Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

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.

In volleyball, the jump serve is a fundamental and crucial skill that is one of the most commonly used serving techniques. This study aimed to examine the kinematic differences between straight line (SL) and diagonal line (DL) in volleyball jump serves by focusing on torso and attack arm joint motions. Three-dimensional coordinate data were captured using a motion capture system (200 Hz) in 14 right-handed male professional volleyball players who performed SL and DL jump serves. This result suggests that the pelvis and torso backward rotation angles during the arm-clocking phase were smaller when performing DL serves. During ball contact, the servers exhibited greater forward rotation angles of the pelvis and torso to control the upper body facing the diagonal direction of the target zone. In addition, lowering the forward tilt angle of the trunk helped the servers maintain body balance in the air and increased their wrist flexion angle, preventing the ball from flying out of bounds when performing DL. These findings highlight the importance of controlling pelvic and torso rotations in the transverse plane when adjusting for different serving lines. These insights can guide volleyball athletes and coaches in refining their serving techniques.

The enormous potential of renewable bioresources is expected to play a key role in the development of the EU’s sustainable circular economy. In this context, inexhaustible, biodegradable, non-toxic and carbon-neutral forest-origin resources are very attractive for the development of novel sustainable products. The main structural component of wood is cellulose, which, in turn, is the feedstock of nanocellulose, one of the most explored nanomaterials. Different applications of nanocellulose have been proposed, including packaging, functional coatings, insulating materials, nanocomposite fields among others. However, the intrinsic flammability of nanocellulose restricts its use in some industries where fire risk is a concern. This paper overviews the most recent studies of the fire resistance of nanocellulose-based materials, focusing on thin films, coatings and aerogels. Along with effectiveness, increased attention to sustainable approaches is considered in developing novel fire-resistant coatings. The great potential of bio-based fire-resistant materials, combined with conventional non-halogenated fire retardants FRs, has been established. The formulation methods, types of fire retardants and their action modes, and methods used for analysing fire retardancy are discussed in the frame of this overview.

There has been no significant efficacy in treatment for osteosarcoma (OS) metastasis after nearly four decades of trials. This motivates us to elucidate OS therapies according to their four bidirectional mutation stages. To refresh the OS therapy status quo, the historical developments and clinical advancements are briefly described. However, the main issue of metastasis remains unresolved, accounting for 90% of pulmonary metastasis deaths. Thus, this metastasis problem is related to immune evasion and chemoresistance that are being induced after long-term treatment by the use of immunotherapy for tumorigenesis. Therefore, it is rationale to discuss the relationship cycles of mutation stages including tumorigenesis, metastasis, immune evasion, and chemoresistance. Even though many combinational and targeted therapies have been developed to intensify these mutation treatments, successful clinical translations with higher cure rates are still rare. Through this review, an in-depth understanding of the bidirectional relationship between the four OS mutation stages and their respective therapies is provided. Herein, we summarise the medicines used to treat tumorigenesis, including COLGALT2 inhibitors, Tra2B, and AGAP1, miR-148a and miR-21-5p EVs, and the lncRNA LIFR-AS1. Following the medicines used to treat metastasis are AXL, miR-135a-5p, mRNA BCL6, TGFβ1, Tim-3, SOCS5, CASC15, KLF3-AS1, PDCD4, ATG5, and Rab22a-NeoF1. Then the medicines used to treat immune evasion are N-cadherin, anti-IL-9, USP12 inhibitor, IgG-4+ B-cells, LAP inhibitor, anti-Wnt2 mAb, anti-αvβ8 integrin, HK2-mediated IκBα, IDO inhibitor with NO, and TGF-βRII with anti-IgG1. Finally, the medicines used to treat chemoresistance are DHFR, FPGS, HSP-90AA1, XCT-790, ATKI, and IGF1. As a result, this contribution is expected to serve as a reference and guide for scientists and clinicians.

A large core size and bending resistance are very important properties of mid-infrared energy transfer fibers, but large core sizes usually lead to a deterioration of bending properties. A negative-curvature nested node-free anti-resonant hollow-core fiber (AR-HCF) based on quartz is proposed. It was made by adding a nested layer to a previous AR-HCF design to provide an additional anti-resonance region while keeping the gap between adjacent tubes strictly correlated to the core diameter to produce a node-free structure. These features improve the fiber’s bending resistance while achieving a larger core diameter. The simulation results show that the radial air-glass anti-resonant layer is increased by the introduction of the nested anti-resonant tube, and the weak interference overlap between the fiber core and the cladding mode is reduced, so the fiber core’s limiting loss and the sensitivity to bending are effectively reduced. When the capillary wall thickness t of the fiber is 0.71 μm, the core diameter D is 70 μm, the ratio of the inner diameter of the cladding capillary to the core diameter d/D is 0.62, and the diameter of the nested tube is d0=29 μm, the fiber has a lower limiting loss at the wavelength of 2.79 μm, and the limiting loss is 3.28×10-4 dB/m. At the same time, the optimized structure also has good bending resistance. When the bending radius is 30 mm, the bending loss is only 4.72×10-2 dB/m. To our knowledge, this is the first research to achieve an anti-bending low-loss micro-structure hollow fiber with a bending radius of less than 30 mm in the 2.79 μm band. An anti-bending low-loss anti-resonant hollow-core fiber with this structure constitutes a reliable choice for the light guiding system of a 2.79 μm band erbium laser therapy instrument.

Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, are often attributed to late stage at diagnosis and relapse following chemotherapy. HGS ovarian cancer is a heterogenous disease in that few genes are consistently mutated between patients. Additionally, HGS ovarian cancer is characterized by high genomic instability. For these reasons personalized approaches may be necessary for effective treatment and cure. Understanding the molecular mechanisms that contribute to tumor metastasis and chemoresistance are essential to improve survival rates. One favored model for tumor metastasis and chemoresistance is the cancer stem cell (CSC) model. CSCs are cells with enhanced self-renewal properties that are enriched following chemotherapy. Elimination of this cell population is thought to be a mechanism to increase therapeutic response. Therefore, accurate identification of stem cell populations that are most clinically relevant is necessary. While many CSC identifiers (ALDH, OCT4, CD133, and side population) have been established, it is still not clear which population(s) will be most beneficial to targeted in patients. Therefore, there is a critical need to characterize CSCs with reliable markers and find their weaknesses that will make the CSCs amenable to therapy. Many signaling pathways are implicated for their roles in CSC initiation and maintenance. Therapeutically targeting pathways needed for CSC initiation or maintenance may be an effective way of treating HGS ovarian cancer patients. In conclusion, the prognosis for HGS ovarian cancer may be improved by combining CSC phenotyping with targeted therapies for pathways involved in CSC maintenance.

Cancer cells utilize a number of mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm and epigenetic regulation by microRNAs (miRNAs). Due to the fact that it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced and the cancer cells may have acquired drug resistance. This review summarizes the main mechanisms involved in cisplatin resistance and in interactions between cisplatin-resistant cancer cells and the tumor microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin resistant non–small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly-dysregulated TP53, MDM2 and CDKN1A genes as they encodes the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

Sepsis is a serious disease that can lead to mortality. The etiology of the disease is connected to how the body as a host reacts toward microbes such as bacteria, viruses, and fungi invasion. Current research shows that during sepsis, the reaction toward microbe attacks takes two main phases. The first is known as a cytokine storm, while the second is a vicious cycle of pro-inflammatory responses followed by a strict anti-inflammatory response led by CD4+ Tregs. Various immunomodulatory therapies have been proposed to break the cycle of pro- and anti-inflammatory reactions to sepsis. However, clinical trials did not show promising results, indicating further research into the mechanism that Treg uses to inhibit proinflammatory reactions. We used next-generation sequencing (NGS) analysis of bulk RNA-seq and single-cell RNA-seq data to examine the exact molecular pathways used by Treg to inhibit the immune response in sepsis. Our approach identified ACOD1 (Aconitate Decarboxylase 1) as a primary mediator of Treg suppression of immune cells. We identified and validated CD36 as a downstream target of ACOD1. CD36 is a known metabolite regulator in Tregs. Taken together, our results indicate that targeting ACOD1 could prove valuable in regulating Treg function during sepsis.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

Currently, in some domestic and foreign mines, the backfill drilling pipeline experience a rupture phenomenon even when the wear degree is low. This results in a delay in production due to the filling becoming 'sick'. This paper presents, for the first time, the damage mechanism from a mechanical perspective and re-derives the anti-extrusion strength model of the backfill drilling pipeline. We investigate the influence of law on the anti-extrusion strength of pipelines from the perspective of stratum and cement ring. We then verify the theoretical and simulation results through engineering examples. The results demonstrate that the Mises stress criterion is a suitable modification principle for the anti-extrusion strength model of the backfill drilling pipeline. The anti-extrusion strength of the pipeline is related to the elastic modulus and Poisson's ratio of the stratum, and the thickness of the cement ring. It is negatively affected by the depth of the stratum. For hard strata, a cement ring with a smaller elastic modulus is suitable, while for soft stratum, a cement ring with a larger elastic modulus is recommended. When the missing angle of the cement ring is less than 60°, the stress concentration factor increases up to 2.2. The stress unloading capacity of the cement ring ranges from 32.7% to 37.8%, and optimal performance of the cement ring is achieved when it has high strength and low rigidity. The backfill filling pipeline of a copper mine abroad was destroyed due to external extrusion force exceeding its anti-extrusion strength value. The modified pipeline anti-extrusion strength model is 18.2% higher than the casing API strength value. This finding can inform the design of the backfill filling pipeline for China's kilometer-deep wells in the future.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In our study we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of oral cancer compared to normal tissues. The downregulation of NGAL was strongly correlated with the degree of differentiation and stage (I-IV), and can serve as a prognostic biomarker for oral cancer. Tobacco carcinogens were also found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased oral cancer cell proliferation, survival, and migration, and also induced resistance against cisplatin. Silencing of NGAL activated mTOR signaling and reduced autophagy by the LKB1-AMPK-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and MMP-9 were upregulated, and caspase-9 was downregulated, suggesting that silencing of NGAL increases oral cancer cell proliferation, survival, and migration. Thus, from our study it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of oral cancer.

