Cardioprotective Effects of α-Asarone Against Hexavalent Chromium-Induced Oxidative Damage in Mice.

Introduction: This comprehensive study investigated the therapeutic potential of α-asarone in mitigating myocardial oxidative damage, primarily induced by hexavalent chromium (Cr(VI)) exposure in mice. Methods: In this experiment, 24 mice were divided into four groups to assess the cardioprotective role of α-asarone. The study focused on two treatment groups, receiving 25 mg and 50 mg of α-asarone, respectively. These groups were compared against a control group subjected to Cr(VI) without α-asarone treatment, and a normal control negative group. The key biochemical parameters evaluated included serum levels of Creatine Kinase-MB (CK-MB) and Troponin I, markers indicative of myocardial damage. Additionally, the levels of Malondialdehyde (MDA) were measured to assess lipid peroxidation, alongside the evaluation of key inflammatory biomarkers in cardiac tissue homogenates, such as Tumor Necrosis Factor-α (TNF-α) and Interleukin-1ß (IL-1ß). Results Remarkably, α-asarone treatment resulted in a significant reduction in these markers compared to the control group. The treatment also elevated the activity of cardinal antioxidant enzymes like catalase (CAT) and superoxide dismutase (SOD), and reduced the glutathione (GSH). Furthermore, a notable upregulation of Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) in cardiac tissue homogenates was observed, highlighting a potential pathway through which α-asarone exerts its protective effects. Histopathological analysis of cardiac tissues revealed that α-asarone ameliorated the structural lesions induced by Cr(VI). The study thus provides substantial evidence that α-asarone ameliorates Cr(VI)-induced cardiotoxicity through a multifaceted approach. It enhances cardiac enzyme function, modulates free radical generation, improves antioxidant status, and mitigates histopathological damage in cardiac tissues. Given these findings, α-asarone emerges as a promising agent against Cr(VI)-induced myocardial injury. Purpose: This study paves the way for further research into the cardioprotective properties of α-asarone and its potential application in clinical settings by specifically exploring the protective efficacy of α-asarone against Cr(VI)-induced cardiotoxicity and delineating the underlying biochemical and molecular mechanisms involved.

Harnessing the power of bee venom for therapeutic and regenerative medical applications: an updated review.

Honeybees have been helpful insects since ancient centuries, and this benefit is not limited to being a honey producer only. After the bee stings a person, pain, and swelling occur in this place, due to the effects of bee venom (BV). This is not a poison in the total sense of the word because it has many benefits, and this is due to its composition being rich in proteins, peptides, enzymes, and other types of molecules in low concentrations that show promise in the treatment of numerous diseases and conditions. BV has also demonstrated positive effects against various cancers, antimicrobial activity, and wound healing versus the human immunodeficiency virus (HIV). Even though topical BV therapy is used to varying degrees among countries, localized swelling or itching are common side effects that may occur in some patients. This review provides an in-depth analysis of the complex chemical composition of BV, highlighting the diverse range of bioactive compounds and their therapeutic applications, which extend beyond the well-known anti-inflammatory and pain-relieving effects, showcasing the versatility of BV in modern medicine. A specific search strategy was followed across various databases; Web of sciences, Scopus, Medline, and Google Scholar including in vitro and in vivo clinical studies.to outline an overview of BV composition, methods to use, preparation requirements, and Individual consumption contraindications. Furthermore, this review addresses safety concerns and emerging approaches, such as the use of nanoparticles, to mitigate adverse effects, demonstrating a balanced and holistic perspective. Importantly, the review also incorporates historical context and traditional uses, as well as a unique focus on veterinary applications, setting it apart from previous works and providing a valuable resource for researchers and practitioners in the field.

Balancing confidentiality and care coordination: challenges in patient privacy.

