Organ shortage is one of the most pressing issues with regard to human mortality. This issue is further complicated by the fact that HLA matching is required for patients, leading to restricted choices for transplant. If organs or tissues from non- or partially-HLA–matched donors could be edited such they evade cytotoxic T cells as well as natural killer cells, it would ameliorate the organ shortage problem.

The aim of the study was the comparison of conventional sintering versus additive manufacturing techniques for β-TCP bioceramics, focusing on mechanical properties and biocompatibility. A "critical" bone defect requires surgical intervention beyond simple stabilization. Autologous bone grafting is the gold standard treatment for such defects but it has its limitations. Alloplastic bone grafting using synthetic materials is becoming increasingly popular. The use of bone graft substitutes has increased significantly and current research was focused on optimizing these substitutes, whereas this study compares two existing manufacturing techniques and the thereby produced β-TCP implants. The 3D-printed β-TCP hybrid structure implant was fabricated using two components, a column structure and a freeze-foam, which were sintered together. The conventionally manufactured ceramics were made by pouring. Both scaffolds were characterized according to porosity, mechanical properties and biocompatibility. The hybrid structure had a total porosity of 74.4 ± 0.5%. Microporous β-TCP implants had a porosity of 43.5 ± 2.4%, while macroporous β-TCP implants had a porosity of 61.81%. Mechanical testing revealed that the hybrid structure had a compressive strength of 10.4 ± 6 MPa, significantly lower than the microporous β-TCP implant’s with 32.9 ± 8.7 MPa. Biocompatibility evaluations showed a steady increase in cell proliferation over time for all β-TCP implants, with minimal cytotoxicity. This study provides valuable insight into the potential of additive manufacturing for β-TCP bioceramics in the treatment of bone defects.

Inflammation plays a key role in the development and progression of type-2 diabetes (T2D), a disease characterised by peripheral insulin resistance and systemic glucolipotoxicity. Visceral adipose tissue (AT) is the main source of inflammation early in disease course. Macrophages are innate immune cells that populate all peripheral tissues, including AT. Dysregulated AT macrophage (ATM) responses to microenvironmental changes are at the root of aberrant inflammation and development of insulin resistance, locally and systemically. The inflammatory activation of macrophages is regulated at multiple levels: cell surface receptor stimulation, intracellular signalling, transcriptionally and metabolically. This review will cover the main mechanisms involved in AT inflammation and insulin resistance in T2D. First, we will describe the physiological and pathological changes in AT that lead to inflammation and insu- lin resistance. We will next focus on the transcriptional and metabolic mechanisms described that lead to the activation of ATMs. We will discuss more novel metabolic mechanisms that influence macrophage polarisation in other disease or tissues contexts that may be relevant to future work in insulin resistance and T2D.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

Many anti-tumor effects of group-specific component-derived macrophage-activating factors (GcMAFs) have been reported; however, the specific mechanisms remain unclear. Controlling tumor-associated macrophages (TAMs) in the tumor microenvironment is essential for cancer treatment. This study assessed the role of GcMAF in macrophage activation, elucidated the mechanisms by which it exerts its anti-tumor effects, and determined its effects on TAMs in the tumor microenvironment. GcMAF-stimulated RAW264.7 macrophages and EMT6 breast tumor cells were co-cultured in a 0.4-µm pore cell culture insert, and gene and protein expression and cell viability were evaluated. DNA microarray analysis of GcMAF-stimulated RAW264.7 cells was conducted. The induction of M2 RAW264.7 cells by interleukin (IL)-4 and IL-13 was analyzed. GcMAF stimulation increased the tumor necrosis factor-α and inducible nitric oxide synthase mRNA and protein levels in RAW264.7 cells but decreased the viability of co-cultured EMT6 cells. These results were confirmed in the M2 RAW264M2.7 cells, suggesting that GcMAF exerts anti-tumor effects by inducing the differentiation of macrophages into the M1 type and reprogramming M2 macrophages to the M1 type. The anti-tumor activity of GcMAF via M2-to-M1 macrophage reprogramming could aid in developing novel cancer immunotherapies.

Nose mask is a fomite and its usage was mandatory during the COVID-19 outbreak. Its effectiveness has been established; however, as a fomite, it can harbor opportunistic respiratory pathogens such as Streptococcus spp., which could complicate COVID-19 infections. This study profiled Streptococcus species resident on nose masks obtained from consenting participants. Phenotypic assays and 16S rRNA sequencing were used to identify Streptococcus spp. resident on the interior and exterior of 100 nose masks analyzed. Antibiotic resistance (AMR) was determined with disc diffusion and broth microdilution assays. AMR and virulence makers were profiled with primer-specific PCR amplification. 23% of the analyzed samples had Streptococcus isolates. The isolates were highly resistant to the antimicrobials, including conventional, last-resort antibiotics, disinfectants and antiseptics. All the isolates are multidrug resistant with 80-100% levels of AMR to the 16 antibiotics tested with a Multiple-Antibiotic Resistance index greater than 0.2, indicative of potential pathogens. The isolates harbored tetB, ermB, pbp2B, pbp2b1 (resistance) and lytA, lytA1, ply1, cbpA, lytA, pavA (virulence) markers, which might constitute a serious public health risk. Overall, the study emphasizes the need to assess mask usage and the risks associated with opportunistic pathogens that are resident on frequently used nose masks in the COVID-19 era.

Mesenchymal stem cells (MSCs) hold immense therapeutic potential due to their regenerative and immunomodulatory properties. However, to utilize this potential, it is crucial to optimize their in vitro cultivation conditions. Three-dimensional (3D) culture methods using cell-laden hydrogels aim to mimic the physiological microenvironment in vitro, thus preserving MSC biological functionalities. Cellulosic hydrogels are particularly promising due to their biocompatibility, sustainability, and tunability in terms of chemical, morphological, and mechanical properties. This study investigated the impact of (1) two physical crosslinking scenarios for hydrogels derived from anionic cellulose nanofibers (CNF) used to encapsulate adipose-derived MSCs (adMSCs) and (2) physiological culture conditions on the in vitro proliferation, differentiation, and extracellular vesicle (EV) production of these adMSCs. Our results revealed that additional Ca2+-mediated crosslinking, intended to complement self-assembly and gelation of aqueous to-CNF in the adMSC cultivation medium, adversely affected both the mechanical properties of the hydrogel spheres and the growth of the encapsulated cells. However, cultivation under dynamic and hypoxic conditions significantly improved the proliferation and differentiation of the encapsulated adMSCs. Furthermore, we demonstrated that adMSCs in CNF hydrogel spheres exhibited potential for scalable EV production with potent immunosuppressive capacities in a bioreactor system. These findings underscore the importance of physiological culture conditions and the suitability of cellulosic materials for enhancing the therapeutic potential of MSCs. Overall, our study provides valuable insights for optimizing the in vitro cultivation of MSCs for various applications, including tissue engineering, drug testing, and EV-based therapies.

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs, and able to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials: they exhibit good features in terms of impermeability, deformability and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration: however, this kind of materials lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these mate-rials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields: in the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance and patency will be herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance will be been disclosed.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

Blindness or visual impairment following congenital heart repair is a rare complication. It can be transient or permanent depending in underlying etiology and damage to optic pathway. We report first case of transient blindness following congenital heart repair due to unilateral subdural hematoma in occipital region.

Renal replacement therapy (RRT), widely used in the treatment of renal injury in the course of sepsis, aims to eliminate the toxins and proinflammatory cytokines, involved in the pathomechanism underlying septic shock. Dialysis filters characterised by a high adsorption potential for cytokines in RRT when septic renal injury is the case. It is of key importance in the antibiotics treatment of sepsis to achieve desired values of PK/PD indices. Continuous renal replacement therapy (CRRT) may affect antimicrobial clearance, increasing their elimination in some cases. The aim of this study was to determine the degree of adsorption for linezolid, on three different types of filters used in CRRT. In our in vitro study a continuous veno-venous hemofiltration (CVVH) was conducted using 3 types of filters: polysulfone (PS), polyethyleneimine-treated polyacrylonitrile (PAN PEI) and non-PEI-treated polyacrylonitrile (PAN) filters. Each type of filter was used in 3 CVVH cycles, involving the use of 600 mg of linezolid dissolved in 700 ml of bovine blood or in 700 ml of 0.9% NaCl. In each case the total volume of the obtained solution was 1000 ml. Blood samples, at particular time points, were collected in order to measure drug concentration. The differences in mean drug/NaCl adsorption and drug/ blood adsorption were determined using one-way ANOVA with multiple comparisons by Tukey post-hoc test. A p-value of < 0.05 was considered to be significant. A significant adsorption of linezolid was found for PAN PEI filter, both in samples obtained from bovine blood and 0.9% NaCl solutions, at the endpoint. No significant adsorption was demonstrated on PAN or PS filters. There is a need for in vivo research to confirm the effect of filter type on linezolid concentration in patients undergoing CRRT.

Introduction This study was conducted to validate the findings of a prior study published in JDD in September 2023, which reported that a topical firming and toning body lotion (FTB – SkinMedica®, Allergan Aesthetics, an AbbVie Company, Irvine, CA) upregulated several genes in a UV irradiated 3D full-thickness human skin model, outperforming other products, including TransFORM Body Treatment with TriHex Technology® (ATF – Alastin Skincare®, a Galderma company Fort Worth, Texas, USA ). Given the unique response reported for FTB, we conducted this study to assess the reproducibility of these results and explore gene expression at multiple time points, along with validating protein expression in an ex vivo model. Materials and Methods Experiments were conducted using an ex vivo model with photodamaged skin from facelift patients, under an Institutional Review Board approved study. Skin samples were processed, cultured in transwells with Skin Media, and treated daily with either TransFORM or FTB for 7 days. A control group was left untreated. Gene expression was assessed using RT-PCR on days 1 and 3, immunofluorescence after 3 and 7 days of treatment. Skin samples were fixed, paraffin-embedded, sectioned, and stained with an anti-tropoelastin antibody. Fluorescence detection and imaging were conducted to assess protein expression changes. Results Gene expression data from our study and the initial study showed a few similarities but multiple discrepancies. In particular, as opposed to results previously reported at only the 24-hour time point, additional time points showed complete reversal of many of these results. For example, COL1A1 expression at 24 hours was similar for FTB in both studies but differed for TransFORM which showed higher levels at 24 hours. However, at day 3, COL1A1 expression decreased markedly for FTB and was sustained for TransFORM. Other genes, such as COL3A1, COL5, ELN, VEGFC, ATG7, ATG12, BECN1, POMP, PSMB5, and PSMB6, exhibited varying expression patterns between the studies and across different time points. From a translational perspective, histological analysis showed that TransFORM enhanced elastin fiber presence in the dermal-epidermal junction (DEJ) more effectively than FTB at both day 3 and day 7. FTB-treated samples maintained a gap in the DEJ, while TransFORM-treated samples exhibited increased cellular proliferation and DEJ undulation, indicative of a healthier regenerative response. Conclusion This study highlights the problems of examining data and drawing conclusions using a single point of examination. In addition, when a study reports positive results for only 1 product among a range of 8 competitive products, further questioning is essential to exclude the possibility of the experimental model favoring that particular product. The additional 3-day timepoint and further translational examination of histological changes, paints a completely different picture to that reported in the prior publication TransFORM outperformed FTB in most gene expression and histological parameters when assessed over multiple time points in a physiologically relevant ex vivo model.