Encephalitis is a condition with a variety of etiologies, clinical presentations and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), ⍺-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process.

In this follow-up study, we aimed to assess the effectiveness of the “I do not smoke, I exercise”, anti-smoking preventive health education program. The program was based on the Theory of Planned Behavior supplemented with life-skills teaching and targeted at high school students. The intervention comprised ten one-hour online sessions, administered by physical education instructors. The study cohort comprised 222 students (109 boys, 113 girls) from 11 secondary schools, with an average age of 16.42 ± 1.36 years. Data collection involved pre- and post-intervention self-assessment questionnaires. The examined variables included attitudes towards smoking, intention to smoke, subjective norm, perceived behavioral control (PBC), knowledge about smoking, smoking behavior, exercise behavior, attitudes toward the program's implementation, and satisfaction with the program. Separate paired samples t-test revealed a significant improvement in students' knowledge about smoking, perceived behavioral control, and overall program satisfaction following the intervention. However, no significant changes were observed in the remaining variables. These findings suggest that the health education smoking prevention intervention incorporates techniques and strategies that influence the Perceived Behavioral Control variable, emphasizing students' strong interest in educationally theorized programs integrating technology into their design. Future studies should consider further examination of tobacco control strategies within the high school context.

The review explores the therapeutic potential of mangrove plants as sources of bioactive compounds, particularly focusing on their anti-inflammatory properties. Mangroves, found in tropical and sub-tropical tidal coasts, exhibit unique ecological and biological activities. The review compiles and examines 136 research findings published between 1982 and 2018, with 41 studies specifically addressing the anti-inflammatory properties of mangroves in Indian coastal regions, including the Andaman and Nicobar Islands. It summarizes the chemical structures, molecular weights, formulas, solvents, and biological activities of these mangroves, as reported by various researchers over time. The data underscore the significant potential of tropical Indian mangroves in anti-inflammatory applications. However, a notable research gap exists regarding the extraction of bioactive compounds from mangrove species in the Andaman and Nicobar Islands compared to other regions such as Gujarat, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, Odisha, West Bengal, and Puducherry. Overall, the compilation provides valuable insights into mangrove-based studies for drug discovery research, emphasizing the need for further exploration and exploitation of these natural resources.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

The aim of this study was to investigate the physicochemical characterization and biological activities of chitosan (CH) based composite films with the incorporation of chestnut flower essential oil (CFEO). The composite films were prepared by casting method and characterized in terms of structural, morphological and mechanical properties via FT-IR, XRD, UV, SEM and TGA. The results proved the significantly increased water vapor permeability (WVP), heat resistance, antibacterial and antioxidant capabilities of CH-CFEO films. The incorporation of CH and CFEO enhanced the UV blocking, which made the film shield almost all UV light. Films with the tensile strength of 6.37 ± 0.41 MPa and elongation at break of 22.57 ± 0.35% were got with 6 mg mL-1 CFEO. Subsequently, the fruit preservation experiments also confirmed that the composite films could effectively extend the shelf life of bananas through their excellent water vapor and oxygen barrier. These desirable performances enable our newly developed composite films to be a remarkable packaging material to solve the fresh fruit preservation dilemma.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

Monitoring of clients living with HIV encompasses a specific array of activities that routinely check on various aspects of ART following its initiation depending on the availability of resources in that particular state, among other factors as per guidelines from the World Health Organisation. This is a significant practice as it promotes positive health outcomes for patients and efficient utilisation of ART regimens to reduce resistance to the medication – hence it is a measure to guard avoidable costs. It also forms a basis on which decisions are made from. It can be done clinically by assessing for signs e.g., skin rash and symptoms e.g., nausea and vomiting, checking vital organ function and measuring weights across all populations, or can be also be done by assessing specimens for their respective viral loads, white blood cell count, pregnancy status or other infections such as hepatitis B. There have not been any special indications required for one to be eligible for monitoring during ART in developing countries; all qualify for routine monitoring even though some may be more frequent than others in cases of comorbidities such as renal failure where medications can be attributed to exacerbating the condition.

Leishmaniasis are neglected diseases that affect regions such as South Asia, South Africa and Latin America, less developed regions. Current treatment, for cutaneous, mucocutaneous and visceral leishmaniosis, which are the main forms of the disease, is based on the administration of pentavalent antimonial and amphotericin B. However, these drugs have low efficacy and high toxicity. For this reason, the search for new treatments for this disease is necessary, based on studies of new molecules and their conformations. The research proposed the conformational study of brominated guanidine compounds with potential antileishmanial activity using Nuclear Magnetic Resonance (NMR) and X-ray diffraction (XRD) techniques. The present study involves the bro-minated molecules, LQOF-G2, LQOF-G30, LQOF-G35 and LQOF-G35-Br. The later was synthesized by the reaction of LQOF-G35 with NBS under IR irradiation at 120 Watts of potency and dichloro-methane as solvent by 12-h of exposition. The obtained results demonstrated the efficiency of the bromination method, since two bromines atoms entered the molecule. Furthermore, NMR analysis showed the occurrence of a conformational change from Z to E when compound LQOF-G35 was brominated to LQOF-G35-Br. This feature was well confirmed by comparative DRX study of the LQOF-G35 and LQOF-G35-Br compounds. The antileishmanial activity of LQOF-G2 e LQOF-G35 motivated the synthesis of new brominated compounds LQOF-G30 e LQOF-G35-Br.

The main inhibitory neurotransmitter in the mammalian brain is 4-aminobutyric acid (GABA). Phthalimide acts as a sodium channel antagonist, one of the finest targets for treating epilepsy is the sodium channel and JNK kinase activity is inhibited to treat epilepsy. a novel compound with multiple targets of action for the treatment of epilepsy also anti-oxidant activity has been designed. The compounds are designed in two series aldehydes and aniline. Docking of all the designed compounds has been done with the suitable protein GABA-AT, sodium channel, JNK protein, and anti-oxidant from protein bank. QSAR was done for constructing many linear regression models. In combination with the developed Docking and QSAR outcomes, ADMET has been performed for the active compounds. The result shows that 11 of the compounds have excellent binding energy in docking with all the receptors and also have good QSAR results and follow the ADMET. The structural understanding of human GABA-AT inhibition was obtained from molecular dynamics simulation studies for compound no. 11 at 5 nanoseconds. Synthesis and pharmacological activity also suggest that the designed compound no.11 be considered the best Novel Compound.

Chronic myeloid leukemia (CML) is the most common form of leukemia in adults and accounts for approximately 15% of all leukemia cases. The etiology of this disease is based on the presence of the oncogenic Bcr/Abl fusion protein, which has dysregulated tyrosine kinase activity. This pathological condition is the result of a chromosomal translocation between chromosomes 9 and 22 leading to the formation of the Philadelphia chromosome (Ph). Clinical establishment of targeted therapy with Abl kinase inhibitors (AKIs) has been observed in the treatment of CML. Therapy resistance in patients with CML is due to genetic alterations in the cells of CML, specifically affecting the Bcr/Abl oncoprotein. Acquired resistance of CML patients to tyrosine kinase inhibitors (AKIs) has also been associated with the tumor microenvironment (TME). This study aimed to examine the role of hypoxic conditions in the development of chemoresistance to certain AKIs in CML. The findings of our study indicate that exposure to hypoxic conditions leads to a substantial increase in chemoresistance to crizotinib, while only resulting in a slight increase in chemoresistance to imatinib. It is worth noting that both drugs effectively block Bcr/Abl function. Furthermore, it was observed that the inclusion of the JAK1/2 inhibitor ruxolitinib resulted in an augmentation of chemoresistance to crizotinib in the context of hypoxia. Overexpression of hypoxia-inducible factor 1a (HIF1a) and silencing of JAK2 confirmed that the two proteins cooperate in mediating chemoresistance to crizotinib in CML cell lines. It is noteworthy that the compound 2-methoxy estradiol (2ME2), which is a metabolite of estradiol lacking estrogenic activity, has shown efficacy in reinstating the sensitivity of CML cells to crizotinib in the presence of hypoxic circumstances. Additionally, when used in conjunction with a JAK2 inhibitor, 2ME2 exhibited activity in restoring crizotinib sensitivity in CML cells. The findings of our study underscore the significance of selectively targeting elements of the HIF1α pathway in order to achieve total eradication of chronic myeloid leukemia (CML) cells.

