less than an hour and corresponds to only about 2% of the entire cell cycle’s duration, spatial and temporal cues are integrated to ensure that cytokinesis occurs after the genome has partitioned between mother and daughter cells. From the end of anaphase through telophase, sequential components of a Ras-like GTPase signaling pathway are controlled by a set of different spatial and temporal signals. Successful propagation of these signals through multi-step transduction requires a remarkable sequential coordination. By considering that cells lacking proper MEN function fail to exit from mitosis, I argue that in a hybrid genome impaired coordination between two diverged MENs is prone to result in critical mitotic defects, from late anaphase through telophase. The so-called HyMEN model of hybrid incompatibility depicted here can be regarded as an extension of the Bateson-Dobzhansky-Muller model of speciation, centered on the MEN.

With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenols, fiber, protein and fat-rich byproduct of walnut oil extraction, has been underexplored as a potential protein replacement in pig feed. In this study, we found that feeding large Diqing Tibetan pigs walnut kernel cake promoted adipose deposition and improved pork quality during pig growth. Transcriptome analysis revealed the upregulation of genes ANGPTL8, CCNP, ETV4, and TRIB3, associated with adipose deposition. Pathway analysis highlighted enrichment in adipose-deposition-related pathways, including PPAR, Insulin, PI3K-Akt, Wnt, and MAPK signaling. Further analysis identified DEGs (differentially expressed genes) positively correlated with adipose-related traits, such as PER2 and PTGES. Single-cell transcriptome data pointed to the specific expression of CD248 and PTGES in adipocyte progenitor/stem cells (APSCs), pivotal for adipocyte differentiation and adipose deposition regulation. This study demonstrates walnut kernel cake's potential to substitute soybean cake in pig feed, providing high-quality protein and promoting adipose deposition. It offers insights into feed protein replacement, human functional food, fat metabolism, and related diseases, with marker genes and pathways supporting pig breeding and pork quality improvement.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

Genes encoding retinol binding protein 4 (RBP4), follicle stimulating hormone subunit beta (FSHB) and epidermal growth factor (EGF) have been proposed as candidate genes for reproduction traits in pigs. The study presented in this paper aimed to find associations between variants of these genes and reproduction traits in pigs reared in Poland. Investigation included Polish Large White x Polish Landrace (n=288) and Yorkshire (n=195) sows. Individual genotypes were determined by means of PCR-RFLP (single nucleotide polymorphism in RBP4, FSHB) or PCR (insertion/deletion in EGF) methods. Obtained result showed that RBP4 variants were related to total number born (TNB) and number born alive (NBA) in 1st, 2nd and 5th parities, FSHB to TNB and NBA in first two parities, however EGF with both traits in all parities (P≤0.05 or P≤0.01). In case of RBP4 gene, heterozygous genotype (AB) was favorable for analyzed traits, however in case of FSHB and EGF homozygous genotype, AA and BB respectively. Obtained results indicate that polymorphism in three analyzed genes is associated with important reproductive traits of pigs kept in Poland.

The use of probiotics in reproductive-related dysbiosis is an area of continuous progress due to the growing interest from clinicians and patients suffering recurrent reproductive microbiota disorders. An imbalance in the natural colonization sites related to reproductive health: vaginal, cervicovaginal, endometrial and also pregnancy-related altered microbiota could play decisive role in reproductive outcomes. Oral and vaginal administrations are in continuous discussion regarding the clinical effect pursued, but probiotics as oral supplement therapy is the route administration better studied. To complement and summarise with qualitative and quantitative information of vaginal probiotics clinical studies, the main objective of this work was to retrieve the standardised protocols commonly used and their microbiota modulation capacities. The studies selected were related to treat bacterial vaginosis (BV) as the most commonly disorder, few studies on vulvovaginal candidiasis (VVC) and also administration to stabilise microbiota before in vitro fertilisation (IVF). Probiotic doses administered were similar to oral probiotics protocols, ranging from ≥ 107 CFU/day to 2.5 x 1010 CFU/day, and variable regarding posology duration from 1 day to 12 weeks, being 1 week commonly applied. Moderate modulation was achieved regarding the relative abundance decrease of abnormal microbiota, coinciding with parallel increase in Lactobacillus species.

(1) Background: In recent years, an innovative approach has emerged in the field of toxicology for managing acute intoxications caused by lipophilic substances: intravenous lipid emulsions (ILE). Through numerous experiments and case reports, the efficacy of lipid emulsions in counteracting toxicities induced by lipophilic agents, including a significant number of antiepileptic drugs (AE), has become increasingly evident. (2) Methods: Data spanning a 10-year period (2010-2020) was analyzed by searching through multiple scientific publication platforms like PubMed, Science Direct, Research Gate, and Springer Link. The study focused on reviewing relevant case reports detailing successful Intravenous lipid emulsion (ILE) administration in pa-tients with acute intoxications with antiepileptics, specifically examining the impact of fat emul-sions on neurological status, Glasgow Coma Scale (GCS) scores, and corrected QT interval con-cerning hemodynamic instability. (3) Results: The typical symptoms of antiepileptic toxicity in-clude central nervous system depression, ataxia, and nystagmus. Intravenous lipid emulsion ap-plication resulted in an increase in Glasgow Coma Scale scores and enhanced recovery from drug intoxication. (4) Conclusions: This study provides a comprehensive overview of the potential utility of ILE as a component to antidote therapy in cases of acute AE poisoning involving neurotropic drugs. The process involves the engagement of various mechanisms of antitoxic activity.

Background: Reproductive coercion and abuse (RCA) is a hidden form of violence against women. It includes behaviours intended to control or dictate a woman’s reproductive autonomy, for the purpose of either preventing or promoting pregnancy. Main text: In this commentary, we argue that there is a lack of conceptual clarity around RCA that is a barrier to developing a robust evidence base. Furthermore, we suggest that there is a poor understanding of the way that RCA intersects with other types of violence (intimate partner violence; sexual violence) and – as a result – inconsistent definition and measurement in research and practice. To address this, we propose a new way of understanding RCA that centres perpetrator intent and the presence of fear and control. Recommendations for future research are also discussed. Conclusion: We suggest that IPV and SV are the mechanisms through which RCA is perpetrated. In other words, RCA cannot exist without some other form of co-occurring violence in a relationship. This has important implications for research, policy and practice including for screening and identification of women in reproductive healthcare settings.

Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries [1]. In addition to reduced fertility, people with PCOS have a higher risk of obesity, insulin resistance, and metabolic disease [1], all comorbidities that are associated with mitochondrial dysfunction. This review summarizes human and animal data that report mitochondrial dysfunction and metabolic dysregulation in PCOS to better understand how mitochondria impact reproductive organ pathophysiology. This in-depth review considers all the elements regulating mitochondrial quantity and quality, from mitochondrial biogenesis under transcriptional regulation of both the nuclear and the mitochondrial genome, to the ultrastructural and functional complexes that regulate cellular metabolism and reactive oxygen species production, to dynamics which regulate subcellular interactions that are key to mitochondrial quality control. When any of these mitochondrial functions are disrupted the energetic equilibrium within the cell changes, cell processes can fail, and cell death can occur. If this process is ongoing, it affects tissue and organ function to cause disease. The objective of this review is to consolidate and classify a broad number of PCOS studies to understand how various mitochondrial processes impact reproductive organs including the ovary (oocyte and granulosa cell), uterus, placenta, and circulation to cause reproductive pathophysiology. A secondary objective is to uncover the potential role of mitochondria in transgenerational transmission of PCOS and metabolic disorders.

Use of probiotic lactobacilli has been proposed as a strategy to mitigate damage associated to exposure to toxic metals. Their protective effect against cationic metal ions, such as those of mercury or lead, is believed to stem from their chelating and accumulating potential. However, their retention of anionic toxic metalloids, such as inorganic arsenic, is generally lower. Through the construction of mutants in phosphate transporter genes (pst) in Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains, coupled with arsenate [As(V)] uptake and toxicity assays, we determined that the incorporation of As(V), which structurally resembles phosphate, is likely facilitated by phosphate transporters. Surprisingly, inactivation in Lc. paracasei of PhoP, the tran-scriptional regulator of the two-component system PhoPR, a signal transducer involved in phosphate sensing, led to an increased resistance to arsenite [As(III)]. In comparison to the wild type, the phoP strain exhibited no differences in the ability to retain As(III), and there were no observed changes in the oxidation of As(III) to the less toxic As(V). These results reinforce the idea that specific transport, and not unspecific cell retention plays a role in As(V) biosorption by lactobacilli, while they reveal an unexpected phenotype for the lack of the pleiotropic regulator PhoP.

This article aims to provide a comprehensive understanding of vaping from various perspectives that contributes to the origin, development, achievement, and consequences of the greed of e-cigarette manufacturers. In our analysis, multiple elements of the social landscape, including economic, cultural, moral, psychological, and philosophical dimensions, contributed to the origin and development of the vaping greed and shaped people’s behaviors. Further discussion was made on how the specific characteristics of e-cigarette products and the marketing strategies of the companies, especially social media marketing, fostered the growth of such greed. Through interviews, we have also discussed the unfolding of this greed within the community of teenage vapers. The growth of the vaping greed was manifested in the large market share taken by the companies, but these all significantly harm people’s health and the communities. Nicotine and other chemicals in e-liquids promote each other’s negative effects in the mechanism leading to pulmonary symptoms and addiction, which are not limited to the physical level. We described that addiction could be transgenerational and can induce trauma both at an individual level and a community level. Overall, the greed of the vaping industry is a very complex system. The treatment of the greed shall be complicated as well: Besides the public health measures taken to treat the symptoms of the greed, we should educate individuals to be aware of their unfulfilled needs to regain authenticity and establish an infallible authority to enforce universal morality, which eradicates the complications of addiction and the root of the capitalists’ greed, respectively.