BACKGROUND: In the digital age, maintaining patient confidentiality while ensuring effective care coordination poses significant challenges for healthcare providers, particularly nurses. AIM: To investigate the challenges and strategies associated with balancing patient confidentiality and effective care coordination in the digital age. METHODS: A cross-sectional study was conducted in a general hospital in Egypt to collect data from 150 nurses across various departments with at least six months of experience in patient care. Data were collected using six tools: Demographic Form, HIPAA Compliance Checklist, Privacy Impact Assessment (PIA) Tool, Data Sharing Agreement (DSA) Framework, EHR Privacy and Security Assessment Tool, and NIST Cybersecurity Framework. Validity and Reliability were ensured through pilot testing and factor analysis. RESULTS: Participants were primarily aged 31-40 years (45%), with 75% female and 60% staff nurses. High compliance was observed in the HIPAA Compliance Checklist, especially in Administrative Safeguards (3.8 ± 0.5), indicating strong management and training processes, with an overall score of 85 ± 10. The PIA Tool showed robust privacy management, with Project Descriptions scoring 4.5 ± 0.3 and a total score of 30 ± 3. The DSA Framework had a mean total score of 20 ± 2, with Data Protection Measures scoring highest at 4.0 ± 0.4. The EHR assessments revealed high scores in Access Controls (4.4 ± 0.3) and Data Integrity Measures (4.3 ± 0.3), with an overall score of 22 ± 1.5. The NIST Cybersecurity Framework had a total score of 18 ± 2, with the highest scores in Protect (3.8) and lower in Detect (3.6). Strong positive correlations were found between HIPAA Compliance and EHR Privacy (r = 0.70, p < 0.05) and NIST Cybersecurity (r = 0.55, p < 0.05), reflecting effective data protection practices. CONCLUSION: The study suggests that continuous improvement in privacy practices among healthcare providers, through ongoing training and comprehensive privacy frameworks, is vital for enhancing patient confidentiality and supporting effective care coordination.

Comprehensive analysis of malabar tamarind fruit rind total extract: HPTLC fingerprinting, in-silico exploration of its metabolites for SARS-cov-2 omicron spike protein, antibacterial and antidiabetic potentials with in vitro evaluation of antidiabetic and antioxidant activities.

Malabar tamarind tropical fruit, scientifically known as Garcinia gummi-gutta, is indigenous to Southeast Asia. In this work, the total methanolic extract of the Malabar fruit rind was examined by HPTLC fingerprinting, with quantitative evaluation of the total phenolics and flavonoids. Library of previously reported natural metabolites was utilized to demonstrate their affinity for specific target sites, they were evaluated against Omicron SARS-CoV-2 mainly it's Spike Protein, bacterial tyrosinase, and antidiabetic targets such α-glucosidase, pancreatic lipase and also α-amylase enzymes. The molecular docking revealed that the Guttiferone R possessed the highest binding affinity toward the Omicron Spike Protein with a stable binding mode, -8.67 kcal/mol binding energy and a 1.07 Å RMSD value compared to reference, Azithromycin, which has -8.90 kcal/mol binding affinity and a 1.20 Å RMSD value. On the other hand, the identified polyphenolic compounds; Vitexin, Prunin, Naringin, Hinokiflavone, Kaempherol-3-O-rutinoside, Gallic acid, Naringenin, and Catechin, showed remarkable antidiabetic activity by strong inhibitory activity against α-glucosidase and notable activity against α-amylase compared with acarbose as reference. According to antibacterial activity, the identified compounds showed low affinity with weak activity against screened bacterial strains. In-vitro evaluation of Tamarind antioxidant and antidiabetic potentials, it exhibited a free radical-scavenging potential with 71.75 % retardation and α-glucosidase, α-amylase and pancreatic lipase inhibitor activities with an IC50 of 391.3 ± 26.27, 95.03 ± 0.03 and 0.01043 ± 0.0004 µg/mL, respectively that emphasize the molecular docking study. The findings imply that Malabar tamarind fruit rind possess antioxidant, antidiabetic, antibacterial and antiviral activities.