Although researchers have proposed various indentation size effect (ISE) models, these models often involve different form and number of parameters that can make our wonder which is the best in existed ISE models. Three types of ISE test data, namely, normal ISE, reverse ISE and transition of normal to reverse ISE, are used to evaluate the sixteen ISE models. The comparatively study indicates that H-J, N-G-Fs, N-G-H, N-G-A and N-G-Qs models can accurately predict the normal ISE. The reason for this is that the friction stress that is not related to dislocation activities or the indentation size effect of plastic zone has been introduced into these models. Therefore, these two factors should be considered in future ISE models. The sixteen ISE models are originally proposed to describe the normal ISE of different materials. However, to our surprise, some of these models are able to capture the reverse ISE and the transition of normal to reverse ISE of different materials. The determination coefficients (DC) of the sixteen ISE models are also determined for different materials. For reverse ISE, the highest DC value for NiCSi, TC4 and PED Ni are given by the EXP, N-G-Fs and N-G-A models, respectively. For the transition of normal to reverse ISE, the N-G-YC, N-G-Fs, and N-G-H models produce the maximum DC for ZrO2, Cu and Y2O3-ZrO2, respectively. Moreover, the mean DC of the N-G-Fs model is the maximum among the sixteen ISE models, followed by the N-G-H model, but they cannot accurately predict the reverse ISE. Therefore, the N-G-Fs and N-G-H models should be further modified to accurately predict the reverse ISE.

: Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth and progression of ovarian tumor cells. However, no attention has been shown to their origin so far. It has been mainly assumed that CAFs in primary OC arise from the activation of resident fibroblasts. Here, we compare CAFs with ovarian location to CAFs found in peritoneal implants from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial-related markers. Therefore, as in peritoneal carcinomatosis, CAFs in primary ovarian carcinomas could be originated via a mesothelia-to-mesenchymal transition (MMT) process. The detection of mesothelial-derived CAFs in tumors confined to the ovary and associated biomarkers could be the key to early detection of peritoneal spread in affected patients.

Macrophages are well known for the involvement in the biocompatibility, as well as biodistribution, of nano(bio)materials. Although there are a number of rodent cell lines, they may not fully recapitulate primary cell responses; particularly for those of human cells. Isolation of tissue resident macrophages, from humans, is difficult and may result in insufficient cells with which to determine the possible interaction with nano(bio)materials. Isolation of primary human monocytes, and differentiation to monocyte-derived macrophages, may provide a useful tool with which to study, further, these interactions. To that end, we developed a standard operating procedure for this differentiation, as part of the REFINE project, and used it to measure the secretion of bioactive molecules from M1 and M2 differentiated monocytes in response to model nano(bio)materials, following an initial assessment of pyrogenic contamination which may confound, potential, observations. The SOP was deployed in two partner institutions with, broadly, similar results. The work presented here shows the utility of this assay but, highlights the relevance of donor variability in responses to nano(bio)materials. Whilst donor variability can provide some, logistical, challenges to application of such assays, this variability is much closer to the heterogeneous cells that are present in vivo, compared to homogeneous, non-human, cell lines.

PARP inhibitors are used in tumor therapy exploiting their inhibitory role in DNA repair. Radiation therapy leads to DNA damage in the affected region comprising both tumor tissue and adjacent normal tissue. In addition, radiotherapy has long-standing effects on DNA integrity. The mechanisms for this are not well understood. We studied normal tissue damage of the lung after application of ionizing radiation (IR) in two well established rat models comprising both external (eIR) and internal (iIR) ionizing radiation. We found a nearly complete (~350-fold) loss of PARP-1 in the irradiated tissue in both models but no change in PARylated protein. This may be explained by the strong decrease in both ARH3 and PARG, both deparylating enzymes. We demonstrate, that of all these proteins are expressed in type II pneumocytes, but also in type I pneumocytes and the bronchiolar epithelium. The data suggest a severe disturbance of PARylation in these cells which may affect their major functions such as maintenance of the integrity of the alveolar wall. It is likely that the application of PARP inhibitors could have cumulative effects in radiation-damaged normal tissue.

Macrophages are essential innate immune cells characterized by a high diversity and plasticity. In vitro, their full dynamic range of activation profiles include the classical pro-inflammatory (M1) and the alternative anti-inflammatory (M2) program. Bistability usually arises in biological systems that contain a positive-feedback loop or a mutually inhibitory, double-negative-feedback loop, which are common regulatory motifs reported for macrophage transitions from one activation state to the other one. This switch-like behavior of macrophage is observed at four different levels. First, a decision-making module in signal transduction includes mutual inhibitory interactions between M1 (STAT1 and NF-KB/p50-p65) and M2 (STAT3 and NF-KB/p50-p50) signaling pathways. Second, a switch-like behavior at the gene expression level includes complex network motifs of transcription factors and miRNAs. Third, those changes impact metabolic gene expression leading to several switches in energy production, NADPH and ROS production, TCA cycle functionality, biosynthesis and nitrogen metabolism. Fourth, metabolic changes are monitored by specialized metabolic sensors coupled to AMPK and mTOR activity to provide stability by maintaining the signals to promote either M1 or M2 activation. The targeting of robust molecular switches has the potential to treat a broad range of widespread diseases such as sepsis, cancer or chronic inflammatory diseases.

Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections.

Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia inducible factors, HIF-1a and HIF-2a, and subsequent expression of the HIF-a target VEGF-A during Leishmania major infection. However, the factors responsible for HIF-a activation are not known. We hypothesize hypoxia and pro-inflammatory stimuli contribute to HIF-a activation during infection. RNASeq on leishmanial lesions found transcripts associated with HIF-1a signaling are induced. To determine whether hypoxia contributes to HIF-a activation, we followed the fate of myeloid cells infiltrating from the blood and into hypoxic lesions. Recruited myeloid cells experience hypoxia when they enter inflamed lesions, and the length of time in lesions increases their hypoxic signature. To determine whether pro-inflammatory stimuli in the inflamed tissue can also influence HIF-a activation, we subjected macrophages to various pro-inflammatory stimuli and measured VEGF-A. While parasites alone did not induce VEGF-A, and pro-inflammatory stimuli only modestly induce VEGF-A, HIF- stabilization increases VEGF-A during infection. HIF-a stabilization does not impact parasite entry, growth or killing. Alternatively, the absence of ARNT/HIF- signaling enhances parasite internalization. Altogether, these findings suggest HIF-a is active during infection, and while macrophage HIF-a activation promotes lymphatic remodeling through VEGF-A production, HIF-a activation does not impact parasite internalization or control.

Methylmercury (MeHg) intoxication is a global health concern. Although MeHg neurotoxicity is well-recognized, less is known about MeHg's effects on metabolism. In this study, we evaluated MeHg intoxication (20mg/L in drinking water for 20 days) effects on liver and epididymal white fat (EWF) in young ApoE knockout (ko) and wild-type mice. The former is well-known to show spontaneous dyslipidemia. Hg levels in hair, liver, and EWF were measured to assess the degree of MeHg exposure. We also evaluated body weight gain, plasma triglycerides, total cholesterol levels, and liver injury by assessing steatosis score, AST, ALT, SOD, and TBAR levels. To evaluate EWF, we analyzed mean wet weight and adipocyte diameter, plasma leptin levels and metabolomics. Hg levels were markedly higher among intoxicated mice. ApoE ko mice showed higher Hg in the hair but lower levels in the liver and EWF than wild-type controls. Among wild-type mice, MeHg compromised weight gain and increased liver TBAR levels compared to non-challenged controls. Among non-intoxicated mice, ApoE deficiency significantly increased triglyceride, total cholesterol, and liver transaminases with reduced EWF wet weight, hepatic SOD, and plasma leptin levels. MeHg accumulation together with ApoE deficiency elevated total cholesterol, triglycerides, hepatic transaminases, and TBARS. We found distinct EWF metabolite activity in different scenarios of ApoE deficiency and MeHg intoxication, highlighting increased cardiovascular risk especially when both challenges occur. Further studies are required to elucidate the underlying mechanisms involved in these effects and the target nutritional interventions in most need to ameliorate them.

Despite increased hurricane intensity, the U.S. Gulf of Mexico coast has experienced dramatic coastal population increase of 24.5% from 2000 to 2016. However, in coastal Louisiana areas with dramatic wetland loss, parishes have experienced population declines and lower rates of population growth. Therefore, understanding the magnitude of the effect of wetland loss as a main driver in population loss in coastal Louisiana is critical. Using regression analysis, this study finds that wetland loss has a significant and persistent negative effect on population growth in coastal Louisiana. This effect resulted in a reduction in the population growth rate in coastal parishes over time. A counterfactual simulation was conducted to estimate the potential population size in the absence of wetland loss from 1990 to 2021. On average, the effect of 1 hectare of wetland lost causes a reduction of approximately 1000 persons. This indicates that for the year 2021, the population was approximately 18% lower than the population that would have existed in the absence of wetland loss. This research underscores the role of wetlands in providing direct and indirect benefits to people in coastal Louisiana that are ultimately reflected in its population levels.

Commonly macrophages are categorized into M1 and M2 subsets. M1 macrophages are defined as inflammatory cells and may contribute to tissue injury, while, M2 macrophages play a central role in tissue remodeling and control of immune responses. It seems that the existence of these cells in graft location is effective for control of inflammation and improvement of transplantation consequences. Although the relative contribution of M2 cells in organ transplantation is not clear, the accumulation of these cells in acute and chronic injury models of transplantation was shown. In some cases, the depletion of M2 cells leads to the amelioration of disease; however in other causes, skewing the response in M2 cells leads to an augmentation of graft fibrosis and worsening of graft condition. In spite of these findings, the benefits of such strategies and their implications in human disease are not clearly understood. The purpose of this mini-review is to highlight the role of alternatively activated M2-type macrophages in the improvement or reduction of the kidney transplantation outcome.

Tissue-like phantoms are widely used as a model for mimicking the optical properties of live tissue. This paper presents the results of a diffusion reflection method as well as fluorescence lifetime imaging microscopy measurements of fluorescein-conjugated gold nanorods in solution as well as inserted in solid tissue-imitating phantoms. A lack of consistency between the fluorescence lifetime results of the solutions and the phantoms raises a question about the ability of tissue-like phantoms to maintain the optical properties of inserted contrast agents.

Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customized biomaterials able to mimic ECM functionalities represent one of the major strategy to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review new strategies and future perspectives of such synthetic cell microenvironment will be highlighted.

Aortic stenosis (AS) is a prevalent valvular disorder that often requires surgical aortic valve replacement (SAVR) to alleviate symptoms and improve survival. However, the selection of an appropriate prosthetic valve size is crucial to avoid patient-prosthesis mismatch (PPM), which can lead to suboptimal hemodynamic outcomes. Von Willebrand factor (VWF), a key component of hemostasis, has been shown to be altered in AS patients and may contribute to the hemostatic imbalance observed following valve replacement. This prospective study aimed to investigate the impact of PPM on postprocedural VWF levels in patients undergoing SAVR for severe AS. The study included 31 consecutive patients diagnosed with severe AS who underwent SAVR. By focusing on the relationship between PPM and VWF dynamics, this study sought to provide valuable insights into the potential role of VWF as a marker for hemostatic changes associated with PPM, ultimately informing strategies for optimal valve selection and perioperative management to minimize complications.