Increasing environmental distress is associated with a growing asthma incidence and, with no treatments available, montelukast (MTK) – an antagonist of the cysteinyl leukotrienes receptor 1 – is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions. Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as modulator of leukotriene pathways and systematize the knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.

Silicon nanoparticles (SiNPs) are highly promising for biological and biomedical applications, including bioimaging, due to their unique opltical properties (i.e. strong fluorescence and very high photostability). Their low or negligible in vitro toxicity has been reported, but in vivo toxicity and biological effects of SiNPs are still uncertain. Uncoated SiNPs were dispersed in distilled water via sonication, and their rapid aggregation was observed (319.0 ± 2.4 nm particle size). In vivo toxicity was studied using Danio rerio embryos and larvae. Rapid aggregation in their incubation medium was observed; besides that, SiNPs at 25 mg/L or higher concentration induced swim bladder malformation and/or death of the fish. The estimated LC50 value for 7-day larvae was 180 mg/L. This is the first in vivo toxicity study of uncoated and unfunctionalized SiNPs. To achieve better stability in biological media and lower toxicity, SiNPs should be covered with hydrophilic layers, but their absorption by cellular membranes may be weaker in this case.

Global climate change, particularly rising sea surface temperatures, profoundly impacts coral ecosystems, disrupting reproduction synchrony, symbiotic relationships with algae from the Symbiodiniceae family, and causing widespread bleaching and mortality among coral populations.  Oculina patagonica, a temperate scleractinian coral dominant in Mediterranean coastal waters, tolerates an annual temperature range of 10- 31°C. Moreover, in the past three decades, sea surface temperatures have rapidly risen in the Eastern Mediterranean Sea. O. patagonica offers insight into evolutionary adaptation to rapid environmental changes. This study investigated the effects of temperature changes on O. patagonica reproductive development, synchrony, and thermal sensitivity. Monthly monitoring of O. patagonica colonies for a year reveals no disruption in gonad development compared to previous studies, suggesting an unaffected sexual reproduction capacity. Thermal performance

Multiple indicators have been used to assess the degree of exposure of fish to anthropogenic chemicals in their stream habitats. We hypothesized that brook stickleback (Culaea inconstans) in a headwater stream receiving urban and agricultural runoff (South Fork Whitewater River, SFWR) would exhibit poorer condition, reduced reproductive fitness, and greater left side-to-right side morphological asymmetry (i.e., fluctuating asymmetry or FA) than would fish from a nearby headwater stream with a forested drainage basin (Garvin Brook). Male and female fish were collected from both streams just prior to spawning in 2013-2015. In 2013 and 2014, fish were assessed for overall condition (Fulton’s K) and internal measures of condition (hepatosomatic index, HSI) and reproductive fitness (gonadosomatic index [GSI], total egg count, egg weight). In 2015, measurements of head length, jaw length, eye diameter, pectoral fin length, and pelvic fin length were made on both sides of each fish for use in assessing degree of FA. We observed declining condition with fish size, increased liver size, and reduced egg counts and egg size in female brook stickleback in SFWR relative to those from Garvin Brook. SFWR females had significantly higher FA than Garvin females for all structures assessed except pelvic fin length. FA also was slightly higher for all structures in SFWR males compared to Garvin males, but differences were not significant. A composite FA index combining all measurements from an individual fish into a single value displayed highly significant differences for female fish (SFWR FA >> Garvin FA), but not for male fish (SFWR FA = Garvin FA). Exposure of brook stickleback to reduced water quality in SFWR during early development appears to increase morphological asymmetry in female (but not male) fish, and continuing exposure to compromised water quality throughout life impacts both general condition and reproductive fitness of stickleback, especially older female fish, in SFWR.

Ovarian endometriomas have a negative impact on a patient’s reproductive potential and likely cause a reduction in ovarian reserve. The most commonly employed ovarian reserve parameters are anti-mullerian hormone (AMH) and antral follicular count (AFC). Surgical management options of endometrioma include cystectomy, ablative methods, ethanol sclerotherapy and combined techniques. The optimal surgical approach remains a matter of debate. Our review aimed to summarize the literature on the impact of surgical management of endometrioma on AMH, AFC and fertility outcomes. Cystectomy may reduce recurrence rates and increase chances of spontaneous conception. However, a post-operative reduction in AMH is to be anticipated, albeit there is evidence of recovery during follow-up. The reduction in ovarian reserve is likely multi-factorial. Cystectomy does not appear to significantly reduce, and may even increase, AFC. Ablative methods achieve an ovarian tissue-sparing effect and improved ovarian reserve, compared to cystectomy, has been demonstrated. A single study reported on AMH and AFC post- sclerotherapy and both were significantly reduced. AMH levels may be useful in predicting the chances of conception post-operatively. None of the aforementioned approaches has clearly demonstrated a superiority in terms of overall chances of conception. Surgical management of endometrioma may, overall, improve probability of pregnancy. Evidence on its value before medically-assisted reproduction (MAR) is conflicting, however, a combination of surgery followed by MAR may achieve the optimal fertility outcome. In view of the complexity of available evidence, individualisation of care, combined with optimal surgical technique, is highly recommended.

Hormones must be balanced and dynamically controlled for the Female Reproductive Tract (FRT) to function correctly during the menstrual cycle, pregnancy, and delivery. Gamete selection and successful transfer to the uterus, where it implants and pregnancy occurs, is supported by the mucosal epithelial lining of the FRT ovaries, uterus, cervix, fallopian tubes, and vagina. Successful implantation and placentation in humans and other animals rely on complex interactions between the embryo and a receptive female reproductive system. The FRT's recent breakthroughs in three-dimensional (3D) organoid systems now provide critical experimental models that match the organ's physiological, functional, and anatomical characteristics in vitro. This article summarizes the current state of the art on organoids generated from various parts of the FRT. The current analysis examines recent developments in the creation of organoid models of reproductive organs, as well as their future directions.

Immune Checkpoint Inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and Tumour Mutational Burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.

Reproductive coercion and abuse is a hidden and poorly recognised form of violence against women. It refers broadly to behaviours that interfere with or undermine a person’s reproductive autonomy, specifically to promote or prevent pregnancy. Reproductive coercion and abuse can involve physical, sexual, financial or psychological abuse in order to achieve these aims, and is overwhelmingly perpetrated by men against women. As an emerging field of scholarship, conceptual understanding of reproductive coercion and abuse is still in its infancy; however, it is often described as being linked to coercive control. In this article, we seek to highlight the complexity of this relationship through qualitative analysis of in-depth interviews with 30 victim/survivors in Australia recruited from the community, focusing on their perceptions of the perpetrator’s motivations. Our analysis suggests that perpetrator motivations can range from entitlement and self-interest to a deep desire for domination and entrapment. Pregnancy preventing behaviour was more likely to be linked with entitlement and self-interest, whereas pregnancy promoting behaviour tended to be described by participants in relationships where there was a broader pattern of ongoing control and entrapment. Thus, we suggest that coercive control is a motivating factor for some, but not all men who perpetrate reproductive coercion and abuse. A greater understanding perpetrator motivations may be important for practitioners, particularly those working in sexual and reproductive health services, since it could be relevant to women’s level of risk for coercive controlling behaviour or more extreme forms of physical or sexual violence.

The increase in fungal infections, accompanied by adverse effects and acquired resistance associated with the use of antifungal agents used for their clinical management, have facilitated the search for new substances with antifungal properties. Naphthoquinones have been investigated due to their multiple biological activities, including their significant antifungal potential. This study aimed at evaluating the antifungal potential of naphthoquinones against opportunistic fungi and dermatophytes and to assess the impact of a selected naphthoquinone on the formation of the cell wall, ergosterol membrane, and cellular membrane of Candida albicans ATCC 60193. Additionally, cytotoxicity in the MRC-(Medical Research Council-)5 cell lineage, Artemia salina, and tomato as well as arugula seeds was evaluated. The antifungal activity of four naphthoquinones was assessed using well-characterized fungal strains, the minimum inhibitory concentration (MIC) was determined applying the microdilution assay technique. Antifungal activity of the assessed naphthoquinones could be confirmed, particularly for 2,3-DBNQ (2,3-dibromo-1,4-naphthoquinone), which showed prominent antifungal activity (MIC of &lt;1.56 - 6.25 µg/mL) in all chosen test settings. However, its toxicity in MRC-5 cells (IC50 = 15.44 µM), a recorded 100% mortality in A. salina at a concentration of 50 µg/mL, as well as inhibition of 94.8% of the tomato seeds at a concentration of 400 µg/mL and inhibition of 64.1% of arugula seeds at a concentration of 200 µg/mL may limit hypothetical therapeutic applications. It was demonstrated that the likely mechanism of action of 2,3-DBNQ involves interfering with fungal membrane permeability, leading to increased leakage of nucleotides. This study adds to available knowledge on antifungal effects of naphthoquinones, especially of 2,3-DBNQ, against opportunistic yeasts and dermatophytes. However, the observed cytotoxicity in the MRC-5 cell lineage, A. salina, as well as tomato and arugula seeds highlights a need for further research to optimize the selectivity and safety profile of naphthoquinones like 2,3-DBNQ before potential clinical use may be assessed.