Chronic myeloid leukemia (CML) is the most common form of leukemia in adults and accounts for approximately 15% of all leukemia cases. The etiology of this disease is based on the presence of the oncogenic Bcr/Abl fusion protein, which has dysregulated tyrosine kinase activity. This pathological condition is the result of a chromosomal translocation between chromosomes 9 and 22 leading to the formation of the Philadelphia chromosome (Ph). Clinical establishment of targeted therapy with Abl kinase inhibitors (AKIs) has been observed in the treatment of CML. Therapy resistance in patients with CML is due to genetic alterations in the cells of CML, specifically affecting the Bcr/Abl oncoprotein. Acquired resistance of CML patients to tyrosine kinase inhibitors (AKIs) has also been associated with the tumor microenvironment (TME). This study aimed to examine the role of hypoxic conditions in the development of chemoresistance to certain AKIs in CML. The findings of our study indicate that exposure to hypoxic conditions leads to a substantial increase in chemoresistance to crizotinib, while only resulting in a slight increase in chemoresistance to imatinib. It is worth noting that both drugs effectively block Bcr/Abl function. Furthermore, it was observed that the inclusion of the JAK1/2 inhibitor ruxolitinib resulted in an augmentation of chemoresistance to crizotinib in the context of hypoxia. Overexpression of hypoxia-inducible factor 1 (HIF1) and silencing of JAK2 confirmed that the two proteins cooperate in mediating chemoresistance to crizotinib in CML cell lines. It is noteworthy that the compound 2-methoxy estradiol (2ME2), which is a metabolite of estradiol lacking estrogenic activity, has shown efficacy in reinstating the sensitivity of CML cells to crizotinib in the presence of hypoxic circumstances. Additionally, when used in conjunction with a JAK2 inhibitor, 2ME2 exhibited activity in restoring crizotinib sensitivity in CML cells. The findings of our study underscore the significance of selectively targeting elements of the HIF1α pathway in order to achieve total eradication of chronic myeloid leukemia (CML) cells.

Intelligent fault diagnosis techniques have replaced the time-consuming and unreliable human analysis, increasing the efficiency of fault diagnosis. Deep learning model can improve the accuracy of intelligent fault diagnosis with the help of its multilayer nonlinear mapping ability. This paper has proposed a novel method named Deep Convolutional Neural Networks with Wide First-layer Kernels (WDCNN). The proposed method uses raw vibration signals as input (data augmentation is used to generate more inputs), and uses the wide kernels in first convolutional layer for extracting feature and suppressing high frequency noise. Small convolutional kernels in the preceding layers are used for multilayer nonlinear mapping. AdaBN is implemented to improve the domain adaptation ability of the model. The proposed model addresses the problem that currently, the accuracy of CNN applied to fault diagnosis is not very high. WDCNN can not only achieve 100% classification accuracy on normal signals, but also outperform state of the art DNN model which is based on frequency features under different working load and noisy environment.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from 33 strains (including 20 dinoflagellates, 4 diatoms and 9 strains from other 7 algal classes), cultivated under identical conditions were examined for antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Wide differences were observed between species within the same class, in particular dinoflagellates which were better represented in this study. These preliminary findings pave the way for in-depth characterization of extracts with highest signals in each test, identification of compounds responsible of the biological activities found, and a further screening of the CCVIEO culture collection.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella-zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKi), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. In twenty-four RA patients with new-onset HZ and forty-two without HZ, serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ inducible protein-10 (IP-10) were measured by ELISA. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21pg/ml, interquartile range (IQR) 77.63-150.30pg/ml versus 142.3pg/ml, IQR 106.7-175.6pg/ml, p<0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8ng/ml, IQR 21.0-38.2ng/ml versus 10.5ng/ml, IQR 9.9-15.0ng/ml, p<0.005). In conclusion, patients with HZ had significantly lower MCP-1 levels than those without HZ, and patients with severe HZ had significantly higher titers of anti-IFN-γ than those with non-severe HZ. Given small sample size, our results need further validation in future studies.

Enterococcus faecalis is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04 (ФKEN04), isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR Enterococcus faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between -80ᵒC and 37ᵒC. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G+C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that ФKEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.

The thesis proposes a argument that a mass point moving in a horizontal circle on the Earth's surface can generate a radial centrifugal force of the Earth's center of mass, thus realizing an unconventional anti-gravity path. And through the theoretical analysis of the difference in the distribution of gravitational acceleration at different latitudes caused by the rotation of the earth, and the centrifugal force of a mass point moving in a horizontal circle on the earth's surface is analyzed, the validity of the argument is demonstrated. At the same time, the paper puts forward two possible basic principles, and makes theoretical analysis and demonstration. Conceive of the concrete experimental verification of principle two is proposed. Four technical schemes for antigravity ascent are proposed and basic analysis is made. On the premise of not fully considering the practical technical ability, it is theoretically proved that three of them have realistic operability and development potential. In theory, this paper opens up a different way of anti-gravity for human beings, which will bring new ideas and prospects for human beings to get rid of the bondage of gravity.

Cellulose nanocrystals (CNCs) are cellulose-derived nanomaterials that can be easily obtained, e.g., from vegetable wastes produced by circular economies. They show promising antimicrobial activity and the absence of side effects and toxicity. This study investigated the ability of CNCs to reduce microbial adherence and biofilm formation using in vitro microbiological models reproducing the oral environment. Microbial adherence by microbial strains of oral interest, Streptococcus mutans and Candida albicans was evaluated on the surfaces of salivary pellicle-coated enamel disks in the presence of different aqueous solutions of CNCs. The antibiofilm activity of the same CNC solutions was tested against S. mutans and an oral microcosm model based on mixed plaque inoculum using a continuous-flow bioreactor. Results showed an excellent anti-adherent activity of the CNCs against the tested strains from the lowest concentration tested (0.032 wt.%). Such activity was significantly higher against S. mutans than C. albicans, suggesting a selective anti-adherent activity against pathogenic strains. At the same time, there was a minimal albeit significant antibiofilm activity (at least 0.5 and 4 wt.% CNC solution for S. mutans and oral microcosm, respectively). This makes CNCs particularly interesting as anticaries agents, encouraging their use in the oral field.

Counterfeiting and theft have always been problems that incur high costs and results in considerable losses for the international markets. In this research paper, we will address the issue of counterfeiting while using RFID technology in retailer systems or other industries by presenting a new anti-counterfeiting and anti-theft system for the retailer market. This system will address the two above mentioned issues and provide a solution that can save the retailer systems millions of dollars yearly. This proposed system will achieve the objective of preventing or minimising the counterfeiting and theft of tagged products. At the same time, it will provide a strong indication for suspiciously sold or obtained items. Furthermore, we conducted a security analysis to prove the correctness of our protocol on the basis of the strand spaces.

CD44 is a type I transmembrane glycoprotein, which is associated with poor prognosis in various solid tumors. Since CD44 plays critical roles in tumor development by regulating cell adhesion, survival, proliferation, and stemness, it has been considered a target for tumor therapy. Anti-CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody-drug conjugates and chimeric antigen receptor-T cell therapy. We previously developed anti‐pan-CD44 mAbs, C₄₄Mab-5 and C₄₄Mab-46, which can recognize both CD44 standard (CD44s) and variant isoforms. In the present study, a defucosylated mouse IgG_2a version of the anti-pan-CD44 mAbs (5-mG_2a-f and C₄₄Mab-46-mG_2a-f) was generated to evaluate the antitumor activities against CD44-positive cells. Both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f recognized CD44s-overexpressed CHO-K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could activate effector cells in the presence of CHO/CD44s cells and exhibited the complement‐dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5-mG_2a-f and C₄₄Mab-46-mG_2a-f significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control defucosylated mouse IgG_2a. These results indicate that 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could exert antitumor activities against CD44-positive cancers and could be a promising therapeutic regimen for tumors.

The presence of anti SARS-CoV2-RBD antibody (Anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care Anti-RBD test implemented in person living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 persons with comorbid (PLWH, SLE, CKD) to test anti-RBD assay compared to surrogate viral neutralization (SVNT) as the reference test. We performed linear correlation analysis between anti-RBD vs SVNT and a ROC analyses to ascertain anti-RBD cut-off at 30%, 60%, and 90% inhibition of SVNT to calculate accuracy. Correlations of anti-RBD to SVNT among all groups were excellent with R= 0.7903, R=0.7843, R=0.8153 among non-comorbid, SLE and CKD groups, respectively, with significantly higher correlation among the PLWH group (R=0.8877; p-value=0.0072) compared to non-comorbid group. The accuracy of the anti-RBD test among PLWH and CKD group was similar with the non-comorbid but showed lower sensitivity in the SLE group (p=0.000014). The specificity of the test remained high in all groups. In conclusion, the Anti-RBD test had excellent correlation to SVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect presence of low neutralization capacity, prompting additional vaccination.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

This study introduces a novel nanocomposite coating composed of PANI/CeO2 nanocomposite films, aimed at addressing corrosion protection needs. Analysis through FTIR spectra and XRD patterns confirms the successful formation of the nanocomposite films. Notably, the PANI/CeO2 nanocomposite films exhibit a hydrophilic nature. The bandgap energy of the PANI composite film measures at 3.74 eV, while the introduction of CeO2 NPs into the PANI matrix reduces the bandgap energy to 3.67 eV. Furthermore, the electrical conductivity of the PANI composite film is observed to be 0.40 S.cm-1, with the incorporation of CeO2 NPs leading to an increase in electrical conductivity to 1.07 S.cm-1. To evaluate its efficacy, electrochemical measurements were conducted to assess the corrosion protection performance. Results indicate a high protection efficiency of 92.25% for the PANI/CeO2 nanocomposite film.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored. Experimental approach: In this present study, we employed relatively new bioinformatics approaches, analyses of microarray data, western blot, RT-PCR, and functional assays to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells, and inversely correlates with the aberrant expression of SOD2. Results: This converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced oncogenicity, which is effectively inhibited by 4-AAQB as evidenced by inhibited cell viability and proliferation, as well as, attenuated migration, invasion and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p, akin to short-interfering RNA reduced SOD2 expression, correlates with the concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2, with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in vitro and in vivo. Additionally, 4-AAQB synergistically potentiates FOLFOX anticancer effect by eliciting the re-expression of SOD2-suppressed hsa-miR-324 and inhibiting SOD2-mediated tumorigenicity. Conclusion: Our findings highlight the pre-clinical anti-CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential novel therapeutic strategy for CRC patients.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR>MTYR>>TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

Crown of thorns starfish (Acanthaster planci) are coral predators with advantages of having toxicity in their venom and tissue regeneration capabilities. With all these characteristics, only a handful of studies have highlighted the association of microorganisms with this organism. Crown of thorns starfish are common in Fiji and their analyses of microbial diversity for secondary metabolites could be of great interest to the scientific community. This study is an attempt to investigate Fijian-based A. planci for their venom and associated actinomycetes antibacterial activity and further identify the type of enzymes present in the crude venom extract. The CoTS venom extract (0.192 g) harbor enzymes such as gelatinase, caesinase, and amylase. An abundant and potent actinomycete strain, represented as FJA1 showed antibacterial activity against Enterococcus faecium with an inhibition zone of 10 mm. Moreover, all pathogenic test microorganisms were resistant against concentrations of 500 µg and 1 mg of A. planci venom extract.