Background and Objectives: Wilson disease (WD) is a disorder of copper metabolism caused by genetic muta-tions in the ATP7B gene which lead to the accumulation of copper in the body. The aim of the present study is to investigate the severity of WD in patients in Romania. Materials and Methods: This study was conducted us-ing an online questionnaire consisting of 32 questions in a group of patients suffering from Wilson disease. Results: The study included 67 people aged 7 to 56 with WD. The most common symptoms of the participants were hepatic and neurological in 22 cases (32.8%). The most common neurological symptom in the assessed cases was muscle stiffness (49.5%), followed by tremor (45%), and speech disorders (40.5%). The Kay-ser-Fleischer ring was present in 50.7% of the participants. The most commonly used drug treatment in the participants was D-penicillamine (77.61%). Conclusions: The severity of WD is based on many aspects, the most important being early diagnosis and access to treatment throughout the year. The prognosis is favorable with early diagnosis and treatment, but it is crucial to diagnose individuals before they develop major symp-toms. Therefore, advances in WD screening can lead to an earlier diagnosis and better results.

The breast holds significant importance in women's lactation process. The breast has diverse tissues such as glandular, Cooper’s ligament, lactiferous ducts, adipose, muscles, and skin with various mechanical properties. Most soft tissues exhibit nonlinear, viscoelastic, and anisotropic mechanical behaviour. Stiffness is one of the commonly used mechanical properties for measuring mechanical behaviour in soft tissues. However, this is typically used in simplifying cases where analysis is limited to within the linear elastic region. Young’s modulus is the prevailing measure for quantifying stiffness in tissues. This systematic review examines commonly used techniques for mechanically characterising breast soft tissues to close the gap in the literature. Additionally, this systematic review summarises the mechanical behaviour of the breast tissues available in the literature and highlights the uncovered areas to understand the mechanical behaviour of breast tissues fully. These include a) more mechanical behaviour studies, allowing more accurate modelling for other applications, b) Viscoelastic analysis studies, and c) mechanical analysis on other breast tissues, such as the lactiferous duct, also known as the milk duct. The data obtained in the review can be used as inputs in computational models to analyse the behaviour of the breast tissues.

Leishmaniasis is a complex infectious parasitic disease caused by protozoa of the genus Leishmania, belonging to a group of neglected tropical diseases. It poses significant global health challenges, particularly in socio-economically disadvantaged regions. Macrophages, as innate immune cells, play a crucial role in initiating the inflammatory response against the pathogens responsible for this disease. Macrophage polarization, the process of differentiating macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, is essential for the immune response in leishmaniasis. The M1 phenotype is associated with resistance to Leishmania infection, while the M2 phenotype is predominant in susceptible environments. Notably, various immune cells, including T cells, play a significant role in modulating macrophage polarization by releasing cytokines that influence macrophage maturation and function. Furthermore, other immune cells can also impact macrophage polarization in a T-cell-dependent manner. Therefore, this review comprehensively examines macrophage polarization's role in leishmaniasis and other immune cells' potential involvement in this intricate process.

Liquorpheresis (CSF filtration) comprises a therapeutical approach that has been proposed to treat several neurological conditions where antibodies, inflammatory mediators or abnormal peptides are the cause or play an important role in the pathogenesis of the disease. CSF replacement may be an alternative approach not explored so far. Here, we review previous experiences in the use of liquorpheresis in autoimmune and degenerative neurological diseases. Then we describe previous developments and provide some new technical innovations in order to design bidirectional CSF shunting systems. These systems can be complemented either with a deposit of artificial CSF or with a CSF filter, allowing CSF replacement or liquorpheresis respectively. Both options would lead to mechanical dilution of the patient’s CSF.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

This paper aimed to evaluate the growth, gas exchange and Chl a fluorescence in ipê-rosa seedlings, subjected to levels of 100, 75, 50 and 25% of water replacement (LWR), in a greenhouse. The morphometric variables of plant height, diameter at stem height, number of leaves and leaflets, root length and volume, plant dry mass and leaf area were evaluated. The potential evapotranspiration of seedlings (ETc) was obtained using direct weighing, considering as a reference the water replacement of 100% of the mass variation between subsequent days; the cultivation coefficients (kc) were obtained by the ratio between ETc and the reference evapotranspiration (ETo) obtained by the Penman-Montheit FAO-56 method. Biomass and evapotranspiration data were combined to determine water sensitivity. Diurnal fluxes of gas exchange (net photosynthesis rate, transpiration rate, stomatal conductance, internal and atmospheric carbon ratio, water use efficiency and leaf temperature) and Chl a fluorescence (Fv/Fm, ΦPSII, ETR, Fv’/Fm’, NPQ and qL) were evaluated. Water restriction caused reductions of 90.9 and 84.7% in the increase in height and diameter of seedlings subjected to 25% water replacement when compared to seedlings with 100% water replacement, while biomass accumulation reduced by 96.9%. The kc values increased throughout the seedling production cycle, ranging from 0.59 to 2.86. Maximum water sensitivity occurred at 50% water replacement, with Ky = 1.62. Maximum carbon assimilation rates occurred in the morning, ranging from 6.11 to 12.50 µmol m-2 s-1. Ipê-rosa seedlings regulate the physiology of growth, gas exchange, and Chl a fluorescence depending on the amount of water available, and only 25% of the water re-placement in the substrate allows the seedlings to survive.

Spider silks, renowned for their exceptional mechanical and biocompatible properties, offer significant potential as scaffolds in tissue engineering. This paper explores the feasibility of using spidroins, the primary proteins in spider silk, to develop scaffolds that closely mimic the extracellular matrix (ECM) essential for tissue regeneration. Spidroins (spider silk proteins) are particularly valuable due to their unique strength, elasticity, and biocompatibility, which support cellular growth and differentiation. The paper examines current methods for producing recombinant spider silk, including using unicellular hosts like E. coli and multicellular systems like transgenic plants and silkworms. It also examines current scaffolds that utilize spidroins and their shortcomings, such as immunogenicity and protein production, which must be urgently addressed for more practical and effective widespread biomedical applications. In addition, it stresses the need for further research to solve these challenges and fully realize the potential of spider silk in biomedical applications.

Alzheimer’s disease (AD) and the therapies of AD with anti-amyloid1-42 (Aβ) monoclonal antibodies are associated with the vascular complications of brain edema, hemorrhage, and cerebral amyloid angiopathy (CAA) termed amyloid-related imaging abnormalities (ARIAs). The neuropathology of normal and AD brains demonstrates that monocyte/macrophages (MMs) are critical in successful brain clearance in healthy brain by up-loading, transporting, and degrading Aβ but fail degradation and clearance in AD patients by releasing Aβ into vessels at the blood-brain barrier, causing vasculitis and ARIAs. The naturally-formed epoxides (EpFAs) of polyunsaturated fatty acids (PUFA’s), including arachidonic, docosahexaenoic, and eicosapentaenoic fatty acids, may repair degradation of Aβ by regulating Aβ-degrading enzymes, inflammatory cytokines, and unfolded protein response (UPR) to endoplasmic reticulum stress in a homeostatic fashion. EpFAs are, however, degraded by the soluble epoxide hydrolase enzyme (sEH) but are protected by the sEH inhibitor (sEHI) TPPU. In the cultures of AD patients’ macrophages, TPPU with the epoxide EEQ, and the cGAS/STING inhibitor H-151 increased uptake of Aβ at 2 hours and degradation of Aβ at 24 hours. In conclusion, the soluble epoxide hydrolase inhibitor TPPU with omega-3 fatty acids and the cGAS/STING inhibitor H-151 increase Aβ uptake and degradation in macrophages of AD patients, and potentially enhancing Aβ clearance in the AD brain.

The color of carcass fat is an important factor in meat quality. To investigate the characteristics and changes in lipid metabolism of SAT in Mongolian cattle at 34 M of age compared with the control group, we evaluated the color, relative expression of genes associated with browning, and profiles of lipid metabolites by using qPCR and non-targeted lipidomics techniques. Overall, the yellowness value and relative expression of mitochondrial biogenesis–specific markers, thermogenic, UCP2, and beige adipocyte marker genes in the SAT of 34 M cattle were higher than those control (p &lt; 0.05). Using multivariate analysis, 172 significantly different lipids (SDLs) were identified. Triacylglycerols (TGs) and phosphatidylcholines (PCs) had high relative contents with abundant unsaturated fatty acids. The upregulation of TGs observed in the SAT of 34 M cattle mainly consisted of medium- and long-chain fatty acids. Pathway analysis demonstrated that 172 SDLs were primarily involved in glycerophospholipid, glycerolipid, ether lipid, and sphingolipid metabolism. In summary, yellow fat of naturally grazed cattle was impacted by many factors such as lipid metabolism, browning genes expression and age. These findings provide new insight into the characteristics and metabolic pathways of adipose tissue in natural grazing Mongolian cattle.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

The potentially active A subunit of coagulation factor XIII (FXIII-A) is an intracellular transglutaminase expressed in various cell types including platelets and monocytes/macrophages. It is involved in stabilizing protein structures by cross-linking through Nε-(?-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque and are important in determining its structural/functional features. Two of their important functions are the accumulation of oxidized LDL in the lipid core, and by cross-linking structural proteins they may stabilize the plaque and protect the thrombi of atherogenic origin against fibrinolytic degradation. It is important to know whether these functions operate in parallel utilizing the same cellular compartments. First, we showed that monocyte-derived human macrophages significantly increase their FXIII-A content when up-taking oxidized LDL. This phenomenon is very likely independent of the process of transformation into foam cells, as the transformation of vascular smooth muscle cells into foam cells fails to result in the expression of FXIII-A. FXIII containing macrophage-like cells are abundant in the plaque and FXIII-A is also present in the extracellular core. Several cells co-stained for FXIII-A and for Oil Red O suggest that expression of FXIII-A and lipid up-take are common features of macrophages present in the atherosclerotic plaque.

This study aimed to identify miRNA editing sites during adipose tissue development in Ningxiang pigs and analyze their characteristics and functions. Based on the small RNA-seq data from subcutaneous adipose tissue samples of Ningxiang pigs at four stages (30, 90, 150 and 210 days), we constructed a developmental atlas of the miRNA editome in adipose tissue of Ningxiang pigs. The characteristics and functions of this editome were further explored through bioinformatics analysis. The findings revealed that a total of 505 miRNA editing sites were identified with C-to-U editing types being the most prevalent, followed by U-to-C, A-to-G and G-to-U. Importantly, these four types of miRNA editing exhibited a base preference. The number of editing sites showed obvious differences among age groups, with the highest occurrence of miRNA editing events observed at 90 days of age and the lowest at 150 days of age. In the miRNA seed region, a total of 9 miRNA editing sites were identified with significant differences in editing levels (P &lt; 0.05), and located in ssc-miR-23a, ssc-miR-27a, ssc-miR-30b-5p, ssc-miR-15a, ssc-miR-497, ssc-miR-15b, and ssc-miR-425-5p, respectively. Target gene prediction and enrichment analysis revealed that the editing of miR-497 may potentially regulate fat deposition by inhibiting adipose synthesis via influencing target binding. These results provide new insights into the regulatory mechanism of pig fat deposition.