The cork oak (Quercus suber L.), endemic essence of the Mediterranean Basin, is commonly used in traditional pharmacopoeia. The main objective of this work is to enhance the valorization of this plant species through the study of the anticandidosic activity of cork oak bark methalonic extracts in order to develop an efficient natural formulation for Candidiasis treatment.The anticandidosic activity of methanolic extracts of Q. suber bark stemming from decoction, maceration and Soxhlet methods of extraction in was tested on five different Candida albicans strains. Our results showed that all the tested extracts displayed an inhibitive activity, which varies according to the obtained extract and the tested strain. The best anticandidosic potential was observed with extracts obtained with Soxhlet method. The study of the acute toxicity showed that the lethal dose is 1150 mg/kg in mice, which remained moderately toxic according to Hodge and Sterner classification scale. Thus, this extract can be used in phytotherapy without danger in doses that are below 300 mg/kg of corporal weight. Based on these results, we can conclude that Cork oak bark extracts can be used to treat Candida albicans infections.

Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding, blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

Assessment of drugs toxicity and associated biomarker genes is one of the most important tasks in the pre-clinical phase of drug development pipeline as well as in the toxicogenomic studies. There are few statistical methods for the assessment of doses of drugs (DDs) toxicity and their associated biomarker genes. However, these methods consume more time for computation of the model parameters using the EM (Expectation-Maximization) based iterative approaches. To overcome this problem, in this paper, an attempt is made to propose an alternative approach based on hierarchical clustering (HC) for the same purpose. There are several types of HC approaches whose performance depends on different similarity/distance measures. Therefore, we explored suitable combinations of distance measures and HC methods based on Japanese Toxicogenomics Project (TGP) datasets for better clustering/co-clustering between DDs and genes as well as to detect toxic DDs and their associated biomarker genes. We observed that Word’s HC method with each of Euclidean, Manhattan and Minkowski distance measures produces better clustering/co-clustering results. For an example, in case of glutathione metabolism pathway (GMP) dataset LOC100359539/Rrm2, Gpx6, RGD1562107, Gstm4, Gstm3, G6pd, Gsta5, Gclc, Mgst2, Gsr, Gpx2, Gclm, Gstp1, LOC100912604/Srm, Gstm4, Odc1, Gsr, Gss are the biomarker genes and Acetaminophen_Middle, Acetaminophen_High, Methapyrilene_High, Nitrofurazone_High, Nitrofurazone_Middle, Isoniazid_Middle, Isoniazid_High are their regulatory (associated) DDs explored by our proposed co-clustering algorithm based on the distance and HC method combination Euclidean: Word. Similarly, for the PPAR signaling pathway (PPAR-SP) dataset Cpt1a, Cyp8b1, Cyp4a3, Ehhadh, Plin5, Plin2, Fabp3, Me1, Fabp5, LOC100910385, Cpt2, Acaa1a, Cyp4a1, LOC100365047, Cpt1a, LOC100365047, Angptl4, Aqp7, Cpt1c, Cpt1b, Me1 are the biomarker genes and Aspirin_Low, Aspirin_Middle, Aspirin_High, Benzbromarone_Middle, Benzbromarone_High, Clofibrate_Middle, Clofibrate_High, WY14643_Low, WY14643_High, WY14643_Middle, Gemfibrozil_Middle, Gemfibrozil_High are their regulatory DDs. These results are validated by the available literature and functional annotation.

RNA extraction from human cumulus cells (CCs) is considered challenging due to low cell’s pop-ulation and small cell. The successful gene expression analysis from cumulus cells ultimately de-pends on an excellent concentration of Ribonucleic acid (RNA) yield by an appropriate technique. Our study aims to consolidate appropriate cumulus cell collection method, preparation and ex-traction techniques to ensure a good yield of RNA for better gene expression analysis. From the results obtained, the optimal strategy found involved mechanical denudation without an enzy-matic process, followed by the use of RNA stabilizer prior to RNA extraction. Subsequently, uti-lizing a smaller homogenizer, preferably manual pressure control with filter (Bio-Masher III®) is paramount for a pure and homogenize sample. Subsequently, during RNA extraction, the use of RNeasy micro kit and RNA carriers is recommended. These sample collection, preparation, and extraction techniques yielded an excellent-quality RNA concentration and successful gene expres-sion analysis. We also conducted a systematic review to consolidate our findings with current evidence of RNA extraction technique. Our results added a value as a current strategy for opti-mizing RNA extraction in CCs for experimental studies. Thus, our findings can contribute to for-mulating a better strategy for optimizing the RNA extraction in CCs for transcriptomic studies.

The giant anteater (Myrmecophaga tridactyla) is a vulnerable specie from Central and South America and is considered extinct in Belize, Guatemala, El Salvador, and Uruguay. Therefore, studies describing the reproductive characteristics of this species are pivotal for its conservation. Thus, this study aimed to provide a morphological description of their female reproductive tissues. We collected tissue samples from six female giant anteaters, and performed gross, morphological, and histochemical analyses. Five adult and one young subjects were enrolled in the study. In the ovary, classifications were made according to the follicle and oocyte sizes: primordial, primary, secondary, early antral, or antral. Typical follicles with a single oocyte surrounded by a simple or stratified layer of cubic epithelium, atretic follicles, corpora lutea, corpora albicans, and ovarian cysts were also observed. No ovarian lesions were observed. By contrast, endometritis, metritis, mucometra, and endometrial cysts were identified in the uterus. Uterine alterations in these subjects were frequent and could affect reproduction.

Introduction: Since its discovery in late 2019, the novel coronavirus (SARSCOVID-2) that causes COVID-19 has spread fast, prompting the World Health Organization (WHO) to designate the disease a worldwide pandemic on March 11, 2020.The epidemic has profoundly altered the preexisting global sexual and reproductive health landscape .The virus’s load has put ordinary services in jeopardy and harmed other health priorities. This encompasses both the provision and the supply of contraceptives, sexual health, new born and maternal health services. This Scoping review therefore mapped the availability evidence on the impact and effects of the COVID-19 disease outbreak on sexual and reproductive health. Methods: The methodological framework by Arksey and O’Malley guided this scoping review. A literature search was conducted from the following databases: Embase, PubMed, CINAHL, Scopus, WOS, and AJOL. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram and the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) checklist were used to document the review process. The Strobe critical review checklist was used to determine the quality of the included studies. Results:19 studies were reviewed, out of which 4 were cross sectional studies, 1 was an observational study, 1 was a descriptive analytical study and the rest were qualitative studies .Majority of the studies showed evidence on the impact of COVID-19 and family planning service, maternal and child services, and three studies reported on COVID-19 and sexual behaviour. Five of the nineteen included studies reported on the impact of COVID-19 and family planning service. Conclusion: This scoping review has granted the assessment of the impact of novel SARS-CoV-2 on Sexual and reproductive health services with regards to sexual behaviour, family planning and maternal, neonatal and child health. From the 18 articles identified and reviewed, the overall responses stipulated a significant reduction in client’s utilization of services due to challenges experiences in service implementation such as stock outs. In addition, low demand for reproductive health services by clients due to restrictions imposed on the movements of people to curb the spread of the virus. It is therefore important that Governments and relevant stakeholders in Maternal and Sexual Reproductive Health prioritize development of policies and practices that protect women from the impacts of the pandemic. Furthermore, regular audits to detect trends in MSRH are necessary to inform on going mitigation efforts.

Cadmium (Cd) is an environmental toxicant of worldwide public health significance. Diet is the main non-workplace Cd exposure source other than smoking. The intestinal absorption of Cd involves the transporters for iron, zinc, copper, and calcium. These metal transporters essentially determine the body burden of Cd because only 0.001-0.005% of Cd accumulated in the body can be excreted in urine each day. The International Agency for Research on Cancer listed Cd as a human lung carcinogen. Current evidence, however, suggests that environmental Cd may increase the prevalence of many types of cancer, notably lung, liver, breast, pancreas, and kidney. A two-year bioassay that mimics a lifelong exposure demonstrates Cd caused neoplasms in multiple tissues of mice. Also, several non-tumorigenic human cell lines underwent malignant cell transformation, when they were exposed to a sublethal dose of Cd for a prolonged time. Cd does not directly damage DNA, but it can profoundly affect gene expression through its interactions with various proteins, and Cd can thus be viewed as a transcription modulator. The present review highlights epidemiological studies that connected an enhanced risk of various neoplastic diseases to chronic exposure to environmental Cd. Special emphasis is on the impact of body iron stores on the absorption rate of Cd, and its implications for breast cancer prevention in highly susceptible subpopulation groups of women. Resistance to cell death and other cancer phenotypes acquired during Cd-induced cancer-cell transformation, under in vitro conditions, are briefly discussed. The potential role for ZnT1 efflux transporter in cellular acquisition of tolerance to Cd cytotoxicity are highlighted.