Coffee is rich in caffeine (CF), chlorogenic acid (CGA) and phenolics. Differing types of coffee beverages and brewing procedures may result in differences in total phenolic contents (TPC) and biological activities. Inflammation and increases of platelet activation and aggregation can lead to thrombosis. We focused on determining the chemical composition, antioxidant activity and inhibitory effects on agonist-induced platelet aggregation and cyclooxygenase (COX) of coffee beverages in relation to their preparation method. We prepared instant coffee and brewed coffee beverages using drip, espresso and boiling techniques. Coffee extracts were assayed for their CF and CGA contents using HPLC, TPC using colourimetry, platelet aggregation with an aggregometer and COX activity using ELISA. The findings have shown all coffee extracts, except the decaffeinated types, contained nearly equal amounts of CF, CGA and TPC. Inhibitory effects of coffee extracts on platelet aggregation differed depending on the activation pathways induced by different agonists. All espresso, drip and boiled coffee extracts caused dose dependent inhibition of platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid (ARA). The most marked inhibition was seen at low doses of collagen or ARA. Espresso and drip extracts inhibited collagen-induced platelet aggregation more than purified caffeine or CGA. Espresso, boiled and drip coffee extracts were also a more potent inhibitors of COX-1 and COX-2 than purified caffeine or CGA. We conclude that inhibition of platelet aggregation and COX-1 and COX-2 may contribute to anti-platelet and anti-inflammatory effects of espresso and drip coffee extracts.

Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies has performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations — specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to ATG-G (7.5% vs. 38.3%, p=0.001). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p<0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p=0.008) and a higher median CMV copy number (1000 vs. 0, p=0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p=0.005). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year probability of relapse while comparing ATG-T and ATG-G (32.0% vs 40.3%, p=0.423; 63.9% vs 55.7%, p=0.438, respectively).

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1>49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p<0.05). In addition, patients diagnosed with adenocarcinoma, PDL1<49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p<0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Erosion caused by the repeated impact of particles on a substance surface is a usual wear method resulting in gradual and continual loss of objects. It is a crucial problem in several modern industries because their surfaces are frequently subjected to destructive erosive situations. Polymers and their hybrid materials include several applications to be used as a coating in the form of powder for different applications. This review paper aims to provide extensive information on the erosion behavior of thermoset and thermoplastic neat resin and their hybrid materials composites. Focus is specifically paid to highlight the influence of properties of selected materials, impingnation parameters such as incident Angle of erodent, impact velocity of erodent, erodent nature, and the erosion mechanism. The review further extends the information about the erosion techniques and numerical simulation methods used for wear studies of surfaces. An investigation has been carried out for researchers to explore the selection of materials and methods in terms of conditions and parameters to meet the current and future needs and challenges for the protection of surfaces of the advanced industries. During review according to the findings achieved from the literature of the past fifty years, it has been noted that the thermoplastic nature of the composite is a key component to determine the anti-wear properties, the composites with lower glass transition, higher ductility, and greater crystallinity can provide better protection to erosion in advance surface applications.

Three new polyketides (penidihydrocitrinins A–C, 1–3) and 14 known compounds (4–17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1–17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on microglial activation in LPS-stimulated BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Moreover, compounds 6, 7, and 8 not only suppressed osteoclastogenesis, but also promoted osteoblast mineralization.

Vaginal ecosystem is a unique environment where, in physiological conditions, lactobacilli dominate. However, also pathogenic microbial species, responsible of vaginitis and vaginosis, can harbor vaginal microbiota. To extend the data published by De Seta and Larsen in Pathogens (2021), here we analyzed both the anti-Candida and anti-inflammatory properties of the vaginal gel formulation, Respecta® Balance Gel (RBG), commercialized as an adjuvant to treat vaginitis and vaginosis. We evaluated its activity by an in vitro model where a monolayer of A-431 vaginal epithelial cells was infected by Candida albicans in the presence of RBG or the placebo formulation (pRBG). Specifically, we tested the RBG capacity to counteract C. albicans virulence factors as well as their anti-inflammatory properties. Our results show that, unlike the placebo, RBG reduces ,reduces, C. albicans adhesion, its capacity to form hyphae and C. albicans-induced vaginal cell damage. Interestingly, both RBG and pRBG reduce LPS-induced IL-8 secretion (being RBG the most effective) demonstrating that also the placebo retains anti-inflammatory properties. By our experimental approach we highlight the possible role of farnesol on such effects, but we would like to point out that lactic acid, polydextrose and glycogen too must be relevant in the actual application. Taken together, our results show that RBG impairs C. albicans virulence and is able to reduce the inflammation in the vaginal environment, ultimately allowing the establishment of a balanced vaginal ecosystem.

Abstract: A punicalagin is a metabolic product of pomegranate fruits and peeled. We have compiled the recent literature review from different sources. The extract of pomegranate fruits and peel has been reported for health-beneficial properties in inflammation-associated chronic disease and the regulatory role in NF-KB, MAPK, IL-6/JAK/STAT3, and PI3K/AKT/mTOR signaling pathway. Punicalagin is an ellagitannin found in the peel of pomegranate (Punica granatum). It is a polyphenol with proven biological/pharmacological activities like antioxidant, hepatoprotective, an-ti-atherosclerotic, anti-cancer, anti-neurological, anti-diabetic, and anti-digestive. The extracts have a rich source of hydrolyzable tannin and anthocyanin exhibiting strong anti-neoplastic properties. Anti-cancer activities of pomegranate with reference to modulated signaling pathways in various cancer diseases have been recently reported. The punicalagin-induced redirection of the signal-transduction pathway from survival and proliferation into the cell cycle by arrested the living cells. Apoptosis senescence and autophagy and thus compromising neoplastic progression are delineated. This review is based mainly on data obtained from various sources including the in-vitro cell line model and its activities that are concerned with the effect of punicalagin activities on various cell types.

Although conventional chemotherapeutic drugs are the first line of treatment for cancer, they have numerous side effects. One of the emerging challenges in cancer treatment is drug resistance. Nat-ural compounds have proven effective against various hallmarks of cancer for their multi-target inhibition properties, but especially for their ability to synergistically bypass low bioavailability. Methods: The present study investigated the in vivo antitumor effects of a combination of two natural dietary agents, epigallocatechin-3-gallate (EGCG) from Camelia Sinensis and curcumin, a component of turmeric (Curcuma longa). We aimed to compare, for the first time in vivo, the antiangiogenic and antitumor effects of sunitinib with the combination of curcumin and EGCG in a mouse model of renal cell carcinoma (ccRCC). It was shown that they are able to inhibit cell survival, proliferation of several type of cancer, including renal cell carcinoma (ccRCC), by mod-ulating different signaling pathways and that their combination respect to single compound syn-ergistically decreased angiogenesis. Results: Herein, we highlighted that these compounds inhib-ited the growth of xenografted renal cancer in nude mice by significant inhibition of tumor vol-ume, tumor weight and CD31 expression with no signs of hepatic toxicity. Moreover, mice treated with these natural compounds showed a significant reduction in angiogenesis and an improve-ment in survival rate with p<0.05. Finally, pretreatment of mice with a diet containing 0.6% curcumin before injection of tumor cells showed a significant inhibition of tumor engraftment in 60% of mice with respect to controls and other groups. Conclusions: Taken together, our data in-dicate, for the first time, that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC and with less toxicity than sunitinib and provide an important rationale for future clinical development for chemoprevention and treatment of re-nal cancer.

The goal of this study was to develop a rapid diagnostic kit for rheumatic disease and systemic lupus erythematosus (SLE) screening. A novel rapid vertical flow assay (VFA) was engineered and used to assay anti-nuclear (ANA) and anti-dsDNA (αDNA) autoantibodies from systemic lupus erythematosus (SLE) patients and healthy controls (HC). Observer scores and absolute signal intensities from the VFA were validated by ELISA. The rapid ten minute point of care VFA test engineered demonstrated a limit of detection of 0.5 IU/ml for ANA and αDNA autoantibodies in human plasma with inter-operator CV of 19% for ANA and 12% for αDNA. Storage stability was verified over a three-month period. When testing anti-dsDNA and ANA levels in 22 SLE and 18 HC serum samples, the duplex VFA revealed 95% sensitivity, 72% specificity and 84% accuracy in discriminating disease groups, comparable to the gold standard, ELISA. The rapid αDNA/ANA duplex VFA can potentially be used in primary care clinics for evaluating patients or at-risk subjects for rheumatic diseases and for planning follow-up testing. Given its low cost, ease and rapid turnaround, it can also be used to assess SLE prevalence estimates.