Tumor-associated macrophages are a key component in the tumor microenvironment, secreting extracellular vesicles (EVs) such as exosomes and other various factors for intercellular communication. However, macrophage-derived EVs heterogeneity and their cytotoxicity to cancer cells has not been well understood. Here, we aimed to separately isolate various types of macro-phage-EVs by size exclusion chromatography (SEC) method and investigate EV transmission and cytotoxicity to oral cancer cells. For fluorescence-labeling of cellular and EV membranes, palmitoylation signal-fused GFP and tdTomato were expressed in THP-1 monocytic cells and HSC-3 oral cancer cells, respectively. We found that fluorescence-labeled EVs secreted by macrophages were highly transmissive to oral cancer cells than those from parental monocytic cells. In a co-culture system and conditioned medium (CM), a macrophage-secreted unidentified factor was cytotoxic to oral cancer cells. We fractionated macrophage-derived EVs by the SEC method and performed western blotting to characterize various EV types. Three fractions were characterized: small exosomes (EXO-S: < 50 nm) fraction containing HSP90α, HSP90β, CD63 (EV marker) and β-actin; large exosomes (EXO-L: 50-200 nm) fraction containing CD9 (EV marker) and HSP90β; large EVs (100-500 nm) fraction. Notably, the macrophage-derived small exosomes fraction was cytotoxic to oral cancer cells, while large exosomes and large EVs were not. There-fore, it was implicated that macrophage-derived small exosomes are cytotoxic with high trans-mission potential to cancer cells.

Geopolymers, made from aluminosilicate raw materials, offer significant environmental advantages over conventional concrete (CC) mixes. This study explores the compressive strength, setting time, and durability of geopolymer concrete (GPC) cylinders, some of which include an additional ordinary portland cement (OPC) mix. Consistent material composition and testing methods are emphasized to achieve reliable results. MATLAB was utilized to develop and assess a neural network model predicting the compressive strength of GPC based on key variables. The model was validated using 16 experimental samples and 1047 samples from various studies. The performance plot displayed the Mean Squared Error (MSE) over iterations, identifying the best training performance at epoch 658 with an MSE of 5.3408. The Error Histogram highlighted distribution errors between predicted and actual compressive strength values, with the highest range from -1.015 to 0.3587, meaning that the predicted values were mostly within a small margin of error from the actual values. This narrow error range indicates that the ANN model has high accuracy in its predictions, as most errors are small and clustered around zero, demonstrating reliable performance in estimating compressive strength. Regression analysis showed varying correlation coefficients (training set R=0.98373, test set R=0.88164, and whole set R=0.96982), indicating adequate predictive accuracy. The results demonstrate that properly trained neural networks can effectively predict the compressive strength of GPC, highlighting its potential as a sustainable construction material.

Progress in macrophage research is crucial for numerous applications in medicine, including cancer and infectious diseases. However, the existing methods to manipulate living macrophages are labor intense and inconvenient. Here we show that macrophage membranes can be reconstituted after storage for months at 4C, with their CD206 receptor selectivity and specificity being similar to that in the living cells. Then, we have developed a mannose ligand, specific to CD206, linked with PEG as IR spectroscopy marker to detect binding with the macrophage receptor. PEG was selected due to its unique adsorption band of C-O-C group at IR spectra, which does not overlap with other biomolecule’s spectroscopic feature. Next, competitive binding assay versus the PEG-bound ligand, has enabled selection of other higher-affinity ligands specific to CD206. Further, those higher-affinity ligands were used to differentiate activated macrophages in patient’s bronchoalveolar (BAL) or nasopharyngeal (NPL) lavage. CD206- control cells (HEK293T) showed only non-specific binding. Therefore, biochips based on reconstituted macrophage membranes as well as PEG-trimannoside as an IR spectroscopic marker, can be used to develop new methods facilitating macrophage research and macrophage-focused drug discovery.

Corneal diseases are the third leading cause of blindness worldwide. There are numerous causes of corneal blindness, and the common treatment for this condition often involves corneal tissue transplantation, such as Descemet's Membrane Endothelial Keratoplasty (DMEK). DMEK has been established as the preferred surgical technique for the treatment of corneal endothelial disorders. The success of DMEK depends largely on the quality of the donor endothelial cells and the trans-plantation procedure. However, the scarcity of suitable donor tissue and the sensitivity of endo-thelial cells pose a major challenge. In recent years, tissue engineering has attracted attention as potential solutions to these problems. This review offers an outline of the current landscape of DMEK in the context of bioengineering, exploring various methodologies, advancements, and fu-ture prospects.

This study presents an innovative method for producing thermosensitive bio-ink from chitosan hydrogels saturated with carbon dioxide and agarose. It focuses on a detailed characterization of their physicochemical properties and potential applications in biomedicine and tissue engineering. The ORO test approved rapid regeneration of the three-dimensional structure of chitosan-agarose composites in the unidirectional bench press simulation test. The diffusion of dyes through chitosan-agarose hydrogel membranes strongly depended on the share of both polymers in the composite and the molecular weight of the dyes. Glucose, as a nutrient marker, also diffused through all membranes regardless of composition. Biocompatibility assessment using MTT tests on 46BR.1N fibroblasts and HaCaT keratinocytes confirmed the safety of the bioink. The regenerative potential of the bioink was confirmed by efficient cell migration, especially HaCaT. Long-term viability studies showed that chitosan-agarose scaffolds, unlike the agarose ones, support cell proliferation and survival, especially 14 days after bioink extrusion. Experiments in a skin wound model in mice confirmed the biocompatibility of tested dressing and the beneficial action of chitosan on healing. Studies on vessel formation in chicken embryos highlight the potential of the chitosan-agarose composition for enhancing proangiogenic effects. This composition meets all entry criteria and possesses excellent biological properties.

Solid waste management is a major environmental challenge, especially in developing countries, with increasing amounts of waste glass (WG) and waste plastics (WP) not being recycled. In Ethiopia, managing WG and WP requires innovative recycling techniques. This study examines concrete properties with WG and WP as partial replacements for fine aggregate. Tests were conducted on cement setting time, workability, compressive strength, splitting tensile strength, and flexural strength. Concrete grade C-25, with a compressive strength of 25 MPa, was prepared using an optimum ratio of 14% WG and 6% WP. Mechanical properties were tested at 7 and 28 days of curing. At 20% replacement, workability decreased at water-cement ratios of 0.5 and 0.6 but remained stable at 0.4. Thus, a 0.4 ratio was used. For 10% replacement, compressive strength increased by 12.55% and 6.44% on the 7th and 28th days, respectively. At 20% replacement, compressive strength decreased by 14.35% and 0.73% on the 7th and 28th days, respectively. On the 28th day, splitting tensile strength at optimum replacement was 4.3 MPa, an 8.5% reduction from the control mix. However, flexural strength increased by 19.7%, from 12.46 MPa to 15.52 MPa. Overall, WG and WP improved flexural strength but slightly reduced splitting tensile strength.

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-vivo tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract.

The clinical features of increasing muscle weakening are shared by a diverse set of illnesses known as muscular dystrophies. In early childhood, males with Duchenne muscular dystrophy (DMD) exhibit proximal muscle weakening and calf enlargement, making it the most frequent X-linked disease of muscular dystrophy in children. Development of motor skills is typically delayed, and wheelchair confinement eventually leads to early death from heart or lung problems. In terms of function, ambulation, quality of life, and life expectancy, treatment approaches like corticosteroid therapy and intermittent positive pressure breathing have improved. This is a case report of a 6-year-old kid who had early ambulatory stage Duchenne Muscular Dystrophy and complained to the neuro-physiotherapy department about frequent falls, walking difficulties, and dyspnea when walking. Other grievances included being unable to get off the ground and having trouble ascending stairs. He had physiotherapy and dynamic neuromuscular stabilization for his complaints. The main goals of treatment were educating the family, respiratory training, preventing ankle plantar flexors, maintaining strength, balance and gait training.

Adeno-associated viral (AAV) vectors can be used for gene delivery. AAV.CAP-Mac was recently developed; it can cross the blood-brain barrier and transduce cells throughout the CNS. However, some brain regions were not transduced in adult rhesus monkeys. Additionally, AAV vectors can only package 5 kb of DNA. Also, AAV vectors may be genotoxic and cytotoxic, especially at high doses. Finally, AAV vectors are very expensive to produce at sufficiently high titers for treatment. Off-the-shelf cell-based delivery systems wherein the cells can infiltrate the target tissue and be hyper-motile would be ideal. Also, mRNA-based gene editing would be a transient treatment, and thus be much safer.

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

Poikilodermatous plaque-like hemangioma (PPH) is a recently described clinical and pathological entity, with only 18 cases reported in the literature. Although uncommon, this benign condition presents consistent clinical and histological findings. We present a new case of PPH in an 81-year-old male and review the existing literature. The persistence over time and the need to distinguish PPH from more significant lesions underscore the importance of its clinical and pathological recognition.

Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.

This study presents an innovative approach for the utilization of industrial by-products and municipal waste in the production of sustainable and environmentally friendly cement mortar. We explored stabilized stainless-steel reduced slag (SSRS) and polyethylene (PE) plastic waste as partial replacements for aggregates. Various engineering properties of the resulting cement mortar specimens, including slump, slump flow, compressive strength, flexural strength, tensile strength, water absorption, and ultrasonic pulse velocity (UPV), were investigated through comprehensive experimental tests. The influence of different water-cement (w/c) ratios and substitution amounts on the engineering properties of the cement mortar samples was thoroughly examined. The findings revealed that an increase in PE substitution adversely affected the overall workability of the cement mortar mixtures, whereas an increase in SSRS amount contributed to enhanced workability. As for the hardened properties, a consistent trend was observed for both cases, with higher w/c ratios and substitution amounts leading to reduced mechanical properties. Water absorption and UPV test results validated the increased formation of porosity with higher w/c ratios and substitution amounts. This study proposes a promising method to effectively repurpose industrial by-products and municipal wastes, transforming them into sustainable construction and building materials. Additionally, a comparative analysis of transportation costs and carbon footprint emissions between SSRS-cement mortar and PE-cement mortar was conducted to assess their environmental impact and sustainability. Generally, higher w/c ratios and replacement levels corresponded to reduced carbon footprint. The geographical location of the source of SSRS and PE remains a challenge and studies to overcome this challenge must be further explored.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGene database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined using Mendelian randomization. A total of 169 genes that exerted trans-regulatory impacts on 692 genes were identified. 90% of the genes (N=749) aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. The identified network displayed the scale-free topology. This provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and ALDH2 overexpression contributes to obesity. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The network identified in this study showed scale-free topology indicating the hub genes of a GRN could be targeted to prevent disease outcomes.

This study investigated the effect of partially replacing fish meal with krill and copepod meals in inert diets, co-fed with shrimp, on the growth and nutrient digestibility of long-snout seahorse (Hippocampus guttulatus). A control diet (Diet 1) using raw starch and four experimental diets with similar protein (≈44.8%) and energy (≈15.1 MJ/kg) levels were tested. Diet 2 used fish meal as the sole protein source, while in Diets 3-5, krill and copepod meals replaced 44% of the fish meal. Seahorses fed Shrimp + Diets 2-5 showed significantly higher growth rates (P &lt; 0.05) than those fed Shrimp + Diet 1, though there were no significant growth differences among Diets 2-5. Digestibility of dry matter (46.1% to 72.2%), lipids (73.3% to 85.5%), crude protein (89.8% to 95.8%), energy (82% to 92.2%), and phosphorus (28.7% to 64.4%) varied with diet, being consistently lower in seahorses fed Shrimp + Diet 1. As an agastric species, H. guttulatus did not exhibit impaired digestibility for any of the tested nutrients, minerals, or energy. This study suggests that crustacean meals can effectively substitute fish meal in inert diets for this species, contributing to the sustainability and optimization of captive seahorse husbandry practices.