The intestinal microbiota, comprised of bacteria, archaea, and phages, inhabits the gastrointestinal tract of the organism. Male reproductive sterility is currently a prominent topic in medical research. Increasing research suggests that gut microbiota dysbiosis can result in various reproductive health problems. This article specifically investigates the impact of gut microbiota dysbiosis on male reproductive infertility development. Gut microbiota imbalances can disrupt the immune system and immune cell metabolism, affecting testicular growth and sperm production. This dysfunction can compromise the levels of hormones produced and secreted by the endocrine glands, affecting male reproductive health. Furthermore, imbalance of the gut microbiota can disrupt the gut-brain-reproductive axis, resulting in male reproductive infertility. This article will explore how the imbalance of the gut microbiota impacts male reproductive infertility through immune regulation, endocrine regulation, and interactions of the gut-brain-reproductive axis, concluding with recommendations for prevention and treatment.

Obesogens have been identified as a significant factor associated with increasing obesity rates, particularly in developed countries. These substances with obesogenic traits are prevalent in consumer products, including certain pharmaceuticals. Specific classes of pharmaceuticals have been recognized for their ability to induce weight gain, often accompanied by hormonal alterations that can adversely impact male fertility. Indeed, research has supplied evidence underscoring the crucial role of obesogens and therapeutic agents in the normal functioning of the male reproductive system. Notably, sperm count, and various semen parameters have been closely linked to a range of environmental and nutritional factors, including chemicals and pharmacological agents exhibiting obesogenic properties. This review aims to explore studies focused on analyzing male fertility parameters, delving into the intricacies of sperm quality, and elucidating the direct and adverse effects that pharmacological agents may have on these aspects.

Rat is one of the most commonly used model animals for biological research. The organs and systems of human being are somewhat similar to that of rat in structure as well as functions, making it a valuable choice for research experimentation in biological sciences. A number of studies have been conducted to evaluate the potential risks and toxicity of different elements on the physiology and histology of rats. There is need to address certain environmental factors affecting rats condition during experimentation. Reproduction along with its pathologies is under investigation on larger scale throughout the world, being central for the existence of a species. These studies focus on the major factors that influence reproductive function. Review of literature clearly indicated the unwanted consequences of over nutrition, malnutrition, high or low temperature, non-enriched housing, improper handling, intense or poor light exposure and environmental pollution on histology and hormonal profile of reproductive system of rats.

To explore the effects of pymetrozine on the reproductive behavior of N. lugens, we established a bioassay method to accurately evaluate the toxicity of pymetrozine in N. lugens and establish the level of pymetrozine resistance of N. lugens in the field. In this study, pymetrozine’s effects on the fecundity of N. lugens were evaluated using the topical application method and rice-seedling dipping method. Moreover, the resistance of N. lugens to pymetrozine in a pymetrozine-resistant strain (Pym-R) and two field populations (YZ21 and QS21) was determined using the rice-seedling dipping method and fecundity assay methods. The results showed that treatment of N. lugens third-instar nymphs with LC15, LC50, and LC85 doses of pymetrozine resulted in significantly reduced male fertility and female fecundity. In addition, N. lugens adults treated with pymetrozine using the rice-seedling dipping and topical application method also exhibited significantly in-hibited male courtship, fertility, and female receptivity. Using the rice-stem dipping method, pymetrozine resistance was shown to be at high levels in Pym-R (194.6-fold), YZ21 (205.9-fold), and QS21 (212.8-fold), with LC50 values of 522.520 mg/L (Pym-R), 552.962 mg/L (YZ21), and 571.315 (QS21) mg/L. However, when using the rice-seedling dipping or topical application fe-cundity assay method, Pym-R (EC50: 14.370 mg/L, RR=12.4-fold; ED50: 0.560 ng/adult, RR=10.8-fold), YZ21 (EC50: 12.890 mg/L, RR=11.2-fold; ED50: 0.280 ng/adult; RR=5.4-fold), and QS21 (EC50: 13.70 mg/L, RR=11.9-fold) exhibited moderate or low levels of resistance to pymet-rozine. Our studies show that pymetrozine can significantly inhibit the fecundity of N. lugens. The fecundity assay results showed that N. lugens only developed low to moderate levels of resistance to pymetrozine, indicating that pymetrozine can still achieve effective control on the next gen-eration of N. lugens populations.

African swine fever (ASF) has evolved from an exotic animal disease to a threat to global pig production. An important avenue for wide-spread transmission of animal diseases is the dissemination of viruses through boar semen used for artificial insemination (AI). In this context, we investigated the role of male reproductive organs in ASF. Mature domestic boars and adolescent wild boar inoculated with different ASF virus strains were investigated by means of virological and pathological methods. Additionally, electron microscopy was employed to investigate in vitro inoculated sperm. Viral genome, antigen and infectious virus could be found in all gonadal tissues and accessory sex glands. The viral antigen and viral mRNAs were mainly found in mononuclear cells of the respective tissues. However, some other cell types, including Leydig, endothelial and stromal cells were also found positive. Using RNAScope, p72 mRNA could be found in scattered halo cells of the epididymal duct epithelium which could point to disruption of the barrier. No direct infection of spermatozoa was observed by immunohistochemistry or electron microscopy. Taken together, our results strengthen the assumption that ASFV can be transmitted via boar semen. Future studies are needed to explore excretion dynamics and transmission efficiency.

The rise of data science in biology stimulates interdisciplinary collaborations to address fundamental questions. Here, we report the outcome of the first SINFONIA symposium focused on revealing the mechanisms governing plant reproductive development across biological scales. The intricate and dynamic target networks of known regulators of flower development remain poorly understood. To analyze development from the genome to the final floral organ morphology, high-resolution data that capture spatiotemporal regulatory activities are necessary and require advanced computational methods for analysis and modeling. Moreover, frameworks to share data, practices and approaches that facilitate the combination of varied expertise to advance the field are called for. Training young researchers in interdisciplinary approaches and science communication offers the opportunity to establish a collaborative mindset to shape future research.

The Pygmy hog (Porcula Salvania), till recently, classified as a critically endangered suid, is facing the threat of extinction globally due to habitat degradation. Efforts are being made to protect the pygmy hogs from extinction and breed them in captivity under Pygmy Hog Conservation Pro-gramme (PHCP). However, very little information is available on the reproductive physiology of pygmy hogs. Therefore, the present study aimed to standardize enzyme immunoassays (EIAs) for monitoring pregnancy and reproductive status using progesterone and testosterone metabolites. A total of 785 faecal samples were collected from five females and two males over a period of one year from PHCP Research and Breeding Centre, Guwahati, Assam. High-pressure liquid chro-matography (HPLC) analysis revealed the presence of immunoreactive progesterone and testos-terone metabolites in faeces. Mating was observed in all the five females and four of them gave birth successfully. We were able to detect pregnancy using faecal progesterone metabolites. Based on mating and parturition, the mean gestation period was estimated to be 153.25 days from four females. The breeding centre recorded 172 births between 1996 and 2000 and found strong sea-sonality in births and most of the births were between May and June. Faecal testosterone metabo-lites were significantly higher in the breeding season than the non-breeding season. This is the first study and will help in future breeding programs in other captive breeding centres and reproduc-tive monitoring of reintroduced populations.

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role, and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.

Persistent Organic Pollutants (POP) such as dichlorodimethyltrichloroethane (DDT) are present and ubiquitous in the environment due to their resilient nature. DDT is a prevalent endocrine disruptor still found in detectable amounts in organisms and the environment even after its use was banned in the 1970s. Studies show that exposure to DDT can cause adverse health effects in humans and animals, impairing fertility and increasing the risk of developing cancer. The aim of this work is to provide a comprehensive overview of the available literature on the effect of DDT and its metabolites on female reproductive tract, leading to infertility and cancer. Medline and Google Scholar were systematically searched to detect all relevant animal and human studies published in the last 20 years (January 2003 to February 2023) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 38 studies were included for qualitative synthesis. This systematic search and review indicated that exposure to DDT is associated with female reproductive health decline and that DDT acts as a sufficient carcinogen instigating reproductive cancers.

Heavy load carrying of water, firewood, and sand/stones is a ubiquitous activity for women living in developing countries. Although the intra-abdominal pressure associated with heavy load carrying is hypothesized to increase the risk of pelvic organ prolapse (POP) among women, relevant epidemiologic data are lacking. We conducted a comparative study involving two exploratory cross-sectional studies among convenience samples of women carrying heavy loads, with different characteristics: (1) as part of their activities for daily living, in Shinyanga region, Tanzania; and (2) working as sand miners in Pokhara, Nepal. Women were categorized has having “low” or “high” load-carrying exposures based on the measured weights of the loads being carried at the time of the survey, as well as on self-reported duration and frequency of load carrying. A summary score for lower abdominal discomfort suggestive of POP was generated using questions from the Pelvic Organ Prolapse Distress Inventory (POPDI-6). Women with higher load carrying exposures had on average higher discomfort scores in both Tanzania (adjusted prevalence difference (PDa)=3.7; 95% CI: -3.8-11.3; p=0.33) and Nepal (PDa=9.3; 95% CI: -4.9-23.6; p=0.18). We identified trends suggestive of an association between increasing heavy load carrying exposures and symptoms of lower abdominal discomfort. Our findings underscore the need for larger epidemiologic studies of the potential adverse reproductive health effects of heavy load carrying activities on women in developing countries.