: Given that cancer is a disease that is rampant in the world and especially in Africa where the population has enormous difficulty in treating it, plants are a safer and less expensive alterna-tive. Cassava is one of the plant species valued in Benin because of its numerous medicinal and nutritional virtues. This study evaluated the biological activities of amygdalin from the organs of three cassava varieties most produced in Benin (BEN, RB, and MJ). HPLC analysis was used to quantify amygdalin in cassava organs and derivatives. Phytochemical screening was performed to determine secondary metabolite groups. DPPH and FRAP methods were used to assess anti-oxidant activity. Cytotoxicity of the extracts was tested on Artemia salina larvae. The an-ti-inflammatory activity was evaluated in vivo on albino mouse paw edema model induced by 5% formalin. The anticancer activity was evaluated in vivo on Wistar rats rendered cancerous by 1,2-dimethylhydrazine (DMH) using 5-fluorouracil as reference molecule. The results showed that the organs of all three-cassava varieties contained glycosides, flavonoids, saponosides, ster-oids, tannins, coumarins, and cyanogenic derivatives. Young stems and fresh leaves of cassava had the highest amygdalin concentration with 11142.99 µg 10 g-1 and 9251.14 µg 10 g-1 respec-tively. The Agbeli derivative was more concentrated in amygdalin with a content of 401.56 µg 10 g-1 than the others derivatives. The antioxidant activity results showed that the amygdalin ex-tracts were found to be DPPH radical scavengers with IC50 values ranging from 0.18 mg mL-1 to 2.35 mg mL-1. The cytotoxicity test showed no toxicity of the extracts toward shrimp larvae. Ad-ministration of amygdalin extracts from the leaves of BEN and MJ varieties prevents inflamma-tory edema. The percentages of edema inhibition varied between 21.77% and 27.89%. These val-ues are similar (p> 0.05) to that of acetylsalicylic acid (25.20%). Amygdalin extract of BEN variety significantly (p<0.0001) reduces edema. Cancer induction with DMH was inhibited by both BEN extract. In both preventive and curative treatments, rats fed with amygdalin extracts showed low anti-cancer activity under the effect of DMH and the significant difference in biochemical results. Thus, the organs of all three cassava varieties studied have secondary metabolites and good an-tioxydant activity. The leaves contain high levels of amygdalin and can be used as an-ti-inflammatory and anticancer agents.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, the imperative of employing natural antioxidants becomes apparent. In this study, we delve into the antioxidant and hepato-protective properties of Pistacia lentiscus against 7,12-dimethylbenz(a)anthracene-induced toxicity, alongside exploring its potential anticancer attributes. Our investigations unveil Pistacia lentiscus's anti-proliferative efficacy against human breast cancer cell lines. Notably, 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed-group compared to controls (p&lt;0.05). Nonetheless, Pistacia lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces Pistacia lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Our findings underscore Pistacia lentiscus's robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene-induced mammary cancer initiation. We posit that Pistacia lentiscus may serve as a prophylactic agent against breast cancer instigated by this carcinogen.

The influence of the addition of 2.5, 5, 7.5, and 10.0% of dried Enoki and Maitake mushrooms on the content of bioactive compounds and some pro-health properties of pasta was studied. The qualitative and quantitative analysis of phenolic compounds performed using the LC-MS/MS technique indicated the highest amount of phenolic compounds in pasta supplemented with Maitake. However, all pasta enriched with Enoki mushrooms contained statistically significant-ly higher content of α-glucans in comparison to the control. In samples subjected to gastrointes-tinal digestion, the antioxidant, and potential anti-inflammatory activities were significantly higher than ethanolic and PBS extracts of samples. The ethanolic extracts from pasta fortified with dried Enoki and Maitake mushrooms had higher antioxidant activity (in some of the anti-radical and reducing power assays ) as well as a higher ability to inhibit lipoxygenase (E2.5 and E5 samples) compared to the control sample. Also some in vitro digested samples of pasta en-riched with dried Enoki and Maitake mushrooms showed higher chelating power (E10, M7.5 and M10); reducing power (E5, E7.5, and M10) and lipoxygenase inhibition (E7.5, E10 and M10) than the control. In conclusion, Enoki and Maitake mushrooms can be used for fortification of semo-lina pasta, conferring healthier characteristics of the product.

In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

Abstract: This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and anti-microbial properties. Sinigrin and glucoraphanin are converted by the β-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In-vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant "priority pathogens" and also act as anti- cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.

Cancer being a multi-factorial disease, a multi-target approach is needed to treat it with minimal side-effects. Therefore, combined use of a proven herbal formula with chemo-therapy could be the better therapeutic. It may maintain homeostasis by synergistically targeting multiple signaling pathways involved in tumorigenesis, thus circumventing recurrence, resistance, and immunosuppression. Here we aim to determine the effectiveness and safety of an FDA-approved herbal formula, SR033 in combination with 5-fluorouracil (5FU) and paclitaxel (PTX). We report chemo-sensitization and chemo-synergy in HeLa and MCF-7 cell lines, immunomodulation of COX-2, PD-L1, VEGF and TGFβ and overall survival in-vitro and in-vivo via oral and topical delivery of SR033. In-vitro, SR033/5FU significantly reverses 5FU and PTX-resistance, lower COX-2, and PD-L1, resulting in TGFβ/ VEGF axis modulation. Furthermore, the study suggests that due to anti-oxidative potential of SR033, oral administration exerts chemo-preventive activity and restores cellular compartment in solid tumor and ascites-bearing mice models. Furthermore, the topical application, SR033L with low-dose 5FU increases survival rate, reduces tumor growth, and completely restores local and peripheral neutrophil-lymphocyte ratio in solid tumor mice model. The study indicates that SR033 could be a strong candidate in combination with low-dose 5FU and PTX for a holistic approach to cancer management.

Kummerowia striata is a traditional medicine used for the therapy of inflammation-related diseases. Herein, we investigated the anti-melanogenic and antioxidant activities of an ethanolic extract of K. striata (EKS) using a number of in vitro and cell culture model systems. The anti-melanogenic effect was assessed in B16F10 melanoma cells based on melanin synthesis and in vitro tyrosinase inhibitory activity and the anti-oxidant activity assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); EKS exhibited strong anti-oxidant activities in both the assays. The expression of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor was decreased in a dose-dependent manner at mRNA and protein levels upon treatment with EKS. Notably, EKS did not affect the cell viability at all the EKS concentrations used in this study, indicating that EKS-mediated inhibition of melanin synthesis is not accompanied with cytotoxicity. Collectively, our findings demonstrate, for the first time, that EKS possesses anti-melanogenic and anti-oxidant activities, and suggest that further evaluation and development of EKS as a functional supplement or cosmetic might be useful for skin whitening and for reduction wrinkles.

In order to tackle the issue of severe rocking phenomenon under seismic conditions in structures equipped with steel spring isolation bearings, this paper investigates a novel type of anti-rocking bearing. Firstly, the structural configuration and working principle of the novel anti-rocking bearing are introduced, and a design method for bearing parameters is proposed. Secondly, a finite element analysis model is established using SAP2000 software to conduct nonlinear dynamic time history analysis under seismic loading. The analysis results show that the structural arrangement of the novel anti-rocking bearing reduces both the vertical displacement difference and the rocking angle of the isolation layer. The bearing exhibits a certain level of anti-rocking effect, but it may cause significant tensile forces in some bearings, necessitating the installation of anti-tensile reinforcement. The effectiveness of the anti-rocking effect improves as the stiffness of the steel tension rod in the bearing increases; however, it also leads to higher maximum tension in individual bearings as well as the total tension in all bearings. For structures equipped with the novel anti-rocking bearing, the acceleration amplifies under most cases, with amplification coefficients ranging from 0.82 to 1.55. The performance of the novel anti-rocking bearing varies significantly for different seismic waves. The stiffness of the steel tension rod should be determined considering the reference pressure of the bearing and the maximum designed tension of the bearing. Through the finite element simulation of the bearing, the mechanical properties of the bearing are basically the same as the theoretical analysis results. For the cylinder and the joint bearing, certain structural measures need to be taken to ensure its strength and stiffness.

Biological polymers such as tissue-engineered scaffolds and skin grafts with improved properties are very required in the pharmaceutical field. The wound-dressing gelatin/chitosan/moringa leaf extract (G-CH-M biopolymer) was synthesised and characterised. The blood compatibility, anti-inflammatory, antioxidant, and antibacterial activities of the biopolymer were investigated. Our results showed that S. aureus swarming motility was drastically affected. However, the biopolymer had no significant effect on the swarming motility of E. coli compared to the control. In addition, biopolymers showed high antibacterial capacities, especially against S. aureus. The biopolymer was also found to be effective in protecting plasmid DNA against oxidative stress. Furthermore, the biopolymer exhibits greatly suppressed hemolysis (lower than 2%), even at a high concentration of 50 mg/mL. These results indicated that this novel biopolymer formulation could be further developed for wound care and contamination prevention.

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from the patients’ bodies. A potential strategy called “lock-in apoptosis” targeting the budding phase of life cycle of virus leading to susceptibility to apoptosis of HIV-1 infected cells for elimination of HIV-1 reservoirs and ultimately for a complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA) approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC₉₀ value of 1.5 μM.

Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

(1) Background: Colon cancer is one of the leading causes of cancer morbidity and mortality globally. It is a multi-step process that involves genetic and epigenetic modifications leading to histological and morphological changes. Several complementary therapeutic options have been analyzed, shedding light on plant-based medication as a potential treatment for colon cancer. Flavonoids such as quercetin are known to have anti-cancer and anti-inflammatory properties. This in vitro study examines quercetin's anti-inflammatory, anti-apoptotic, anti-angiogenesis effects and antioxidant properties in colon cancer cells. (2) Methods: The antioxidant capacity of quercetin-treated cells was investigated using biochemical assays, and angiogenesis and cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA). The epigenetic modulation and differential expression of aging, apoptotic, and proliferation genes, and Histone deacetylases (HDACs) were also investigated. (3) Results: In this study, the quercetin-treated group significantly reduced the antioxidant enzymes, cytokines, and VEGF levels, altering the expression of epigenetic factors. Quercetin also induced significant senescence in colon cancer cells. Moreover, a considerable increase was observed in the apoptotic and hTERT genes. In contrast, a decrease in p53, proliferation genes, and HDACs was observed, providing a basis for the clinical use of quercetin in cancer treatment. (4) Conclusion: In vitro studies showed that quercetin treatment efficiently induces senescence and apoptosis in colon cancer cells. We also found that quercetin effectively modulated the expression of p53, Wnt1, CTNNB1, and HDACs, indicating that it could be used to treat colon cancer.

Dendrobium okinawense is an endangered epiphytic orchid, and there has been no scientific report so far on its propagation. Protocorm is mass of cell, and protocorm-like bodies (PLBs) look alike protocorm produced by vegetative explants in vitro. Regeneration of PLBs is the most efficient technique for the orchids micro-propagation. We used different light emitting diodes (LEDs) for the efficient PLB organogenesis of D. okinawense. PLBs regenartion under green and red LED surpassed respectively 81.1% and 71.6% in numbers, and respectively 80.8% and 57.8% in fresh weight over white fluorescent light. We manipulated the culture media by different concentrations of PCIB and HMI. PLBs organogenesis promoted by low concentration, it increased respectively 35.9% and 19.3% over control by 0.01 mg/L PCIB and 0.01 ml/L HMI in numbers. Green LED and PCIB independently produced mostly similar numbers of new PLBs. Interestingly, culture media with 0.01 mg/L of PCIB further increased 8.5% of the numbers of PLBs under green LED, whereas the culture media with 0.01 mg/L HMI reduced the number of PLBs under green LED. PLBs culture under green LED with very low concentrations of PCIB manipulated culture media can significantly increase their organogenesis of D. okinawense.

Background: Pteropodine (PT) is a component of some plants with potentially useful pharmaco-logical activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the an-ti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. Methods: To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect was evaluated by determining the myeloperoxidase enzyme activity. Results: PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 52 to 74% of inhibitory effect of PT in the rat paw edema test, 52% of reduction of the pleural exudate volume, and low neutrophil count (28%), when compared to the control group. We also found a 81% of inflammatory inhibition of the ear edema, and a significant myeloperoxidase enzyme inhibition by the three doses of PT. Conclusions: PT exerted a potent an-ti-inflammatory effect in the acute inflammation model in rodents.

In the present paper, we introduce the phytoscreening and antiradical characteristics of conker extracts prepared from 2-, 1-year stored and just collected plants as well as the anti-inflammatory effect of oinment composition based on the extract.

Epilepsy is a chronic neuronal disorder characterized by periodic, unpredictable, and recurrent seizures due to either a genetically determined or an acquired brain disorder. Although many anti-epileptics drugs (AEDs) are developed to control epilepsy, 30% of patients still need additional drugs or experience recurrent seizures and psychiatric and behavioral side effects. Thus, the need for medical care for patients with uncontrolled epilepsy remains unmet. The Genus Artemisia L. is one of the largest genera in the Asteraceae family with more than 500 species widely distributed in Europe, Asia, and North America. Many Artemisia species have been used in various treatments since ancient times as folk remedies. They demonstrated strong antioxidant, anti-inflammatory, antimicrobial, antimalarial, and antitumor activity. Recent studies reveal that some species of Artemisia demonstrated a therapeutic benefit for epilepsy by its anti-oxidant, anti-inflammatory, neuroprotective, and anticonvulsant properties. In this review, we investigate the current state of the literature regarding the neuroprotective and antiepileptic potentials of the genus Artemisia and its possible underlying mechanisms.

Fracking in the UK has yet to reach full industrial development but it is still subject to significant opposition. This study uses Beck’s Risk Society theory and anti-politics to examine the views voiced by opponents to fracking in Yorkshire, England. A qualitative approach was used; local newspaper reports were evaluated alongside semi-structured interviews with protesters to provide a thematic analysis. Although there are signs of post-materialist concerns with the environment these issues did not dominate the discussion. Scientists were not held responsible for the risks involved in fracking. Instead economic greediness of politicians and austerity measures were perceived as putting the environment and people’s health at risk. Interviewees thought fossil fuel energy production was economically advantaged over more sustainable energy and jobs in the low carbon economy. Protesters’ trust in politicians had been eroded but faith in democracy remained. It is suggested a citizen-led deliberative approach to all the concerns raised, not simply those relating to scientific risk, might achieve some level of resolution over fracking in the UK.

Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, Oleanolic Acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, twenty new Oleanolic acid derivatives had been designed and synthesized.A549 and SGC-7901 cells were used to screen the antitumor activity in vitro through the standard MTT method. The compounds, II₃, III₅ and Ⅳ_4, exhibited more potent cytotoxicity than positive drugs.

Influenza viruses cause acute respiratory infections responsible for significant mortality and morbidity around the world. Various factors, such as antigenic drift, allow influenza strains to avoid being fully suppressed by seasonal vaccines. This has led to the increased scrutiny of antivirals as treatment and prophylaxis options for seasonal outbreaks and potential pandemics. Unfortunately, many influenza antivirals suffer from a lack of adequate clinical trials, as well as a lack of toxicity data. This is especially true of umifenovir (arbidol), a drug popularly used for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, though widely prescribed, display a potential for future resistance. Adamantanes, while proven to be effective in treating influenza A, are already encountering rapid and widespread cross-resistance and are effectively obsolete. Baloxavir marboxil, a newer antiviral, shows promise in treating acute uncomplicated influenza and may avoid the development of resistance when co-administered with other antiviral drugs. Indeed, the low genetic barrier to resistance associated with influenza antivirals could potentially be overcome by co-administration with other antivirals. This review explores the most widely prescribed antivirals for influenza treatment, their mechanisms of action, and the data currently available about their susceptibility to resistance and efficacy.

Antimicrobial peptides provide a powerful toolkit for combating multidrug resistance. Combatting eukaryotic pathogens is complicated by the fact, the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria, (symbionts of entomopathogenic nematode species), release a series of non-ribosomal templated antimicrobial peptides, some may be potential drug candidates. The ability of an entomopathogenic nematode /entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product, explaining that those gene complexes which are responsible for the biosynthesis of different non-ribosomal templated antimicrobial protective peptides (including those which are potently capable to inactivate the protist mammalian -pathogen Leishmania and the gallinaceous bird pathogen Histomonas) are co-regulated. Our approach is based on comparative antimicrobial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated antimicrobial peptides, that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourages us to forecast that the recently discovered “easy-PACId” research strategy is suitable for constructing EPB strains producing and releasing single, harmless, non-ribosomal templated antimicrobial peptides with considerable drug, (probiotic) -candidate potential.

Objective: The hypoglycemic, hepatorenalprotective, and antioxidant Activities of Cyperus rotundus rhizomes extract in an alloxan-induced diabetic rat model were investigated in this work.Methods: 25 Male rats were divided into 5 groups: normal control, diabetic control, diabetic of C. rotundus (200 mg/kg b.w), diabetic of C. rotundus (400 mg/kg b.w), diabetic of glibenclamide (0.6mg/kg).Treatments were administered orally for 6 weeks.Results: A single injection of alloxan to rats (150mg/kg b.w) caused pathological alterations in all studied parameters and histological structure of the pancreas. On the other hand, results showed that oral administration of C. rotundus rhizomes extract in dose of 200 and 400 mg/kg caused significant reduction in glucose, HbA1C%, α-amylase level and plasma lactate together with significant elevation in serum insulin, serum pyruvate with an improvement in insulin resistance. In line with amelioration of the diabetic state, C. rotundus rhizomes extract improved of the liver and kidney functions, and oxidative marker levels. Moreover, the extract succeeded to reduce the elevated serum total cholesterol, triglyceride (TG) and low-density lipoprotein- cholesterol (LDL-C) levels and to elevate the reduced high-density lipoprotein- cholesterol (HDL-C) level of diabetic rats.Conclusion: The investigation data concluded that C. rotundus rhizomes extract could be used as alternative treatments as antidiabetic, antioxidant and antihyperlipidemic, and agent as well as in liver and kidney protective in alloxan induced-diabetic rats. This may be related to the presence of saponin glycosides, polyphenols, flavonoids, and terpenoids in the ethanolic extract of C. rotundus rhizomes, which was discovered by phytochemical screening in this study to be present in the plant.

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

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

This study explores the development of an oil-in-water (O/W) emulsion with a high concentration of ostrich oil, rich in omega-3, -6, and -9 fatty acids, for potential skincare applications. Utilizing Span and Tween emulsifiers, an optimized O/W emulsion containing 20% w/w ostrich oil and 15% w/w mixed emulsifiers was formulated through homogenization, demonstrating the smallest droplet size (5.01 ± 0.43 μm) and appropriate zeta potential (-32.22 mV). The emulsion exhibited antioxidant and antibacterial properties against Staphylococcus aureus, suggesting its suitability for skincare. Stability tests over 6 months at varying temperatures (4 °C, 25 °C, 45 °C) confirmed the emulsion's physical and microbial stability, emphasizing its potential for topical applications. Despite slight changes in acid values (AV) and peroxide values (PV), results remained within acceptable limits. Cytotoxicity assessments on human dermal fibroblasts indicated the emulsion's safety, supporting its suitability for skin application. The emulsion demonstrated antibacterial efficacy against S. aureus and enhanced antioxidant activity compared to ostrich oil alone. The study underscores the importance of emulsification in optimizing the efficacy and stability of ostrich oil in skincare formulations, offering valuable insights for practical applications where stability is critical.