Tissue engineering, also called “regenerative medicine”, refers to attempt to create functional human tissue from cells in laboratory. This is a field that uses living cells, biocompatible materials, suitable biochemical and physical factors and their combinations, to create tissue-like structures.. To date, no tissue engineered skeletal muscle implants have been developed for clinical use, but it may represent a valid alternative to treat volumetric muscle loss in the near future. Herein, we reviewed the literature and showed different techniques to produce synthetic tissues with the same architectural, structural and functional properties of native tissues.

Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with myeloid-derived suppressor cells (MDSCs) in tumor microenvironments regulates cancer progression. Immunodeficient mice lacking T cells are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The xenograft tumor microenvironment, comprising human cancer and mouse host cells, exhibits more complex bidirectional signaling and function than a syngeneic tumor microenvironment. Here human and mouse colorectal cancer cells were transplanted into nude mice to elucidate differences in macrophage, DC, and MDSC functions in human xenograft and mouse allograft tumor models. Plasma interferon-γ and interleukin-18 concentrations in the former model after intraperitoneal lipopolysaccharide (LPS) administration were significantly higher than those in the latter model and non-transplanted control group. Splenic MHC class I, II, and CD80 expression increased in CD11b+ and MDSC populations after LPS administration in only the xenograft tumor model. The number of CD80- and MRC1-expressing cells decreased upon LPS administration in only the xenograft tumor. These results suggxest that macrophages and DCs function normally in xenograft tumor models, whereas their functions in response to LPS administration vary in allograft tumor models.

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

An event of increasing interest during host-pathogen interactions is the differentiation of patrolling monocytes (MOs) and the polarization of naive MOs into macrophage subsets (MФs). Therapeutic strategies aimed at modulating this event are under investigation. This review focuses on the mechanisms of induction, development, and profile of MФs polarized toward classically proinflammatory (M1) or alternatively anti-inflammatory (M2) phenotypes in response to bac-teria, fungi, parasites, and viruses. It highlights nuclear (PPARγ), cytoplasmic, and cell surface receptors (pattern recognition receptors/PPRs), microenvironmental mediators, and immune signaling. MФs polarize into phenotypes: M1 MФs, activated by IFN-γ, pathogen-associated mo-lecular patterns (PAMPs, e.g. LPS)/DAMPs and membrane-bound PPRs ligands (TLRs/CLRs lig-ands); or M2 MФs (a, b, c and d), induced by IL-4, -10 and -13, antigen-antibody complexes, and helminth PAMPs. The kinetics of M1 and M2 polarization evolve in a pathogen-specific manner, with or without canonicity, and can vary widely. Ultimately, this can result in varying degrees of host protection or more severe disease outcome. While the host is driving an effective MФs po-larization, pathogens are attempting to shift it to increase pathogenicity. The latter results from a bias toward an ineffective M1 or M2 response due to microbial virulence factors, culminating in pathogen evasion of host defenses. Plasticity of M1/M2 phenotypes is also ensured by cellu-lar/genomic reprogramming. Because modulation of this event can occur at multiple points, providing a therapeutic/vaccine design target to boost microbicidal (M1) or tissue repair (M2) response during the inflammation-to-resolution transition; new insights and emerging perspec-tives may have clinical implications.

Macrophages are the key effector cells of innate immunity which show two polarized states: M1, classically activated and M2, alternatively activated. Tumor-associated macrophages (TAMs) which usually show M2 polarization, are immunosuppressive cells that enhance tumor metastasis and invasion. Also, enrichment of TAMs is known to be closely associated with poor prognosis of cancer patients. Therefore, TAMs are considered to be promising targets for immunotherapy. Importantly, tumor-derived exosomes emerged as a crucial player in immune regulation which can remodel the tumor microenvironment towards immunosuppressive state. Of note, few studies have shown that exosomes could induce polarization of macrophages towards M2 type in tumor condition, while others showed activation of M1 or mixed phenotype. Considering the role of TAMs in cancer, there is an urgent need to decipher the exosome-mediated cross-talk between tumor cells and macrophages.For this, we used murine model of Dalton’s lymphoma (DL), wherein, firstly, we evaluated increased exosome burden by assessing exosome level in serum as well as in various tissues of tumor-bearing host. Next, proteomic profiling of lymphoma-derived exosomes was done which revealed the presence of immunomodulatory proteins. Of note, these proteins were known to alter the macrophage polarization. In order to assess the effect of these exosomes on macrophages, we performed in vitro study using RAW264.7 cells. In vitro study revealed that frequent uptake of exosomes mediated a morphological change in macrophages which reduced their phagocytic activity. In parallel, exosomes increased reactive oxygen species (ROS) level and inhibited LPS-induced nitric oxide (NO) level in macrophages. Also, exosomes upregulated the expression of arginase-1 (an M2 marker) in macrophages but decreased the LPS-induced nitric oxide synthase 2 (NOS2) (an M1 marker) expression. Moreover, we observed a pro-tumoral cytokine profile in macrophages incubated with exosomes. Our study suggests that exosome load increases in lymphoma-bearing hosts systemically. Importantly, lymphoma-derived exosomes mediate the activation of macrophages towards pro-tumoral M2 type. Our results give an insight into the exosome-mediated tumor and immune cell cross-talk which could serve as an important prospect for targeting in cancer immunotherapy.

The main goal of this study was to evaluate sugarcane bagasse ash as a partial cement replacement material. Sugarcane bagasse ash is a by-product of fuel blending in the sugar industry. Yet all economic sugar is obtained after extraction from the cane. The disposal of the discharged waste in agriculture causes environmental problems in the sugar industry. The cement industry also creates environmental problems due to carbon dioxide emissions during cement manufacturing. Initially, bagasse ash samples were collected from the rubble of the Arjo Didessa sugar factory. The crude bagasse ash was sieved with a sieve size of 250µm. The strength of grade C-25 concrete was designed using five different concrete mixture proportions ranging from 5 to 20% cement by weight, including a water-cement ratio of 0.45. Impact strength tests were conducted at 7, 14, 21, and 28 days of age for each replacement ratio. For the experimental work, a total of 60 cubic concrete specimens were cast for compressive strength tests, and 15 cylindrical concrete specimens were cast for water absorption tests. Working compressive strength results indicated that bagasse ash could replace up to 5% of ordinary Portland cement concrete.

Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

Total hip arthroplasty is a complex procedure. The achievements of implantology enabled the development of a faithful representation of hip joint physiology as well as the production of materials that can successfully replace damaged natural tissues. A very important issue is the correct selection of the geometry of the endoprosthesis adequate to the load of the joint. Materials used for endoprosthesis are a metal head and a polymer cup (e.g. PE-UHMW). The main interactions in the endoprosthesis are friction and surface pressure, which must be limited, exceeding them causes the destruction of the biomechanical system - plastic deformation of the polymer and the formation of too large and unacceptable radial clearances. Based on the author's developed calculation method of hip joint endoprosthesis contact parameters, the impact on maximum contact pressure and the angle of contact of the joint load was estimated depending on the diameter of the endoprosthesis and radial clearance. The correctness of changing the values of maximum contact pressure from the mentioned parameters was determined. Correspondingly: an increase in joint load causes a linear increase in the maximum contact pressure; increasing the diameter of the endoprosthesis head - their non-linear decrease, and increasing radial clearance - their increase

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p&lt;0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

The present review compared the efficacy of soft tissue substitutes (STS) and autogenous free gingival graft (FGG) or connective tissue graft (CTG) in mucogingival procedures to increase keratinized tissue (KT) width around teeth and implants. Two independent examiners performed the electronic search on Medline and Cochrane Library based on the following PICO’s format: (P) adult patients; (I) soft tissue substitutes and FGG/CTG; (C) STS vs CTG; STS vs FGG; STS vs CTR; (O) KT width gain; (S) Systematic Reviews, Randomized Controlled Trials. Results showed that around teeth, all biomaterials showed superior performance compared to CAF alone for treating gingival recessions. However, when compared to CTG, ADM yields the most similar outcomes to the gold standard (CTG), even though in multiple recessions CTG still continue to be considered the most favorable approach. Use of STSs (acellular matrix or tissue engineered) in combination with an apically positioned flap resulted in a significantly less gain of KTW compared to what achieved with FGG and APF. Around dental implants, free gingival grafts were deemed more effective than soft tissue substitutes in enhancing keratinized mucosa width.

The clinical application of collagen-based biomaterials is expanding rapidly, especially in tissue engineering and cosmetics. While oral supplements and injectable skin boosters are popular for enhancing skin health, clinical evidence supporting their effectiveness remains limited. Injectable products show potential in revitalizing skin, but safety concerns persist due to challenges in sterilization and the risk of biological contamination. Traditional methods of sterilization (heat and irradiation) can denature collagen. This study addresses these issues by introducing a novel technique: double filtration and low-temperature steam sterilization of a collagen gel. In vitro tests document sterility and confirm that the collagen structure remained intact without modification. An in vivo study found no adverse effects in rats or significant lesions at the implantation site over 13 weeks. These results suggest that this novel method to process collagen gels is a safe and effective skin booster. Advanced processing methods are likely to mitigate safety risks associated with injectable collagen products, though further research is needed to validate their biological effectiveness and clinical benefits.

Lymph nodes are secondary lymphoid organs that appear as bean-like nodules usually <1 cm in size, and they are localized throughout the body. Many antigen-presenting cells such as dendritic cells and macrophages reside in lymph nodes, where they mediate host defense responses against pathogens such as viruses and bacteria. In cancers, antigen-presenting cells induce cytotoxic T lymphocytes (CTLs) to react to cancer cell–derived antigens. Macrophages located in the lymph node sinus are of particular interest in relation to anti-cancer immune responses because many studies using both human specimens and animal models have suggested that lymph node macrophages play a key role in activating anti-cancer CTLs. The regulation of lymph node macrophages therefore represents a potentially promising novel approach in anti-cancer therapy.

Radiotherapy remains a cornerstone in cancer treatment, leveraging ionizing radiation to eradicate malignant cells. Its efficacy, however, is frequently challenged by the heterogeneous sensitivity of tumors and surrounding tissues to radiation. Therefore, understanding the molecular mechanisms underlying radiosensitivity is crucial for improving treatment outcomes. Among the myriad of molecular players involved, the tumor suppressor protein p53 stands out as a central regulator with significant implications for radiosensitivity. Known as the “guardian of the genome,” p53 plays a pivotal role in maintaining genomic stability and orchestrating cellular responses such as cell cycle arrest, DNA repair, apoptosis, and senescence in response to various stress signals, including radiation-induced DNA damage. Activation of p53 triggers the transcription of target genes involved in DNA repair pathways, such as p21, MDM2, and GADD45, facilitating the repair of radiation-induced DNA damage or the elimination of irreparably damaged cells. This, in turn, influences the overall radiosensitivity of tissues. Mutations in the TP53 gene, which encodes p53, are among the most frequent genetic alterations in human cancers. Loss or dysfunction of p53 can compromise the cellular response to radiation, leading to increased resistance to therapy and poorer clinical outcomes. Conversely, intact p53 function is associated with enhanced radiosensitivity due to its ability to promote cell cycle arrest and apoptosis in response to radiation-induced DNA damage. In conclusion, elucidating the molecular mechanisms by which p53 influences radiosensitivity is essential for advancing our understanding of radiation response in cancer cells and developing more effective therapeutic approaches in cancer treatment. This review provides a comprehensive overview of the multifaceted role of p53 in modulating cellular responses to radiation, emphasizing its influence on radiosensitivity.