Inflammation is a cause of number of disorders. Many anti-inflammatory drugs are available to cure and prevent inflammation and its related disorders. Some of the drugs are from plant and animal origin. Among animals snake venom is also utilized as treatment option of certain disorders. In the current study the venom of N. oxiana from Northern areas of Pakistan is assayed to determine its anti-inflammatory activity. The Naja oxiana is also called central Asian cobra is endemic to Central Asia. Naja oxiana belong to family Elapidae and it is highly venomous snake. The venom has many enzymatic proteins as well as nonenzymatic proteins that is neurotoxins. The venom is lethal having very high mortality rate and the death may occur due to respiratory failure in 45 minutes to 24 hrs depending upon the nature and amount of venom. As the venom is highly toxic so initially after venom milking its protein estimation was done and toxicity profile and LD50 was determined to find out its therapeutic dose at which anti-inflammatory activity was observed. The toxicity and anti-inflammatory activity was determined on mice model. Inflammation was induced by carrageenan induced peritonitis method. The inflammatory markers ROS, TNF-α and IL-β were determined by ELIZA in peritoneal fluid. The LD50 of crude venom, fraction 1 and fraction 2 was found as 34 µg/kg, 7.4 µg/kg and 416 µg/kg respectively. Anti-inflammatory activity crude venom, fraction 1 and fraction 2 was found at dose 19 µg/kg, 1.8 µg/kg and 267 µg/kg respectively. The levels of inflammatory markers reduced after therapeutic dose administration of venom and its fractions that indicates that it can be utilized as anti-inflammatory agent and so can be effective in various disorders.

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second-largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter in monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protected transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from the infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and Toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. PK parameters at those high doses were proportional to the dose, with the half-life in serum of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue Cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with tissues of these species, supporting the PK/Tox results in vivo and suggesting that while IgG-A7 has a broad efficacy profile it is not toxic in humans. The information generated in CD-1 mouse as PK/Tox model, complemented with the mouse and human TCR, could be of relevance as alternatives to NHPs in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.

Alginate extraction is from seaweed, and lignin separation is from by-product corn (stalks and leaves). Alginate/lignin is a synthetic polymer rich in biological activity of great interest. Antioxidant activities of alginate/lignin were evaluated, such as total antioxidant activity, reducing power activity, DPPH free radical scavenging activity, and α – glucosidase inhibition activity. The test of anticancer activity was on four cell lines (Hep G2, fibroblast, MCF-7, and NCI H460). Determination of physical-chemistry characteristics of alginate/lignin was through FTIR, DSC, SEM_EDS, SEM_EDS mapping, XRD, XRF, and 1H-NMR. A study of acute toxicity of alginate/lignin was on Swiss albino mice. The results showed alginate/lignin possessed antioxidant activity such as total antioxidant activity, reducing power activity, especially, α – glucosidase inhibition activity, and no free radical scavenging activity. Alginate/lignin did not be typical in cancer cell lines. Alginate/lignin existed in a thermally stable regular spherical shape in the investigated thermal region. Some specific functional groups of alginate and lignin did not exist in alginate/lignin crystal. Elements such as C, O, Na, and S were popular in the alginate/lignin structure. LD0 and LD100 of alginate/lignin in mice were 3.91 g/kg and 9.77 g/kg, respectively. Alginate/lignin is the potential for application as pharmaceutical materials, functional foods, and supporting diabetes treatment.

This work is related to the environmental toxicology risk assessment and evaluation of possible transformation of carbon-based nanomaterials (CNMs) after the contact with marine microalgae. The materials used in the study represent common and widely applied multiwalled carbon nanotubes (CNTs), fullerene (C60), graphene (Gr), and graphene oxide (GrO). The toxicity was evaluated as growth rate inhibition, esterase activity, membrane potential, and reactive oxygen species generation changes. The measurement was performed with flow cytometry after 3, 24, 96 h, and 7 days. Biotransformation of nanomaterials were evaluated after 7 days of microalgae cultivation with CNMs by FTIR and Raman spectroscopy. The calculated toxic level (EC50 in mg/L, 96 h) of ued CNMs reduced in the following order: CNTs (18.98) &gt; GrO (76.77) &gt; Gr (159.40) &gt; C60 (414.0). Oxidative stress and membrane depolarization was the main toxic action of CNTs and GrO. At the same time, Gr and C60 decreased the toxic action with time and had no negative impact on microalgae even at concentration of 125 mg/L. Moreover, C60 and Gr after seven days of the contact with microalgae cells obtained structural deformations.

Introduction: Oral Nicotine Pouches (ONPs) are the new form of nicotine pouches that have become a type of emerging smokeless tobacco product sold by various tobacco companies. These smokeless tobacco products are being marketed for usage all over as Snus containing tobacco-derived nicotine (Natural) or as tobacco-free nicotine (Synthetic) as substitutes for other tobacco products that are limited in public places. ONPs have become popular tobacco products among adolescents/young adults and over 50% of young adult users of ONP use flavored ONP, such as menthol/mint, tobacco, dessert/candy, and fruity, being the most popular flavors. Various new ONP flavors are currently popular locally as well in the online market. Tobacco, Menthol, and fruit-flavored ONPs could motivate cigarette smokers to alteration to ONPs. Methods: We expanded our knowledge on natural/synthetic ONP flavors wheels to available data on ONPs, describing in detail their flavors and brands (US and Europe) in both natural/Synthetic ONP categories. We classified over 152 snus and 228 synthetic ONPs into the following flavor categories: “Tobacco”, “Menthol/Mint”, “Fruity”, “Candy/Deserts”, “Drink”, “Aroma”, “Spices” and “Mixed Flavors”. Results: Based on total numbers, wefound that the most popular ONPs flavor sold as tobacco and menthol to be among natural ONPs, among synthetic ONPs fruity and menthol as the most prominent flavors with varying concentrations of nicotine and other flavoring chemicals including coolant WS-23. We also illustrated possible molecular targets and toxicities due to exposure to ONPs activating several signaling cascades like AKT and NF-B might possibly lead to apoptosis and epithelial mesenchymal transition (EMT). Conclusions: Considering the marketing of ONP products with various flavor profiles and most of these products containing tobacco/menthol/fruit flavor, it is likely to have regulation and marketing disclaimer on some of these products. Further, it would be logical to determine how the market reacts in terms of compliance and non-compliance with flavor restrictions by the regulatory agencies.

This review article seeks to provide relevant information about the applicability of cell-based assays in assessing cytotoxicity of phytochemicals in light of several traditional methods available. Phenolic compounds and other phytochemicals are significant resources for drug discovery and development, thus underlining the enormous potentials of plant-derived natural products for the prevention and management of oxidative stress associated with cancer and other diseases. These effects have been linked to the content of phytochemicals such as phenolic compounds and their antioxidant properties. The abundance and complexity of these bio-constituents highlight the need for well-defined methods for the in vitro characterization and quantification of extracts and/or preparations that can translate to in vivo effects. Cell culture systems provide a useful model for basic research and a wide range of clinical in vitro studies and physiological processes as well as assessing the toxicity and therapeutic potential of compounds including plant extracts with potential medicinal benefits. Their use in cancer research provide a useful insight into possible therapeutic properties of phytochemicals at the cellular level. This approach has been instrumental in the initial stages of developing chemotherapeutic agents where human cancer cell lines are used as experimental models. These models have continued to contribute to elucidating specific requirements for certain biochemical events associated with proliferation, metabolism, loss of cell viability/apoptosis. Cell culture systems remain a promising tool in natural product development.

Migratory movements are a political, social and public health issue on a global scale. Access to sexual and reproductive health services for irregular migrant women (IMW) is a public health issue. The aim of this study is to identify qualitative evidence on IMW's experiences of sexual and reproductive health care in emergency and primary care settings. Methods: meta-synthesis of qualitative studies. Synthesis includes assembling and categorising findings based on the simili-arty in meaning. The search was conducted between January 2010 and June 2022 using PubMed, WOS and CINAHL databases. Results: of 131 articles found in the initial search, only 9 articles met the criteria and were included in the review. Four main themes were established: (1) The need to focus emergency care on sexual and reproductive health, (2) Unsatisfactory clinical experiences, (3) Forced reproduction, (4) Alternating between formal and informal healthcare services. Con-clusions: IMW’s attitudes towards sexual and reproductive health are influenced by culture, ed-ucational level, fear, barriers and the attitude of healthcare providers. Healthcare institutions need to be aware of the IMW’s experiences to understand the specific difficulties they face. IMW call for socially and culturally sensitive health care, cultural mediators, improved communication and safe environments that ensure confidentiality.

The corpus luteum is a temporary reproductive endocrine structure established from a ruptured follicle wall after ovulation. In the ovarian cycle of ruminant species, the corpus luteum organ undergoes a repeated pattern of specific cellular proliferation, differentiation, and transformation. The corpus luteum encounters several physiological events, including growth, function, and regression throughout its life span. Also, the corpus luteum comprises granulosa and theca cells and endothelial cells, such as luteal steroidogenic cells and luteal endothelial cells. These cells play an important role in the physiology of the corpus luteum and the maintenance and degeneration of the corpus luteum. Furthermore, the role of reproductive hormones in the ovaries is important. Representative hormones include estrogen, progesterone, prostaglandin F2α, and oxytocin. Understanding their functions is important in studying the physiological phenomena and various mechanisms of the corpus luteum in the ovary. Therefore, the following review will discuss the role of reproductive hormones and luteal cell types in the microenvironment of the corpus luteum in the bovine ovary.