N-palmitoylethanolamine (PEA) is an endocannabinoid-like compound first encountered within lipid fractions of specific foods and has intrigued researchers since the 1950s due to its therapeutic effects. This study aims to explore the therapeutic promise held by PEA as an anti-inflammatory and immunomodulatory agent. Therapeutic impact of PEA reverberates across diverse physiological systems, as the central nervous system, gastrointestinal tract, vascular network, digestive and respiratory system. Additionally, it was effective in pain management, reduction of inflammation and immune responses. These attributes have fostered collaborations targeting conditions such as Alzheimer's disease, multiple sclerosis, cerebral ischemia, neuroinflammation, general inflammation, pain, coagulopathy, steatohepatitis, and acute lung injury. PEA operates both independently and in synergy with other compounds, like paracetamol, luteolin, and oxymetazoline. This efficacy stems from its interactions with pivotal targets including PPARα, PPAR-δ, PPAR-γ, CB1, CB2, GPR55, and TRPV1. Additionally, PEA exerts a direct influence on the inflammatory cascade, orchestrating precise adjustments in immune responses. Numerous animal studies have elucidated the inherent potential of PEA. Nevertheless, the imperative of reinforcing clinical investigation is evident. This review notably underscores the pivotal necessity for methodologically rigorous clinical trials to definitively establish the translational efficacy of PEA in ameliorating diverse inflammatory pathologies within the human milieu.

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

Cardiovascular disease is the most common cause of death. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases, so anti-inflammatory and antioxidant agents that modulate redox balance have become the targets of research to evaluate their molecular mechanisms and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant effects due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also stands out for its anti-inflammatory activity, possibly interrelated with its antioxidant effect, as well as for its modulation of lipid and glucose metabolism. Considering the potential positive effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, this paper describes the molecular and cellular mechanisms related to the antioxidant and anti-inflammatory properties of this carotenoid in cardiovascular diseases, especially atherosclerosis.

Background: Enterovirus infections affect people around the world, causing a range of illnesses, from mild fevers to severe, potentially fatal conditions. There are no approved vaccines or treatments for enterovirus infections. Methods: We have tested our library of broad-spectrum antiviral agents (BSAs) against echovirus 1 (EV1) in human adenocarcinoma alveolar basal epithelial A549 cells. We also tested combinations of the most active compounds against EV1 in A549 and human immortalized retinal pigment epithelium RPE cells. Results: We confirmed anti-enteroviral activities of pleconaril, rupintrivir, cycloheximide, vemurafenib, remdesivir, emetine, and anisomycin and identified novel synergistic rupintrivir-vemurafenib, vemurafenib-pleconaril and rupintrivir-pleconaril combinations against EV1 infection. Conclusions: Because rupintrivir, vemurafenib, and pleconaril require lower concentrations to inhibit enterovirus replication in vitro when combined, their combinations may have fewer side effects in vivo and therefore should be further studied in pre- and clinical trials.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: Section one addresses the relationship between the anti-inflammatory bioactivities of different phospholipids in relation to their structures and compositions. Sections two and three are dedicated to the structures, functions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option due to its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed.

Many neurodegenerative diseases are directly related to the formation of toxic protein aggregates, such as Parkinson’s and Alzheimer’s diseases, which are associated with the aggregation of alpha-synuclein (α-syn) and beta-amyloid (Aβ ), respectively. In this context, protein fibrils are the hallmark of these neurodegenerative diseases. In this sense, planning or designing compounds that are capable of preventing or reducing the formation of protein aggregation in the brain can be of fundamental importance for the curative treatment of these diseases. This work presents an in silico and experimental study to investigate the inhibitory potential of the ligands Octovespin (bioinspired by the wasp venom Polybia Occidentalis) and Fraternine-10 (bioinspired by the wasp venom Parachartergus fraternus wasp) against the aggregation of fibrils of the peptides Aβ(17-42) and α-syn, respectively. Using molecular docking and molecular dynamics simulations with 100 ns, the disaggregation capacity of these ligands was studied. The results obtained indicate that Octovespin and Fraternine-10 interact with the Aβ and α-syn protein fibrils throughout the simulation time. The RMSD values and the interactions with amino acids responsible for fibril aggregation demonstrate that both Octovespin and Fraternine-10 have a significant disaggregation potential, which corroborates the observations in vitro and in vivo. Furthermore, experimental results of Fraternine-10 demonstrate an anti-aggregation effect, indicating that it can promote the disaggregation of fibrils and prevent them from aggregating again to form oligomers. These discoveries qualify these molecules as potential candidates to become medicines against Parkinson’s and Alzheimer’s diseases.

Leptospira, which are known to be important disease-causing agents transmitted between animals and humans, results in significant illness and, in some cases, significant death in human populations. This study aims to examine the genomic structure of Leptospira interrogans serovar Copenhageni strain FDAARGOS_203 to identify the specific genetic factors that contribute to antimicrobial resistance (AMR) and defense against phages. The genome, consisting of two contigs totaling 4,630,574 base pairs, underwent thorough examination for protein-coding sequences, transfer RNA genes, and ribosomal RNA genes. A total of twenty-two antibiotic resistance genes that specifically target essential cellular processes such as cell wall synthesis, DNA replication, and protein synthesis have been identified. Significant among these were gidB, GdpD, and PgsA, each involved in separate aspects of antibiotic resistance. In addition, the investigation explored the defense mechanisms of bacteriophages, revealing the presence of defense islands that contain a range of anti-phage systems, including RM_Type_IV, PrrC, Borvo, CAS_Class1-Subtype-IC, and CAS_Class1-Subtype-IB. This comprehensive genomic analysis enhances our understanding of the molecular mechanisms that determine Leptospira's ability to adapt to various environments. The identified genetic factors linked to AMR and defense against phages not only enhance our scientific comprehension but also provide a basis for focused interventions to reduce the impact of leptospirosis.

Helicobacter pylori infections are still an urgent and hot topic. This is related to the involvement of H. pylori in human diseases (including gastric diseases, gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and diabetes), the number of which is constantly increasing. At the same time, agents effective against these bacteria are decreasing due to spreading resistance. Our research focused on extracts of the Rubus genus, commonly present in Central and Eastern Europe and very useful in folk medicine. Results have shown that the extract from Rubus idaeus 'Willamette' shoots, and the extract from R. idaeus 'Poranna Rosa' fruits and R. idaeus 'Laszka' R. occidentalis Litacz' fruits prevent the formation of biofilm by H. pylori on intravenous infusions (they reduce living cells, which was detected using triphenyl tetrazolium chloride (TTC) as a dye) at concentrations of 6.65 and 16.65 mg/mL, respectively. However, the living bacteria in the formed biofilm are affected by the extract from the shoots of R. idaeus 'Willamette' and the fruit of R. idaeus 'Poranna Rosa' at a concentration of 16.65 mg/ml, and the remaining extracts at a concentration of 33.3 mg/ml. The results of the study of interactions of extracts from Rubus sp. and the 2 antibiotics against H. pylori planktonic bacteria showed doxycycline synergism with all tested extracts, but only the extract of R. occidentalis 'Litacz' with levofloxacin. The remaining tested extracts showed indifference with levofloxacin. However, studies on the interaction between antibiotics and extracts of R. idaeus 'Willamette' shoot showed synergy with doxycycline and levofloxacin, additivity with amoxicillin and clarithromycin, and indifference with metronidazole. The tests were carried out on fragments of intravenous infusions with TTC as a dye. The tested extracts may be elements of broadly understood anti-H. pylori therapy.

Lung cancer accounts for the majority of cancer cases. In recent years, checkpoint inhibitor immunotherapy (ICI) has emerged as a new treatment. A better understanding of the tumor microenvironment, or TMJ, or the immune system surrounding the tumor is needed. Cytokines are small proteins that carry messages between cells and are known to play an important role in the body's response to inflammation and infection. Cytokines are important for immunity in lung cancer. It promotes tumor growth (oncogenic cytokines) or inhibits tumor growth (anti-tumor cytokines) by controlling signaling pathways for growth, proliferation, metastasis, and apoptosis. The immune system relies heavily on cytokines. They can also be produced in the laboratory for therapeutic use. Cytokine therapy helps the immune system stop the growth or kill cancer cells. Interleukins and interferons are two types of cytokines used to treat cancer. This article begins by addressing the role of the tumor microenvironment (TMJ) and its components in lung cancer. This review also highlights the functions of various cytokines such as IL, TGF and TNF.

Cherries have been largely investigated due to their high content in phenolics in order to fully ex-plore their health-promoting properties. Therefore, this work aimed to assess, for the first time, the anti-inflammatory potential of phenolic-targeted fractions of Saco cherry, using RAW 264.7 mac-rophages stimulated with lipopolysaccharide. Additionally, the cytotoxic effects on gastric ade-nocarcinoma (AGS), neuroblastoma (SH-SY5Y) and normal human dermal fibroblast (NHDF) cells were evaluated, as well as the ability to protect these cellular models against induced oxidative stress. The obtained data revealed that cherry fractions can interfere with cellular nitric oxide (NO) levels by capturing NO radicals and decreasing inducible nitric oxide synthase and cyclooxygen-ase-2 expression. Furthermore, it was observed that all cherry fractions exhibited dose-dependent cytotoxicity against AGS cells, presenting cytotoxic selectivity for these cancer cells when compared to SH-SY5Y and NHDF cells. Regarding their capacity to protect cancer cells against oxidative injury, in most assays, the total cherry extract was the most effective. Overall, this study reinforces the sweet cherries incorporation in new pharmaceutical products, smart foods and nutraceuticals.