Piscirickettsia salmonis is an intracellular bacterial fish pathogen that causes piscirickettsiosis, a disease with numerous negative impacts in the Chilean salmon farming industry. Although transcriptomic studies of P. salmonis and its host have been performed, dual host-pathogen proteomic approaches during infection are still missing. Considering that gene expression not always corresponds with observed phenotype, and bacteriological culture studies inadequately reflect infection conditions, to improve the existing knowledge for the pathogenicity of P. salmonis we present here a global proteomic profiling of Salmon salar macrophage-like cell cultures infected with P. salmonis LF-89. The proteomic analyses identified several P. salmonis proteins from two temporally different stages of macrophages infection; some of them related to key functions for bacterial survival in other intracellular pathogens. Metabolic differences were observed in early-stage infection bacteria, compared to late-stage infections. Virulence factors related to membrane, LPS and surface component modifications, cell motility, toxins and secretion systems also varied between the infection stages. Pilus proteins, beta-hemolysin and the T6SS were characteristic of the early-infection stage, while fimbria, upregulation of 10 toxins or effector proteins, and the Dot/Icm T4SS were representative of the late-infection stage bacteria. Previously described virulence-related genes in P. salmonis plasmids were identified by proteomic assays during infection in SHK-1 cells, accompanied by an increase of mobile-related elements. By comparing the infected and un-infected proteome of SHK-1 cells, we observed changes in cellular and ROS homeostasis, innate immune response, microtubules and actin cytoskeleton organization and dynamics, alteration in phagosome components, iron transport and metabolism, and amino acids, nucleoside and nucleotide metabolism, together with an overall energy and ATP production alteration. Our global proteomic profiling and the current knowledge of the P. salmonis infection process allowed us to propose a model of the macrophage-P. salmonis interaction.

Osteoarthritis (OA) poses a growing challenge for the aging population, especially in hip and knee joints, contributing significantly to disability and societal costs. Conventional clinical evaluations, typically performed in controlled settings, face difficulties in capturing the dynamic characteristics of rehabilitation and functioning in real-life scenarios. The study assessed the use of automated unsupervised evaluations in the rehabilitation process for patients after hip and knee replacements. We analyzed data from 1144 individuals who used a digital application after surgery, activity data were collected using the Garmin Vivofit 4. Several parameters such as the Peak 6-Minute Consecutive Cadence (P6MC) and Peak 1-Minute Cadence (P1M) were computed and analyzed on a daily basis. The results indicated that cadence measurements, specifically, can effectively differ among individuals with hip and knee conditions as well as the recovery process. Moreover, these metrics demonstrated a high level of responsiveness in monitoring the progress of recovery, surpassing the effectiveness of simply measuring the total number of steps taken. The study highlighted the capacity of technology-driven, patient-centered rehabilitation to improve accuracy, tailor therapy to individual patients, and increased patient involvement. This research also highlighted the significance of automated, unsupervised assessments in enhancing rehabilitation results for OA patients following hip and knee replacement, as tele-rehabilitation becomes increasingly important.

Scaffold guided breast tissue regeneration (SGBTR) can both transform reconstructive and cosmetic breast surgery. Implant-based surgery is the most common method. However, there are inherent limitations as there is replacement of tissue rather than regeneration. Regenerating autologous soft tissue has the potential to provide a more like-for-like reconstruction with minimal morbidity. Our SGBTR approach regenerates soft tissue by implanting additively manufactured bioresorbable scaffolds filled with autologous fat graft. A pre-clinical large animal study was conducted implanting 100 ml breast scaffolds (n=55) made from medical-grade polycaprolactone in 11 minipigs for 12 months. Various treatment groups were investigated where immediate or delayed autologous fat graft, as well as platelet rich plasma were added to scaffolds. Computed Tomography and Magnetic Resonance Imaging was performed on explanted scaffolds to determine volume and distribution of regenerated tissue. Histological analysis was performed to confirm tissue type. At 12 months we were able to regenerate and sustain a mean soft tissue volume of 60.9 4.5 ml (95% CI) across all treatment groups. There was no evidence of capsule formation. There were no immediate or long-term post-operative complications. In conclusion, we were able to regenerate clinically relevant soft tissue volumes utilizing SGBTR in a pre-clinical large animal model.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic myelopoietic growth factor and proinflammatory cytokine, clinically used for multiple indications and serving as a promising target for treatment of many disorders, including cancer, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, COVID-19. We have previously shown that dimeric Ca2+-bound forms of S100A6 and S100P proteins, members of the multifunctional S100 protein family, are specific to GM-CSF. To probe selectivity of these interactions, the affinity of recombinant human GM-CSF to dimeric Ca2+-loaded forms of 18 recombinant human S100 proteins was studied by surface plasmon resonance spectroscopy. Of them, only S100A4 protein specifically binds to GM-CSF with equilibrium dissociation constant, Kd, values of 0.3-2 μM, as confirmed by intrinsic fluorescence and chemical crosslinking data. Calcium removal prevents S100A4 binding to GM-CSF, whereas monomerization of S100A4/A6/P proteins disrupts S100A4/A6 interaction with GM-CSF and induces a slight decrease in S100P affinity for GM-CSF. Structural modelling indicates the presence in the GM-CSF molecule of a conserved S100A4/A6/P-binding site, consisting of the residues from its termini, helices I and III, some of which are involved in the interaction with GM-CSF receptors. The predicted involvement of the ‘hinge’ region and F89 residue of S100P in GM-CSF recognition was confirmed by mutagenesis. Examination of S100A4/A6/P ability to affect GM-CSF signaling showed that S100A4/A6 inhibit GM-CSF/S100-induced suppression of viability of monocytic THP-1 cells. The ability of the S100 proteins to modulate GM-CSF activity is relevant to progression of various neoplasms and other diseases, according to bioinformatics analysis. The direct regulation of GM-CSF signaling by extracellular forms of the S100 proteins should be taken into account in the clinical use of GM-CSF and development of the therapeutic interventions targeting GM-CSF or its receptors.

Macrophage-derived chemokine belongs to the CC subfamily. It is produced by dendritic cells (DCs) and macrophages with or without external stimulation. We have previously shown a statistically significant depletion of MDC/CCL22 concentrations in a number of studies concerning COVID-19. These shifts in concentrations demonstrated stability unrelated to the SARS-CoV-2 genetic variant and remained noticeable even in convalescent patients. In this work, we analyze MDC/CCL22 dynamics in various diseases, including those that manifest with inflammation in lung tissue. In addition, we provide our hypothesis on such a decrease in MDC/CCL22 concentrations in COVID-19. If its secretion by producer cells is unperturbed, then it is possible for viral products to bind to this chemokine and to block its functional activity. There is, however, another possible explanation directly linked to depletion in DC subpopulations and the inhibition of their function. We also discuss MDC/CCL22's role in the immunology of novel coronavirus infection, based on both our own data and other studies.

Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy-1, an adhesion molecule integral to fibroblasts, relevant in fibrogenesis and detectable in serum as soluble Thy-1 (sThy-1), is expressed by PMF but not hepatic stellate cells in vitro. This study aimed to elucidate the correlation between Thy-1 expression in liver histology and sThy-1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction associated steatotic liver disease (MASLD). Liver histology samples were stained for Thy-1 and sThy-1 was measured using an enzyme-linked immunosorbent assay (ELISA). In patients with PBC and MASLD, portal Thy-1 expression significantly correlated with increased fibrosis. The sinusoidal Thy-1 expression also significantly correlated with increased fibrosis in patients with PBC (p

In bone tissue engineering, ceramics have been the choice due to their excellent biological properties. But the paradigm changed with the discovery of bioactive glasses (BGs) in 1969 by Larry Hench and co-workers, due to their ability to bond to living tissues through the formation of an interfacial bone-like hydroxyapatite layer when the bioglass was put in contact with biological fluids in vivo. Among a number of tested compositions, the one exhibiting the highest bioactivity index is the well-known trademarked 45S5 Bioglass®. The topic received increasing attention particularly after 1985 when this material entered in the market of biomedical devices, inspiring many other investigations aiming at further exploring the in vitro and in vivo performances of this BG, or developing other related BG compositions. The research efforts gradually revealed a number of shortcomings of 45S5 Bioglass®, mostly derived from its high sodium content, initially intended to decrease the melting temperature and accelerating the degradation of the silicate network over time. But the extensive release of sodium from 45S5 Bioglass® in the biological fluids creates a high pH cytotoxic environment. Other serious drawbacks include a fast degradation rate, and a poor sintering ability, which hinders the reliable fabrication of porous scaffolds. Therefore, sol-gel was regarded as an attractive alternative to prepare alkali-free BG compositions. The process uses inorganic and/or organic precursors, which undergo hydrolysis and condensation at room-temperature, being less costly. When properly conducted, the sol-gel process might result in amorphous structures with all the components intimately mixed at the atomic scale. Moreover, developing new better performing materials for bone tissue engineering is a growing concern, as the ageing of the world’s population leads to lower bone density and osteoporosis. This work describes the sol-gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO2 – 34 CaO – 4 MgO – 2 P2O5 (mol%) was prepared using acidified distilled water as single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The results of XRD of samples calcined within the temperature range from 600-900 ºC demonstrated that amorphous nature was maintained until 800 ºC, followed by partial crystallization at 900 ºC. The specific surface area, an important factor in osteoconduction, was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m2/g at 600 ºC down to 2.2 ± 0.1 m2/g at 900 ºC, being accompanied consistent changes in average pore size and agreeing pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering.

Segmental bone defects caused by trauma, infection, tumor resection or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard to restore function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in incorporation with host bone as well as cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells and urine-derived stem cells for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hopeful in the future that these preclinical results will translate into new therapies for bone defect repair.

The advancements achieved in Tissue Engineering are based on a careful and in-depth study of cell-tissue interaction. The choice of a certain biomaterial in Tissue Engineering is fundamental as it represents an interface for adherent cells in the creation of a microenvironment suitable for cell growth and differentiation. The knowledge of the biochemical and biophysical properties of the extracellular matrix is a useful tool for the optimization of polymeric scaffolds. The aim of this re-view is to analyse the chemical, physical and biological parameters on which it is possible to act in Tissue Engineering for the optimization of polymeric scaffolds. Understanding the scaffold impact on cell fate is of paramount importance for the successful advancement of Tissue Engineering.

Recent research efforts in bone tissue engineering have been primarily directed towards manufacture-viable synthesis of biomaterials that can significantly enhance the biocompatibilities and osteogenic capabilities on the new biomaterials. This paper presents a straightforward, cost-effective, optimized, and well-controlled hydrothermal synthesis of Nb-doped potassium titanate nanofibers in high-purity. Characterization data revealed that the Nb-doping potassium titanate maintained the crystal structure, showing great promise for applications in bone tissue engineering.