Sperm marking represents a valuable monitoring tool for genetic pest control strategies such as the Sterile Insect Technique, but also provides a key tool for reproductive biology studies. Sperm-marked lines can be generated by introducing transgenes that mediate the expression of fluorescent proteins during spermatogenesis. Homozygous lines established by transgenesis approaches are going through a genetic bottleneck that can lead to reduced fitness. Transgenic SIT approaches have mostly focused on Dipteran and Lepidopteran pests so far. With this study, we provide sperm-marked lines for the Coleopteran pest model organism, the red flour beetle Tribolium castaneum, based on the β2-tubulin promoter/enhancer driving red (DsRed) or green (EGFP) fluorescence. The obtained lines are reasonably competitive and were thus used for studies on reproductive biology confriming the phenomenon of ‘last male sperm precedence’ and that the spermathecae are deployed for long term sperm storage enabling the use of sperm from first matings even after secondary matings for a long period of time. The homozygosity and competiveness of the lines will enable future studies to analyze the controlled process of sperm movement into the long time storage organ as part of a post-mating cryptic female choice mechanism of this extremely promiscuous species.

The manuscript presents the comprehensive integrative theory of the etiology and pathogenesis of Alzheimer’s disease - the amyloid degradation toxicity hypothesis - and describes the logic that underlies it.The analysis of amyloid biomarkers and stable-isotope label kinetics (SILK) studies suggest that AD diagnosis is associated with higher cellular uptake of beta-amyloid. Uptake of beta-amyloid by cells is needed for its cytotoxicity, so the uptake rate should correlate with the rate of neurodegeneration. Also, the initial step in forming extracellular aggregates cannot occur in the interstitial fluid due to the extremely low concentration of beta-amyloid but can occur intralysosomally. Therefore, the density of extracellular aggregates should positively correlate with the rate of cellular amyloid uptake. The model, which considers that both cytotoxicity and aggregation of beta-amyloid are defined by cellular uptake, successfully reproduces the probability distribution of AD diagnosis in the population. Cellular uptake of beta-amyloid is mediated by endocytosis. Endocytosed beta-amyloid induces lysosomal permeabilization that occurs without plasma membrane damage. Lysosomal permeabilization explains ion disturbances, such as an accumulation of intracellular calcium, caused by cell exposure to extracellular beta-amyloid. Some amyloid fragments, produced from beta-amyloid by lysosomal proteases, can form membrane channels in lysosomal membranes, which are large enough to leak cathepsins to the cytoplasm. Appearance of proteases in the cytoplasm results in necrosis and/or initiation of apoptosis. If the cell survives, the damage of lysosomes leads to autophagy failure and slow recycling of mitochondria, promoting the production of reactive oxygen species and potentiating cell damage.Considering the above, the integrative theory of AD etiology and pathogenesis can be formulated. The etiology of AD is the membrane channel formation by amyloid fragments produced in lysosomes. The pathogenesis includes lysosomal permeabilization by giant membrane channels, which leak lysosomal proteases into the cytoplasm. The correlation between the density of amyloid aggregates and the probability of AD appears because the intensity of cellular uptake defines both aggregation rates in vivo and cytotoxicity of beta-amyloid.The amyloid degradation toxicity hypothesis is the integrative theory of Alzheimer’s disease (AD). It successfully interprets multiple phenomena and paradoxes associated with AD pathobiology at various levels, from molecular and cellular to biomarkers. The hypothesis explains the limitations of currently used biomarkers of AD and proposes etiology-related parameters. These parameters could be measured in humans and become novel diagnostic and prognostic clinical tools. Based on the proposed framework, we foresee the development of effective medications to treat, stall the progression of, or prevent disease development.

The widespread use of the herbicide glyphosate has resulted in the global presence of its degra-dation product, aminomethylphosphonic acid (AMPA), in the global environment. AMPA is commonly found in water bodies, including freshwater systems. We investigated the effects of chronic and acute AMPA exposure on the survivorship, regenerative abilities, and locomotion of the brown planarian (Girardia tigrina), a water-dwelling flatworm commonly found in freshwa-ter ecosystems. We exposed planarians to two concentrations of AMPA, consistent with the high and low ranges of concentrations observed in US water systems. We measured endpoints includ-ing survivorship, regenerative abilities of head and tail segments, eyespot regeneration, and swimming speed. Compared to the control group, we found that planarians chronically exposed to AMPA exhibited (1) modestly reduced survivorship while regenerating and (2) slower regen-eration from the tail segment. No significant differences were observed in intact body growth during chronic exposure. Our findings highlight the potential ecological impacts of AMPA con-tamination on planarian populations. Understanding the effects of AMPA exposure on planarians contributes to our understanding of the ecological consequences of glyphosate use in freshwater ecosystems.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2 (Palrasu et al., 2019). Given lack of knowledge about side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50mg/kg/day via subcutaneous injections and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the mice body weight, blood cell count, blood chemistry, or organs following the compound treatment. The results show that our compounds 2155-14 and 2155-18 are not toxic for the study period of three weeks.

The creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylamino)(phenyl) phosphonium iodides (bromides) 1 containing one, two, or three diethylamino groups were obtained by the reaction of alkyl iodides (bromides) with (diethylamino)(phenyl)phosphines under mild conditions and high yields. The structure of compounds 1 was established by NMR and XRD. In vitro a high cytotoxicity against the lines M-Hela, HuTu 80, PC3, DU-145, PANC-1 and MCF-7 was found. Selectivity index are in the range of 0.06-4.0 M (SI 17-277) for the most active compounds. ROS production, mitochondrial localization and the process of cellular apoptosis were investigated. Decorated by 1 of lipid systems (liposomes and solid lipid nanoparticles) improve the cytotoxicity and a decrease in toxicity against normal cell lines. Compounds 1 induce apoptosis proceeding along the mitochondrial pathway. Aminophosphonium salts 1 also exhibit a high selective activity against the Gram-positive bacteria strains S. aureus 209P, B. segeus 8035, including methicillin-resistant strains of S. aureus (MRSA-1, MRSA-2), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead compounds.

Objective: The study aimed to explore the experiences of women undergoing Assisted Reproductive Technologies namely; Invitro Fertilization and Intracytoplasmic Sperm Injection at the Finney Hospital and Fertility Centre, New Bortianor, Ghana. Method: A qualitative research design was employed to analyse and describe the experiences of the women seeking Assisted Reproductive Technologies. Fifteen women were invited and interviewed using a semi-structured interview guide. The responses were transcribed verbatim and analysed using content analysis. Results: Three themes emerged from the study: the women’s experiences, challenges and the roles and contributions of significant others. The women were anxious, stressed-up, exhausted and financially burdened. Spouses and health professionals played significant roles by providing social, emotional and financial support for these women. Significant others such as spouses and close relatives were supportive and provided encouragement to the women. Conclusion: The experiences of women undergoing Assisted Reproductive Technologies are multi-dimensional. Thus psychosocial intervention as part of ART services with health insurance cover may be client-centered and more appropriate for these group of women.

A novel and highly pathogenic coronavirus (2019-nCoV)-induced pneumonia spread worldwide in a short time. However, studies on the effects of 2019-nCoV on the male reproductive system are limited. The aim of this study is to describe the clinical characteristics of the male reproductive system of COVID-19 patients and to explore the presence of 2019-nCoV in semen. Retrospective, single-center case series of 112 male patients with confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 2 to March 7, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. 2019-nCoV RNA measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on The Human Protein Atlas portal and investigated immunohistochemistry (IHC) images of the testis. The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in the testis. A total of 3 severe COVID-19 patients (2.7%) presented with orchidoptosis, while no patients experienced other symptoms or signs related to the male reproductive system. The analysis of 2019-nCoV RNA in semen included 17 patients with fertility needs. Among these patients, 9 (52.9%) remained positive for 2019-nCoV according to throat swab analysis, and 8 (47.1%) became negative. In the semen 2019-nCoV analysis, all 17 patients were negative for the N gene and ORF1ab gene. In view of the potential impairment, long-term follow-up for male COVID-19 patients with fertility needs is of great significance.

Understanding the reproductive patterns and strategies of a species is an important step in establishing the species’ life history. Campostoma oligolepis, the Largescale Stoneroller, is a species that has received little attention in the 90 years since it was first identified, and the work that has been done has been localized in the American Midwest. Collections of C. oligolepis were made monthly from the Flint River in Madison County in northern Alabama, USA, from March, 2014, to September, 2015. A total of 768 fish were collected over the collection period including 492 adults, 268 females and 224 males. We found strong evidence that the peak spawning time for C. oligolepis in the Flint River is March and April. Ovarian maturation, gonadosomatic index for both sexes, and monthly clutch size all support this conclusion. Two unexpected features were found. The first is how few females of mature size were found to carry either oocytes or a clutch except in the peak observed reproductive month of April, 2014. The second unusual feature is the prevalence of asymmetric ovaries, with the left the larger if a difference exists. Campostoma oligolepis may have unusually strong inter-annual responses to abiotic factors such as water temperature and river discharge.

For the first time, this study identified seven potential ligands with high binding energies through the docking approach against the Crystal Structure of human Melanoma-associated antigen B1 (MAGEB1). The ligands—Imatinib, Bafatinib, Diosmin, Ginkgetin, Bilobetin, Amentoflavone, and Hypericin—showing strong binding energies around -10 kcal/mol, indicate a potentially robust interaction with the target protein. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of these ligands. From these results, the parameters for Diosmin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile, making it a potential candidate for further consideration against Melanoma. Moving forward, it's advisable to conduct further experimental validations, including in vitro and in vivo studies, to confirm the efficacy and safety of Diosmin and other potential ligands. Consideration of pharmacokinetics, metabolism, and specific mechanisms of action will contribute to a comprehensive understanding of these compounds' potential as therapeutic agents.