Polysaccharides from marine algae exhibit beneficial biological activities. In this study, we examined the effect of polysaccharides from Codium fragile (PCF) on prebiotic and anti-obesity activity. PCF increases the growth of specific beneficial microbial populations with concomitant decrease in pathogenic microbes. Further, total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity (DPPH activity) after fermentation with PCF as carbon source were higher than for the glucose as control. Moreover, PCF inhibited adipocyte differentiation by inducing differentiation-related factors when the induction of 3T3-L1 preadipocytes into adipocytes was induced. Therefore, we suggest that PCF can be used as prebiotic material with anti-obesity for human health.

Acquired Immunodeficiency Syndrome (AIDS) which is chiefly originated by a retrovirus named Human Immunodeficiency Virus (HIV), has influenced about 70 million populations worldwide. Even though several advancements have been invented in the field of antiretroviral combination therapy, still HIV has become the dominant reason for death in South Africa, for example. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. In the present day, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate the drugs obtained from natural plants as well as the synthetic derivatives that have been derived from the natural compounds by various chemical reactions. Several plants such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity showing more potent anti-HIV activity along with their structures, SARs & important key findings.

Previously the nanoparticles were synthesized by chemical methods which were costly and toxic to bio-systems. Plant extracts provides simpler, eco-friendly and cost efficient method for synthesizing nanoparticles. Lemon peel extract (LPE) was used to synthesize silver nanoparticles (AgNPs) which were evaluated for their antimicrobial effects after optimizing the pH of extract and concentration of both extract and synthesized AgNPs. The characterization of synthesized AgNPs was carried out using Ultraviolet-Visible (UV-Vis) Spectrophotometer, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Well diffusion method was used to determine the antimicrobial activities of synthesized AgNPs. The presence of phenols and proteins was assumed to reduce the Ag⁺ ion into silver nanoparticles. The characteristic surface plasmon resonance frequency was observed at 405–425 nm for all varying condition of silver nanoparticles synthesis. Furthermore, results revealed that the synthesized AgNPs remains stable upto 75 days. The average particle size was 2–5 nm, calculated with the help of scherrer’s equation by using XRD data. LPE mediated AgNPs (200 µg/mL) showed significant antimicrobial activity, compared to commercially available nanoparticles while LPE (50 mg/ml) showed no effect. LPE mediated AgNPs might get attention of pharmacists in order to design medicines against different diseases including the infections of bacteria.

Ginkgolic acids (GA) have been reported to exhibit anticancer properties, however, the mechanisms remain unclear. This study aims to investigate the mechanisms of GA C13:0 that was isolated from Ginkgo biloba exocarp (GBE) for anti-proliferation, pro-apoptosis and anti-migration effects in human MCF-7 and mouse 4T-1 breast cancer cells. The cytotoxic effect, apoptosis induction and migration inhibition were measured using MTT, TUNEL and Wound healing assays. The expression of mRNA and protein were determined using qPCR and Western blot. Our results showed that no cytotoxicity was found at concentrations of C13:0 below 100µM. The effects of GA C13:0 was further demonstrated by up-regulation of the Bax/Bcl-2 apoptosis pathway and the expression of Apaf-1 protein in the mitochondria. In addition, GA C13:0 also suppressed cell migration and epithelial to mesenchymal transition (EMT) with the increase of E-cadherin expression accompanied by the decrease of Snail, MMP-2, MMP-9 and Vimentin expression. Moreover, GA C13:0 induced cytochrome P450 (CYP) 1B1 expression in aryl hydrocarbon receptor (AhR) pathway. Notably, the up-regulation of CYP1B1 also might play a pivotal regulatory role in mitochondrial and EMT pathways in MCF-7 and 4T-1 cells. Our results may have implications for the development of anticancer agents containing GA as functional additives.

Flaxseed has been recognized as a valuable source of nutrients and bioactive compounds, including proteins that possess various health benefits. In recent years, studies have shown that flaxseed proteins, including albumins, globulins, glutelin, and prolamins, possess anti-cancer properties. These properties are attributed to their ability to inhibit cancer cell proliferation, induce apoptosis, and interfere with cancer cell signaling pathways, ultimately leading to the inhibition of metastasis. Moreover, flaxseed proteins have been reported to modulate cancer cell mechanobiology, leading to changes in cell behavior and reduced cancer cell migration and invasion. This review provides an overview of the anti-cancer properties of flaxseed proteins, with a focus on their potential use in cancer treatment. Additionally, it highlights the need for further research to fully establish the potential of flaxseed proteins in cancer therapy.

Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB), a disease that alt-hough preventable and curable, remains a global epidemic due to the emergence of resistance and a latent form responsible for a long period of treatment. Drug discovery in TB is a challenging task due to the heterogeneity of the disease, the emergence of resistance and an uncomplete knowledge of the pathophysiology of the disease. The limited permeability of the cell wall and the presence of multiple efflux pumps remain a major barrier to achieve effective intracellular drug accumulation. While the complete genome sequence of Mtb has been determined and several potential protein targets have been validated, the lack of adequate models for in vitro and in vivo studies is a limit-ing factor in TB drug discovery programs. In current therapeutic regimens, less than 0.5% of bac-terial proteins are targeted being the biosynthesis of the cell wall and the energetic metabolism two of the most important processes exploited for TB chemotherapeutics. This review provides an overview on the current challenges in TB drug discovery and emerging Mtb druggable proteins, and how chemical probes for protein profiling enabled the identification of new targets and bi-omarkers, paving the way to disruptive therapeutic regimens and diagnostic tools.

Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly-progressive T1D (SPIDDM), also known as latent autoimmune diabetes in adults (LADA). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase-like protein IA-2 (IA-2A), and zinc transporter 8 (ZnT8A) are currently employed in the diagnosis, pathological analysis, and prediction of T1D. GADA can also be detected in non-diabetic patients with autoimmune diseases other than T1D and may not necessarily reflect insulitis. Conversely, IA-2A and ZnT8A serve as surrogate markers of pancreatic β-cell destruction. Combinatorial analysis of these four anti-islet autoantibodies demonstrated that 93-96% of acute-onset T1D and SPIDDM cases were diagnosed as immune-mediated T1D, while the majority of fulminant T1D cases were autoantibody-negative. Evaluating the epitopes and immunoglobulin subclasses of anti-islet autoantibodies help distinguish between diabetes-associated and non-diabetes-associated autoantibodies and is valuable for predicting future insulin deficiency in SPIDDM (LADA) patients. Additionally, GADA in T1D patients with autoimmune thyroid disease reveals the polyclonal expansion of autoantibody epitopes and immunoglobulin subclasses. Recent advancements in anti-islet autoantibody assays include nonradioactive fluid-phase assays and the simultaneous determination of multiple biochemically defined autoantibodies. Developing a high-throughput assay for detecting epitope-specific or immunoglobulin isotype-specific autoantibodies will facilitate more accurate diagnosis and prediction of autoimmune disorders.

The ethanol extract (EE) prepared from the leaves of Tibouchina granulosa, and its fraction in ethyl acetate (fEA) were evaluated concerning their capacity to reduce inflammation in different experimental models. fEA was also studied concerning its chemical constituents. EE and fEA were assayed for their anti-inflammatory potential, using formalin-induced licking behaviour and carrageenan-induced inflammation into the subcutaneous air pouch (SAP) models. Reduction in polymorphonuclear cells (PMN) activation was performed in freshly isolated PMN. Chromatographic analysis of fEA was done by HPLC. Hispiduloside was isolated as the main constituent in fEA and its quantity was estimated to be 11.75% in fEA, 3.05% in EE, and 0.2% (w/w) in the plant. EE (30 mg/kg) significantly reduced the second phase of formalin-induced licking. fEA demonstrated a reduction in leukocyte migration into the SAP. EE and fEA drastically reduced cytokines (TNF-α, IL-1β, and IFN-γ), nitric oxide (NO) production, in vitro PMN migration induced by C5a and IL-8, and TNF-α and IL-1β gene expression. Taken together our data indicate that either ethanol extract or its fEA fraction from leaves of T. granulosa present an anti-inflammatory effect contributing to the pharmacological and chemical knowledge of this species and confirming the rationale behind its traditional use.

Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human’s gastrointestinal tract can create immune response against inflammation and also can develop diseases , including cancer. The bacteria of the gastrointestinal tract of human, can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.

The up-and-coming microfluidic technology is the most promising platform for designing anti-cancer drugs and new point-of-care diagnostics. Compared to conventional drug screening methods based on Petri dishes and animal studies, drug delivery in microfluidic systems has many advantages. For instance, these platforms offer high throughput drug screening, require a small amount of samples, provide an in vivo-like microenvironment for cells, and eliminate ethical issues associated with animal studies. Multiple cell cultures in microfluidic chips could better mimic the 3D tumor environment using low reagents consumption. The clinical experiments have shown that combinatorial drug treatments have a better therapeutic effect than monodrug therapy. So many attempts were performed in this field in the last decade. This review highlights the applications of microfluidic chips in anti-cancer drug screening and systematically categorizes these systems as a function of sample size and combination of drug screening. Finally, it provides a perspective on the future of the clinical applications of microfluidic systems for anti-cancer drug development.