Microwave radiation diagnosis technology can detect thermal changes in skin tissue earlier than anatomical changes, but its detection accuracy is limited by non-target radiation interference in the measurement environment, additional measurement errors of system units, and energy scattering and transmission between skin tissues. This paper aims to address the scientific challenges of analyzing the forward and inversion modelling detection mechanism of layered accurate temperature measurement of human skin tissue based on multi-band. The study focuses on the construction of a pencil beam antenna optimization system, the optimization strategy of high-sensitivity correlated radiometer architecture, and the high-precision multi-band forward and inversion modelling detection algorithm. The key technologies include: (1) A new method of integrated modeling and multi-index optimization of antenna with high directivity and small aperture is proposed, and a priori knowledge-guided neural network of pencil beam distribution is constructed to realize the inversion model of antenna structural parameters; (2) The influence mechanism of high sensitivity correlated radiometer architecture error is analyzed, and a periodic phase shift error correction algorithm based on uniform polar circle is designed; (3) Combining deep learning theory and hyperparameter optimization framework, an iterative model is established, and the objective function modified by the penalty factor is defined to realize a new detection method combining forward and inversion. This paper presents a theoretical foundation for the industrialization of microwave radiation diagnostic technology.

An intricate relationship between impaired immune functions and the age-related accumulation of tissue senescent cells (SC) is rapidly emerging. The immune system is unique as it undergoes mutually inclusive and deleterious processes of immunosenescence and cellular senescence with advancing age. While factors inducing immunosenescence and cellular senescence may be shared, however, both these processes are fundamentally different which holistically influence the aging immune system. Immunosenescence is a well-characterized phenomenon, but our understanding and biological impact of cellular senescence in immune cells, especially in the innate immune cells such as macrophages, is only beginning to be understood. Tissue-resident macrophages are long-lived, and while functioning in tissue-specific and niche-specific microenvironments, senescence in macrophages can be directly influenced by senescent host cells which may impact organismal aging. In addition, evidence of age-associated immunometabolic changes as drivers of altered macrophage phenotype and functions such as inflamm-aging is also emerging. The present review describes the emerging impact of cellular senescence vis-à-vis immunosenescence in aging macrophages, its biological relevance with other senescent non-immune cells, and known immunometabolic regulators. Gaps in our present knowledge, as well as strategies aimed at understanding cellular senescence and its therapeutics in the context of macrophages, have been reviewed.

Patients with COVID-19 have coagulation and platelet disorders, with platelet’s alterations and thrombocytopenia representing negative prognostic parameters, being associated with severe forms of the disease, and increase lethality. Methods: Aim of this study was to study expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation Results: a total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19 +), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS CoV-2 (-) negative lungs (COVID-19 -), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1 positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of dead patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocytes over-expression in the lung. Conclusions: microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

This study addresses the urgent need for sustainable protein sources in aquaculture due to the depletion of marine resources and rising costs. Animal protein sources, particularly poultry by-product meal (PBM) and insect exuviae meal, are investigated as viable alternatives to fishmeal (FM). Research confirms the successful replacement of FM with a combination of PBM and insect exuviae meal (up to 50%) in the diet of European seabass without compromising growth, feed conversion, gut health and liver fat content. In particular, growth performance was robust with both PBM formulations, with the 25% PBM diet showing better results. Histological examinations showed good gut and liver health, contradicting the concerns of previous studies. The study emphasizes the importance of holistic analyzes that go beyond growth parameters and include histomorphological investigations. The results show that PBM in combination with insect/exuviae meal is well tolerated by seabass, which is consistent with literature reports of mitigating negative effects on gut health. A detailed analysis of the microbiota revealed a decrease in the Firmicutes/Proteobacteria ratio due to an increase in potentially pathogenic bacteria. However, the formulation containing insect exuviae partially counteracted this effect by preserving the beneficial Lactobacillus and promoting the synthesis of short-chain fatty acids (SCFA), particularly butyrate. Chitin-rich components from insect exuviae were associated with improved gut health, which was supported by increased production of SCFA, which are known for their anti-inflammatory properties. The study concludes that a combination of PBM and insect/exuviae meal can replace up to 50% of FM in the diet of seabass, supporting sustainable aquaculture practices. Despite some changes in the microbiota, the negative effects are mitigated by the addition of insect exuviae, highlighting their potential as a prebiotic to increase fish productivity and contribute to a circular economy in aquaculture.

3.9 million individuals rely on kidney replacement therapy worldwide. They experience height-ened susceptibility to cardiovascular diseases and mortality, alongside an increased risk of in-fections and malignancies, with inflammation being key to explaining this intensified risk. This study utilized semi-targeted metabolomics to explore novel metabolic pathways related to in-flammation in this populations. We collected pre and post-session blood samples of patients who had already undergone one year of chronic hemodialysis. And used liquid chromatography and high resolution mass spectrometry to perform a metabolomic analysis. Afterwards, we employed both univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regulari-zation) to identify metabolites associated with inflammation. In the univariate analysis, in-dole-3-acetaldehyde, 2-ketobutyric acid, and urocanic acid showed statistically significant de-creases in median concentrations in the presence of inflammation. In the multivariate analysis, metabolites positively associated with inflammation include allantoin, taurodeoxycholic acid, norepinephrine, pyroglutamic acid, and L-hydroorotic acid. Conversely, metabolites showing negative associations with inflammation include benzoic acid, indole-3-acetaldehyde, methio-nine, citrulline, alphaketoglutarate, n-acetyl-ornithine and 3-4-dihydroxibenzeneacetic acid. Non inflamed patients exhibit preserved autophagy and reduced mitochondrial dysfunction. Under-standing inflammation in this group hinges on the metabolism of arginine and the urea cycle. Additionally, the microbiota, particularly uricase-producing bacteria and those metabolizing tryptophan, play critical roles.

The article focuses on the galvanic replacement synthesis of Ti-Ni and Zr-Ni metal systems with the "core-shell" structure which are potential precursors for intermetallics. The authors defined the effective synthesis parameters and the formation features of polymetallic systems character-ized by granulometric, phase and elemental composition. The X-ray fluorescence and X-ray phase analysis methods showed that the deposition of nickel on dispersed titanium and zirconium leads to the production of test samples with phase composition representing a mechanical mixture of Ni and Ti, Ni and Zr. The method of X-ray fluorescence analysis showed that the presence of hy-drofluoric acid with a 0.5-1.5 M concentration results in the formation of fixed quantitative ratios of elements in the precipitate, which allows the quantitative composition of dispersed systems "titanium - nickel", "zirconium - nickel" to be regulated within a relatively wide range. Scanning electron microscopy proved that all synthesized systems are characterized by a highly porous structure that follows the titanium and zirconium particle surface contour and the presence of spherical nanoscale subunits on the formed particle surface.

Although initially conceived for high-risk patients who are ineligible for surgical aortic valve replacement (SAVR), transcatheter aortic valve replacement (TAVR) is now recommended in a wider spectrum of indications including young patients. However, as for SAVR, TAVR is also associated with a risk of infectious complications, namely prosthetic valve endocarditis (PVE). As the number of performed TAVR procedure increases, and despite the low incidence of PVE post TAVR, clinicians should be familiar with the associated risk factors and the clinical presentation. Whereas the diagnosis of native valve endocarditis can be straightforward applying the modified Duke criteria, the diagnosis of PVE is more challenging given its atypical symptoms, lower sensitivity of the criteria, and low diagnostic yield of conventional echocardiography. Delay in proper management can be associated with increased morbidity and mortality. Therefore, clinicians should have a high index of suspicion and initiate proper work-up according to the severity of illness, the underlying host, and the local epidemiology of the causative organisms. The most common causative pathogens are Gram-positive bacteria such as S. aureus, coagulase negative staphylococci, Enterococcus spp. and Streptococcus spp. (particularly the viridans group) and, less likely Gram-negative and fungal pathogens. The high prevalence of antimicrobial resistance complicates the choice of therapy. There remain controversies regarding the optimal management strategies including indications for surgical interventions. Surgical assessment is recommended early in the course of illness and surgical intervention should be considered in selected patients. As in other PVE, duration of therapy depends on the isolated pathogen, the host, and the clinical response. Since TAVR is a relatively new procedure, the outcome of TAVR-PVE is yet to be fully understood.

Salivary gland tumors are highly variable in clinical presentation and histology. The World Health Organization (WHO) classifies 22 types of malignant and 11 types of benign tumors of the salivary glands. Diagnosis of salivary gland tumors is based on imaging (ultrasound, magnetic resonance imaging) and fine-needle aspiration biopsy, but the final diagnosis is based on histopathological examination of the removed tumor. In this pilot study, we are testing a new approach to identifying peptide biomarkers in saliva that can be used to diagnose salivary gland tumors. The research material for the peptidomic studies was extracts from washings of neoplastic tissues and healthy tissues (control samples). At the same time, saliva samples from patients and healthy individuals were analysed. The comparison of the peptidome composition of tissue extracts and saliva samples may allow the identification of potential peptide markers of salivary gland tumors in patients' saliva. The peptidome composition extracted from 18 tumor and 18 healthy tissue samples, patient (11 samples) and healthy saliva samples (8 samples) was analysed by LC-MS tandem mass spectrometry. A group of 109 peptides were identified that were present only in the tumor tissue extracts and in the patient saliva samples. Some of the identified peptides were derived from proteins previously suggested as potential biomarkers of salivary gland tumors (ANXA1, BPIFA2, FGB, GAPDH, HSPB1, IGHG1, VIM) or tumors of other tissues or organs (SERPINA1, APOA2, CSTB, GSTP1, S100A8, S100A9, TPI1). Unfortunately, none of the identified peptides were present in all samples analysed. This may be due to the high heterogeneity of this type of cancer. The surprising result was that extracts from tumor tissue did not contain peptides derived from salivary gland-specific proteins (STATH, SMR3B, HTN1, HTN3). These results could suggest that the developing tumor suppresses the production of proteins that are essential components of saliva.

Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk‐reducing salpingo‐oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT alleviated menopausal symptoms in BRCA2 carriers and women who were physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in those with a history of cancer. MBSR, on the other hand, was associated with increased intensity of most menopausal symptoms. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level while their need for extensive measures to optimize their psychological wellbeing is ongoing. Adverse effects of MBSR, which are captured in the present study imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in those women.

Abstract: Giant Cell Arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial-GCA and Large Vessel Vasculitis (LV)-GCA, involving the thoracic aor-ta and its branches. 18F-fluorodeoxyglucose positron emission tomography-computed tomogra-phy (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosis of patients with systemic disease. However, its association with soluble inflammatory markers is still elu-sive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT pos-itive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The Most-Disease-Segment Target-to-Background Ratio (TBRMDS) was calculated for 9 LV-GCA patients, while 12 cranial-GCA and 7 Polymyalgia Rheumatica patients with negative initial PET/CT served as disease controls. Serum macrophage-related cytokines were evaluated by Cytometric Bead Array (CBA). Finally, previously published NMR-metabolomics data acquired at the same blood sampling were associated with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.45 vs. 2.55, p=0.008). The analysis identified 6 serum metabolites, as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group, but not the disease controls. Cytokine levels were not associated with PET/CT activity. Combining with CRP, ESR, and TBRMDS a composite index was generated to depict well the differences between active and inactive systemic LV-GCA (25.45 vs 11.45, p=0.0039). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for the everyday clinical practice.