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female WT mice were treated with Paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones including estrogen. RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by Paclitaxel but reversed the cardioprotection was observed in females after radiotherapy. Conversely, rhoB deficiency protected males from radiation toxicity. In sum, rhoB was identified as a molecular determinant driving estrogen dependent cardioprotection in female mice, whereas neuroprotection was not sex-hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

Streptococcus suis is a zoonotic pathogen causing serious infections in both swine and humans. Although metals are essential for life, excess amounts of metals they are toxic to bacteria. when accumulated in excess amounts. Except for zinc, Transcriptome-level data of the mechanisms for resistance to metal-induced toxicity in S. suis are available for no metals other than zinc. have not been investigated from the transcriptome level in S. suis. Herein, we explored the transcriptome-level changes of in S. suis in response to ferrous iron and cobalt toxicity by RNA sequencing. Many A lot of genes were differentially expressed in the presence of excess ferrous iron and cobalt. Most of the genes in response to cobalt toxicity showed the same expression trends as those were expressed in the same trend in response to ferrous iron toxicity. qRT-PCR analysis of the selected genes confirmed the accuracy of RNA sequencing results. Bioinformatics analysis of the differentially expressed genes indicated that ferrous iron and cobalt have similar impacts effects on the cellular processes of S. suis. Treatment with ferrous Ferrous iron treatment resulted in down-regulation of several oxidative stress tolerance-related genes involved in oxidative stress tolerance and up-regulation of the genes in an amino acid ABC transporter operon. Expression of the several genes in the arginine deiminase system was down-regulated in the presence of after ferrous iron and cobalt treatment. Collectively, our results suggested that S. suis alters the expression of a lot of multiple genes to respond to ferrous iron and cobalt toxicity.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

Recent studies have demonstrated an important role for vitamin C in the epigenetic regulation of cancer-related genes via DNA demethylation by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. DNA methyltransferase (DNMT) reverses this, increasing DNA methylation and decreasing gene expression. Dual oxidase (DUOX) enzymes produce hydrogen peroxide (H2O2) in normal pancreatic tissue but are silenced in pancreatic cancer (PDAC). Treatment of PDAC with pharmacologic ascorbate (P-AscH-, intravenous, high dose vitamin C) increases DUOX expression. We hypothesized that inhibiting DNMT may act synergistically with P-AscH- to further increase DUOX expression and cytotoxicity of PDAC. PDAC cells demonstrated dose-dependent increases in DUOX mRNA and protein expression when treated with DNMT inhibitors. PDAC cells treated with P-AscH- + DNMT inhibitors demonstrated increased DUOX expression, increased intracellular oxidation, and increased cytotoxicity in vitro and in vivo compared to either treatment alone. These findings suggest a potential therapeutic, epigenetic mechanism to treat PDAC.

Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English-language publications from 2008 – 2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimizing safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found few, but no serious, adverse events associated with phage therapy. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

Spherical or hexagonal NaYF4:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature coprecipitation and subsequently modified with three kinds of polymers. These included poly(ethylene glycol) (PEG) and poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] terminated with an alendronate anchoring group, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The internalization of nanoparticles by rat mesenchymal stem cells (rMSCs) and C6 cancer cells was visualized by electron microscopy and the cytotoxicity of the UCNPs and their leaches was measured by the real time proliferation assay. Comet assay was used to determine oxidative damage of UCNPs. In vivo study on mice determined the elimination route and potential accumulation of UCNPs in the body. The results showed that the L- and S-UCNPs were internalized into cells in the lumen of endosomes. Proliferation assay revealed that L-UCNPs were less toxic than S-UCNPs. The viability of rat mesenchymal stem cells (rMSCs) incubated with particles decreased in the order S-UCNP@Ale-(PDMA-AEA) > S-UCNP@Ale-PEG > S-UCNPs > S-UCNP@PMVEMA. Similar results were obtained in C6 cells. Oxidative damage measured by the Comet assay showed that neat L-UCNPs caused oxidative damage to rMSCs more than all coated UCNPs while no difference was observed in C6 cells. An in vivo study indicated that L-UCNPs were eliminated from the body via the hepatobiliary route; L-UCNP@Ale-PEG particles were almost eliminated from the liver 96 h after intravenous application. Pilot fluorescence imaging confirmed the limited in vivo detection capabilities of the nanoparticles.

In vitro fertilization (IVF) has revolutionized the field of assisted reproductive technologies (ART) by offering hope to individuals and couples struggling with infertility. Nevertheless, traditional IVF methods are not exempt from drawbacks, such as suboptimal success rates, intrusive procedures, and ethical considerations. The introduction of micro/nanorobotics in IVF offers a revolutionary chance to tackle these difficulties. This paper presents a short review of the utilization of micro/nanorobotics in IVF, investigating progress in the manipulation of sperm, retrieval of oocytes, culture of embryos, and potential future developments in this fast progressing area. In this discussion, we explore the fundamental concepts, advantages, difficulties, and possible influence of micro/nanorobotics in transforming IVF processes and enhancing patient outcomes.

Preconception or prenatal carrier screening for hereditary deafness is an effective early intervention strategy to reduce the incidence of newborn deafness, but current research is limited. This study aimed to investigate the carrier frequencies of common deafness genes in the Chinese population and to follow up on pregnancy outcomes in high-risk couples. Carrier screening for common deafness genes in the Chinese population, including the GJB2 and SLC26A4 genes, was performed using next-generation sequencing technology. Of the 9,993 subjects screened, the carrier rate was 2.86% for the GJB2 gene and 2.63% for the SLC26A4 gene. Of the six high-risk couples, four made alternative reproductive decisions (three with prenatal diagnosis and one with preimplantation genetic testing), with consequent successful termination of the birth of two affected fetuses. The frequencies of preconception or prenatal carrier screening for the deafness genes GJB2 and SLC26A4 in 9,993 subjects from China in this study were 2.86% and 2.63%, respectively. In addition, four out of six high-risk couples made alternative reproductive decisions, followed by the successful prevention of the birth of two affected fetuses. These findings confirmed the clinical utility of preconception or prenatal carrier screening for hereditary deafness.

Investigation of bacterial communities is on the rise both in human and veterinary medicine. Their role in health maintenance and pathogenic mechanisms is in the limelight of infectious, metabolic, and cancer research. Among the most considered, gut bacterial communities takes the cake. Their part in animals was assessed mainly to improve animal production, public health, and pet management. In this regard, canaries deserve attention, being a popular pet and source of economic income for bird-keepers, for whom breeding represents a pivotal point. Thus, the aim of the present work was to follow gut bacterial communities’ evolution along on whole reproductive cycle of 12 healthy female canaries. Feces were collected during parental care, molting, and resting phase, and submitted for 16S rRNA sequencing. Data analysis a substantial presence of Lactobacillus aviarius along all the phases, and a relevant shift of microbiota during molting and rest due to an abrupt decrease of Vermiphilaceae family. Although the meaning of such change is not clear, future research may highlight unforeseen scenarios. Moreover, Lactobacillus aviarius may be deemed for normal bacteria flora restoration in debilitated birds, perhaps improving their health and productivity.

Embryo quality evaluation during in vitro development is vital for the success of assisted reproductive technologies (ART). However, the subjective morphological assessment by embryologists may result in inconsistencies that affect the selection of the best embryo for transfer. To provide a more comprehensive evaluation of embryo quality, we performed the integration of embryo metabolomics with standardized morphokinetic classification. The culture medium of 55 embryos (from 21 couples undergoing ICSI) was collected at two timepoints (day 3 and 5). Samples were split into Good (n=29), Lagging (n=19) and Bad (n=10) according to embryo morphokinetic evaluation. Embryo metabolic performance was assessed by 1H-NMR, monitoring the variation of specific metabolites (pyruvate, lactate, alanine, glutamine, acetate, formate). Adjusted metabolite differentials were observed during the first three days of culture and found to be discriminative of embryo quality at the end of day 5. Pyruvate, alanine, glutamine, and acetate were major contributors to this discrimination. Good and Lagging embryos were found to export and accumulate pyruvate and glutamine in the 3 first days of culture, while Bad embryos consumed them. This suggests that Bad embryos have a less active metabolism than Good and Lagging embryos and these two metabolites as putative biomarkers for embryo quality. This study provides a more comprehensive evaluation of embryo quality and can lead to improvements in ART by enabling the selection of the best embryos. By combining morphological assessment and metabolomics, the selection of high-quality embryos with the potential to result in successful pregnancies may become more accurate and consistent.