The gastrointestinal and genitourinary tracts share several similarities. Primarily, these tissues are composed of hollow structures lined by an epithelium through which materials need to flow with the help of peristalsis brought by muscle contraction. In the case of the gastrointestinal tract, solid or liquid food must circulate to be digested and absorbed and the waste products eliminated. In the case of the urinary tract, the urine produced by the kidneys must flow to the bladder, where it is stored until its elimination from the body. Finally, in the case of the vagina, it must allow the evacuation of blood during menstruation, accommodate the male sexual organ during coitus, and is the natural way to birth a child. The present review describes the anatomy, pathologies and treatments of such organs, emphasizing tissue engineering strategies.

Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well-defined in resident physicians and fellows (trainees). We aimed to identify sociodemographic, occupational and community factors associated with SARS-CoV-2 infection among trainees during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in New York City (NYC). In this retrospective cohort study, we administered an electronic survey between June 26 and August 31, 2020 to trainees at the Mount Sinai Health System in NYC to assess risk factors for SARS-CoV-2 infection between February 1 and June 30, 2020. We used Bayesian generalized linear mixed effect regression and structural equation models to examine associations. SAR-CoV-2 infection was determined by self-reported IgG antibody and reverse transcriptase-polymerase chain reaction results and confirmed with laboratory results. Among 2354 trainees invited to participate, 328 (14%) completed the survey and reported test results. The cumulative incidence of SARS-CoV-2 infection was 20.1%. Assignment to medical-surgical units (odds ratio [OR], 2.51; 95% CI, 1.18-5.34), and training in emergency medicine, critical care and anesthesiology (OR, 2.93; 95% CI, 1.24-6.92) were independently associated with infection. Deployment to care for unfamiliar patient populations was protective against infection (OR, 0.16; 95% CI, 0.03-0.73). Community factors were not significantly associated with infection after adjustment for occupational factors. Our findings may inform tailored infection prevention strategies for trainees responding to the COVID-19 pandemic.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce retinal detachment to perform the subretinal placement of the transplanted cell; and (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

Uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which are directly associated to their functions. Considering this, application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. Decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed ECM composition and structure by optical and scanning electronic microscopy, FTIR and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting significative reduction of cellular content. Structural and spectroscopy analyses revealed that produced scaffolds remained well structured and with ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing cell survival and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

Nanostructured lipid carriers (NLC) are typically composed of liquid lipids, solid lipids, and surfactants, enabling the encapsulation of lipophilic drugs. Butamben is a Class II anesthetic drug according to the Biopharmaceutical Classification System (BCS), it has a log P 2.87 and is considered a 'brick dust' (poorly water-soluble and poorly lipid-soluble) drug. This characteristic poses a challenge for the development of NLCs, as they are not soluble in the liquid lipid present in the NLC core. In a previous study [1] we have developed a NLC core consisting of solid lipid (CrodamolTM CP), liquid lipid of medium polarity (SRTM Lauryl lactate), and a hydrophilic excipient (SRTM DMI) that allowed the solubilization of 'brick dust' type of drugs including butamben. In this study, starting from the NLC core formulation previously developed we carried out the optimization of the surfactant system and evaluated their performance in aqueous medium. Three different surfactants (CrodasolTM HS HP, SynperonicTM PE/F68, and CroduretTM 40) were studied and, for each of them, a 2³ factorial design was stablished, with total lipids, % surfactant, and sonication time (min) as the input variables and particle size (nm), polydispersity index (PDI) and zeta potential (mV) as the response variables. Stable NLCs were obtained using CrodasolTM HS HP and SynperonicTM PE/F68 as surfactants. Through a comparison between NLCs developed with and without SRTM DMI, it was observed that besides helping the solubilization of butamben in the NLC core, this excipient helped stabilizing the system and decreasing particle size NLCs containing CrodasolTM HS HP and SynperonicTM PE/F68 presented particle size values in the nanometric scale, PDI lower than 0.3 and zeta potential above |10|mV. Concerning NLCs stability, SBTB-NLC with SynperonicTM PE/F68 and butamben demonstrated stability over a 3-month period in aqueous medium. The remaining NLCs showed phase separation or precipitation during the 3-month analysis. Nevertheless, these formulations could be freeze-dried after preparation, which would avoid precipitation in aqueous medium.

The Single Site Order – a policy restricting staff from working at multiple long-term care homes – was mandated by the Public Health Agency of Canada to control the spread of COVID-19 in long-term care homes, where nearly 70% of COVID-19-related deaths in Canada occurred. This mixed methods study assesses the impact of Single Site Order on long-term care residents in British Columbia. Interviews were conducted (residents (n=6), family members (n=9), staff (n=18), and leadership (n=10) from long-term care homes (n=4)) and analyzed using thematic analysis. Administrative data was collected between April 2019 – March 2020 and April 2020 – March 2021 and analyzed using descriptive statistics and data visualization. Qualitative and quantitative data were triangulated and demonstrate staffing challenges became worse during implementation of the SSO resulting in the mental and physical health deterioration of LTC residents. Qualitative data demonstrated decreased time for personalized and proactive care, increased communication challenges, and increased loneliness and isolation. Quantitative data showed a decline in activities of daily living, increased antipsychotic medication use, pressure ulcers, behavioural symptoms, and an increase in falls. Addressing staff workload and staffing shortages during SSO-related policy implementation is essential to avoid resident health deterioration.

Dispersal represents a key life-history trait with several implications for the fitness of organisms, population dynamics and resilience, local adaptation, meta-population dynamics, range shifting and biological invasions. Plastic and evolutionary changes of dispersal traits have been intensively studied over the past decades in entomology, in particular in wing-dimorphic insects for which literature reviews are available. Importantly, dispersal polymorphism also exists in wing-monomorphic and wingless insects, and except for butterflies, fewer syntheses are available. In this perspective, by integrating the very last research in the fast moving field of insect dispersal ecology, this review article provides an overview of our current knowledge of dispersal polymorphism in insects. After having provided a definition of the main terms characterising insects’ movements, some of the most often used experimental methodologies for the separation of dispersers and residents in wing-monomorphic and wingless insects are presented. The existing knowledge on the morphological and life-history trait differences between resident and disperser phenotypes is then synthetized. The fourth part examines the effects of range expansion on dispersal traits and performance, in particular for insects from range edges and invasion fronts. Finally, some research perspectives are proposed in the last part of the review.

Female gynecological organ dysfunction can cause infertility and psychological distress, decreasing quality of life of affected women. Incidence is constantly increasing due to growing rates of cancer and delaying of childbearing age in the developed world. Current treatments are often unable to restore organ function, and occasionally are the cause for female infertility. Alternative treatment options are currently being developed in order to face the inadequacy of current practices. In this review, pathologies and current treatments of gynecological organs (ovaries, uterus, and vagina) will be described. The state-of-the-art of tissue engineering alternatives to common practices are evaluated with a focus on in vivo models. Tissue engineering is an ever-expanding field, integrating various domains of modern science to create sophisticated tissue substitutes in the hopes of repairing or replacing dysfunctional organs using autologous cells. Application to gynecology has the potential of restoring female fertility and sexual wellbeing.

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were submitted to a control diet or a HFD for 16 weeks, treated (or not) with FO for the last 8 weeks. WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with Leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR and Western Blot assays. Mice receiving HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. The study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the leptin-rich environment of obese WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.

A recently published article posited the use of polymer matrix composites (PMCs) as a replacement material for low-carbon steel (LCS) in large power transformer (LPT) tanks [1]. PMCs offer potential advantages such as weight reduction, corrosion prevention, and self-healing of the tank material which may not be achievable with traditional LCS. LCS can arrest ballistic projectiles at relatively low velocities, but at higher velocities, penetration can occur leading to a potential major transformer failure. Numerical simulations of steel projectile impacts upon LCS plates and glass and/or carbon fiber polymer composite laminates showed that with sufficient thickness both could prevent projectile penetration. This prevention was especially efficient when the plates were coated with a high strain rate sensitive material such as polyurea (PU). Our simulations show that the addition of a 3 mm coating of PU to a standard 10 mm thick LCS plate used in LPT tanks could prevent penetration of a 400 m/s steel projectile. For PMC plates, the simulations with the same projectile velocity showed three times faster deceleration with a 3 mm PU coating than without the coating. Thus, two realistic approaches to improving the ballistic protection of LPTs are presented. In addition to their other advantages, this research clearly shows that PMCs with the coating could provide significant ballistic protection for the next generation of LPT tanks.

Purpose: Hormone Replacement Therapy (HRT), an FDA-approved treatment for menopausal conditions was found to be associated with increased risk of endometrial cancer and reduced oestrogen. Studies showing benefits of HRT in preventing chronic diseases lead to development of clinical guidelines by American College of Physicians. This study aims to assess effectiveness of HRT treatments across cardiometabolic measures including Triglycerides (TG), Follicle-Stimulating Hormone, LDL cholesterol, HDL cholesterol, and Estradiol in menopausal women. It reports gaps in scientific knowledge and clinical practice to enhance current guidelines and policies.Methods: A systematic methodology designed and published in PROSPERO (CRD42022346057) to report network meta-epidemiology analysis was utilised. We used databases by PubMed, Web of Science, ScienceDirect, EMBASE and MEDLINE for studies published between 30th of April 1980-2022. Effects of HRT treatments were explored using a mixed treatment comparison (MTC) model. Fixed and random-effects models were used to address heterogeneity in published studies. Publication bias was assessed and corrected using funnel plots and Egger’s test.Results: Of 45 eligible studies, our findings indicate a significant statistical heterogeneity between HRTs and reduction of TG, SFH, LDL-C alongside increase of HDL-C and Estradiol among menopausal women. The analysis suggests a lack of direct evidence to support their efficacy in reducing TG, SFH and LDL-C levels or to substantiate HRT’s effectiveness in increasing HDL-C and Estradiol. The results showed no significant publication bias in the meta-analysis of included studies.Conclusion: Our findings demonstrate that use of HRT interventions among menopausal women may reduce TG, FSH and LDL-C levels and increase levels of HDL-C and estradiol via oral and oral + transdermal administration. Our study reaffirms efficacy of HRT in supporting favourable lipid profile in menopausal women whilst highlighting the need for robust and inclusive epidemiology studies and clinical trials to further develop clinical guidelines and policies.

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that contributes to the progression of several cancers. MIF overexpression has been reported in head and neck squamous cell carcinoma (HNSCC) patients. However, the exact role of MIF in HNSCC is not fully understood. Our aim was to evaluate the amount of secreted MIF and the role of MIF in the proliferation, cell cycle, and apoptosis in HNSCC cell lines. The MIF levels in conditioned media from human primary (HN18 and HN30) and metastatic (HN17 and HN31) HNSCC cell lines were evaluated using ELISA. The HNSCC cell lines were treated with recombinant MIF and its effect on proliferation, cell cycle, and apoptotic status was determined by MTT and flow cytometry, respectively. The HNSCC-secreted MIF concentration ranged from 49.33‒860 pg/ml. Exogenous MIF (25 ng/ml) significantly increased HN18, HN30, and HN31 cell proliferation. Moreover, MIF induced cell cycle progression and inhibited apoptosis in these cells. However, MIF did not affect growth or apoptosis in HN17 cell. In conclusion, the HNSCC cell lines were evaluated secrete MIF. Exogenous MIF promotes various effects on proliferation, cell cycle, and apoptosis in HNSCC cells.