Due to the influence of bio-geographical and environmental factors, as well as anthropogenic landscape features, organism shows different reproductive strategies among different populations. There is lack of detailed information on the reproductive biology of Kentish plover Charadrius al-exandrinus in arid lands in Central Asia. In this study, we summarized the characteristics of the reproductive biology of three geographically distinct plover populations in Aibi Lake in the Northwestern Xinjiang, Taitema Lake in the Southern Xinjiang and artificial reservoirs around Urumqi City in Northern Xinjiang respectively, based on 440 eggs of 158 nests observed and ana-lyzed from April to July of 2019 and 2020. We find that there is no significant difference in clutch size among the three populations. However, the egg size of Taitema Lake population is signifi-cantly larger than those of the other two populations, whilst egg volume and clutch volume of ar-tificial reservoirs population are significantly larger than that of Aibi Lake. With the postpone-ment of laying date, the northern and northwestern populations respectively show the character-istics of small clutch size and relatively small egg size, and decrease of reproductive outputs. The heavier female plovers in Taitema Lake lays eggs earlier, and there was significantly positive cor-relation between the female body mass and the clutch size and egg size. The tarsometatarsus length of the female plovers was significantly positively correlated with the reproductive output in all three populations. The model selection results show that female body size and ambient tem-perature restrict the egg size and reproductive output of Kentish plovers, which is consistent with the upper limit hypothesis of the maternal condition and the maternal constraint. Our data sup-port that Kentish plover show distinct flexibility in breeding strategies to cope with the harsh nat-ural environment in arid lands of Xinjiang, China. The results of relatively high average clutch size and average egg size imply that saline wetlands in Western China are important breeding habitats for Kentish plover.

Infertility affects approximately 15% of couples worldwide, an estimated 30% of which is related to male factor infertility. Application of low level laser therapy (LLLT) to improve fertility status is a rapidly growing discipline in medicine. Laser therapy triggers a variety of biological processes through interaction with primary cellular photoacceptors. The present review aims at evaluating the literature available in the MEDLINE/ PubMed on cellular and molecular mechanisms of photobiomodulation in the domains of reproductive and veterinary medicine. We primarily focused on the clinical application of laser treatment on seminal quality, in particular its role in promoting spermatozoa motility, as well as the role of phototherapy in modulating assisted reproduction (ART). Additionally, we investigated the strength of evidence in support of the positive impact of photobiomodulation on facilitating ART.

A significant amount of data is available for bench-scale fire assessments. However, there is little surrounding large-scale tests and even less so for bench-to-large scale comparisons. Large-scale tests require more material, time and preparation, making them more expensive than bench-scale assessments. However, large-scale testing is an essential component to bench-scale fire testing. The bench-scale tests must be representative of both large-scale and real fire behaviour to provide an insight into how a material or product will behave in the event of a fire during its end use application. The few existing studies reviewed in this study show more guidance and data is needed, especially on a large-scale. Unfortunately, the data that is presented is done so in an inconsistent manner using various means of presentation, statistical analysis, and modelling that doesn’t show clear comparisons between bench and large scale. Currently, no bench-scale method shows good agreement with large-scale fire behaviour. Overall, there is a need for more large-scale testing and data for direct comparisons to be made.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.

Urban and agricultural runoffs can transport contaminants and pesticides into freshwater ecosystems, particularly in the developing tropics. For instance, organophosphate and pyrethroids pesticides like glyphosate, malathion, and permethrin have been found in tropical streams. The uncontrolled application of these pesticides has become a growing concern due to their adverse effects on various non-targeted organisms. Unfortunately, most studies have focused on a few selected model species, ignoring the effects on other nontarget organisms, which may play an important role in tropical lotic ecosystems. In addition, the biological characteristics of aquatic crustaceans, including their morphology, physiology, and behavior, make them susceptible to toxic chemicals. For this reason, this study used the widely distributed freshwater shrimp Xiphocaris elongata as a model organism to determine the acute toxicity of permethrin, malathion, and glyphosate. Our results show that the proportion of mortality of X. elongata in each concentration group became progressively higher as the concentration of exposure increased. We also found that the synthetic pyrethroid permethrin is the most toxic pesticide tested, followed by organophosphate malathion and glyphosate. Experiments with this freshwater shrimp showed a good control performance and reproducibility for the tested pesticides. This study demonstrated that X. elongata is a suitable test organism that can be a representative bioindicator of pesticide toxicity in tropical streams.

Ants of the genus Solenopsis are important invasive pests in the world. Due to their high dispersion capacity, aggressive behavior and because they feed on various sources of vegetable and animal protein, these insects have caused serious damage to public health and agriculture. The control has usually been carried out through the use of organosynthetic insecticides. However, due to the ecological and environmental impacts caused by the use these products, more sustainable alternatives have been sought for their control. Faced with these problems and due to the scarcity of registered products for the control of these insects, we aimed with this study to synthesize and evaluate the anticidal potential of carvacrol derivatives. The lethal and sublethal effects caused by these derivatives were compared with the essential oil of Lippia gracilis (50.7% carvacrol) and with the base molecule — carvacrol. Carvacryl benzoate was the most toxic derivative to Solenopsis sp. with an LD50 of 3.20 g/ mg. This compound was about 2 and 7.6 times, more toxic than carvacrol at the doses needed to kill 50 and 90% of populations, respectively. The workers of Solenopsis sp. showed a rapid reduction in survival when exposed to carvacrol (LT50 = 8.43h) and carvacryl benzoate (LT50 = 8.87h). Insects treated with sublethal doses of the compounds did not show significant effects on self-cleaning, allogrooming and aggregation, with the exception of those treated with L. gracilis essential oil. The oil increased self-cleaning and reduced allogrooming and aggregation. Ants treated with carvacrol and carvacryl benzoate showed greater distance and speed when compared to the control. These compounds decreased meanders and angular velocity. When live workers were exposed to dead individuals at the LD90 of the compounds, carvacryl benzoate was the derivative that most reduced insects survival, due to horizontal transfer. These results show the potential of the carvacrol derivative — carvacryl benzoate — for the alternative management of ants of the genus Solenopsis sp.

Metal toxicity in soils, along with water runoff, are increasing environmental problems that affect agriculture directly and, in turn, human health. In light of finding a suitable and urgent solution, research on plant treatments with specific compounds that can help mitigate these effects has increased, and thus the exogenous application of melatonin (MET) and its role in alleviating the negative effects of metal toxicity in plants, have become more important in the last few years. MET is an important plant-related response molecule involved in growth, development, and reproduction, and in the induction of different stress-related key factors in plants. It has been shown that MET plays a protective role against the toxic effects induced by different metals (Pb, Cd, Cu, Zn, B, Al, V, Ni, La, As, and Cr) by regulating both the enzymatic and non-enzymatic antioxidant plant defense systems. In addition, MET interacts with many other signaling molecules, such as reactive oxygen species (ROS) and nitric oxide (NO), and participates in a wide variety of physiological reactions. Furthermore, MET treatment enhances osmoregulation and photosynthetic efficiency and increases the concentration of other important antioxidants such as phenolic compounds, flavonoids, polyamines (PAs), and carotenoid compounds. Some recent studies have shown that MET appeared to be involved in the regulation of metal transport in plants, and lastly, various studies have confirmed that MET significantly upregulated stress tolerance-related genes. Despite all the knowledge acquired over the years, there is still more to know about how MET is involved in the metal toxicity tolerance of plants.

T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

Introduction: Childhood obesity is becoming an emerging public health issue as it is associated with increased morbidity and premature deaths. Determinants like the child’s household characteristics, maternal weight before the preconception stage, and maternal weight in childhood are studied. There is no study available to understand the association between overweight women of reproductive age and overweight children under five years of age. Studying these determinants to understand the problem can help in framing policies to intervene in the issue. Methods: The data for the study was collected from the National Family Health Survey 5 (NFHS5). It has been sub-grouped into urban and rural categories. The percentage of women with high-risk Waist-Hip-Ratio (WHR) and the percentage of overweight women were independent variables whereas the percentage of overweight under-five children was dependent. Simple linear regression, multiple linear regression, and Pearson correlation coefficient analysis were done for the collected data. Results: Study shows the percentage of overweight women has increased by 4.1%, and the percentage of overweight children has increased by 2% during the NFHS5 (2019-21) compared to NFHS4 (2015-16). Pearson correlation coefficient (R) is 0.5662 and Ꞵ-coefficient for multiple linear regression is 0.1397 for central obesity in women (%) and percentage of overweight children. Conclusion: Central obesity in women is more common than the overweight. Overweight in women as well as in children under five is increasing. Central obesity in women shows a moderate positive relation with overweight in children under five years.

Emerging evidence has indicated the involvement of extra-hypothalamic kisspeptin and GnRHR in reproductive function. In this study, we evaluate if maternal exposure to the pesticide chlorpyrifos (CPF) and/or a high-fat diet (HFD) have an impact on the expression of kisspeptin and GnRHR in reproductive organ of offspring’s rats. 16 Pregnant rats are divided into 4 groups, control group (n=4), CPF group (4 rats exposed daily to 1/mg/kg/day), HFD group (4 rats randomly fed a 5,25 kcal/g HFD), co-exposed group (4 rats exposed to CPF and HDF). At postnatal development PND60, males and female offspring were sacrificed. The reproductive organs (ovary and testis) were removed and histological, immunohistological analysis and in silico quantification (software Tissuefax, HistoQuest) was assessed to investigate the impact of different treatment on kisspeptin and GnRHR expression in reproductive organs. The main outcomes of the study showed a significant decrease in rat offspring’s body weight in CPF group from PND30 andPND60 (p&lt;0.05 and p&lt;0.01, respectively). Histological analysis shows a significant increase in atretic follicle and abnormal testis structure with germ cell desquamation at CPF exposed group. The immunodetection quantification of protein shows a significant decrease in GnRHR and kisspeptin in HFD and CPF exposed group, respectively in testis rat offspring. Perinatal exposure to CPF and HFD exposure affect the reproduction function of rat offspring.