Novel Insights into the Antimicrobial and Antibiofilm Activity of Pyrroloquinoline Quinone (PQQ); In Vitro, In Silico, and Shotgun Proteomic Studies.

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.

Promoting effect of Sunset Yellow on N-methyl N-nitrosourea-induced rat mammary carcinogenesis: Implications of molecular mechanisms.

BACKGROUND: Nowadays, the use of food additives, such as Sunset Yellow (SY), is growing, which attracted attention to the potential relationship between some diseases and food additives. AIM: The study aimed to investigate the role of Sunset Yellow during chemically-induced mammary gland carcinogenesis in Sprague-Dawley rats. MATERIAL AND METHODS: Three groups of female rats were intraperitoneally administered with N-methyl-N-nitrosourea (MNU). Group 1 was set on a basal diet. Group 2 was treated with 161.4mg\kg\day Sunset Yellow (SY). Group 3 was given SY at 80.7mg\kg\day. Groups 4-6 were not administered MNU; Group 4 received vehicles only. Groups 5 and 6 were administered SY similarly to groups 2 and 3 respectively. RESULTS: Sunset Yellow at both doses exerted a significant dose-dependent increase in tumor incidences, multiplicities, volumes, and decreased tumor latency as compared with control. Immunolabeling indexes of the proliferating cell nuclear antigen, estrogen receptor alpha, and progesterone receptor were significantly increased after SY treatment. Oxidative stress markers, serum estrogen, progesterone, and prolactin levels were significantly modified by SY treatment. The mRNA expression of estrogen receptor alpha and epidermal growth factor was up-regulated in SY groups versus control. CONCLUSION: Collectively, SY has significantly promoted MNU-induced mammary tumors in rats with underlying mechanisms correlating SY consumption with estrogen disruption and subsequent antioxidative stress discrepancy.

Empagliflozin impact on experimentally induced acetaminophen toxicity: Imprint of mitochondrial dynamics, biogenesis, and cGAS/STING signal in amending liver insult.

Acetaminophen (APAP) is one of the most clinically relevant medications associated with acute liver damage. A prolific deal of research validated the hepatoprotective effect of empagliflozin (EMPA); however, its effect on APAP-induced hepatotoxicity has still not been investigated. In this study, the prospective hepatoprotective impact of EMPA against APAP-induced hepatotoxicity was investigated. Twenty-eight Balb-C mice were assigned to four groups: control, APAP, EMPA10/APAP, and EMPA25/APAP. At the end of the experiment, serum hepatotoxicity biomarkers, MDA level, and GSH content were estimated. Hepatic mitofusin-2 (MFN2), optic atrophy 1 (OPA1), dynamin-related protein 1 (Drp1), and mitochondrial fission 1 protein (FIS1) were immunoassayed. PGC-1α, cGAS, and STING mRNA expression were assessed by real-time PCR. Histopathological changes and immunohistochemistry of INF-ß, p-NF-κB, and iNOS were evaluated. APAP treatment caused significant hepatic functional impairment and increased hepatic MDA levels, as well as a concomitant decrease in GSH content. Marked elevation in Drp1 and FIS1 levels, INF-ß, p-NF-κB, and iNOS immunoreactivity, and reduction in MFN2 and OPA1 levels in the APAP-injected group, PGC-1α downregulation, and high expression of cGAS and STING were also documented. EMPA effectively ameliorated APAP-generated structural and functional changes in the liver, restored redox homeostasis and mitochondrial dynamics balance, and enhanced mitochondrial biogenesis, remarkably diminished hepatic expression of cGAS and STING, and elicited a reduction in hepatic inflammation. Moreover, the computational modeling data support the interaction of APAP with antioxidant system-related proteins as well as the interactions of EMPA against Drp1, cGAS, IKKA, and iNOS proteins. Our findings demonstrated for the first time that EMPA has an ameliorative impact against APAP-induced hepatotoxicity in mice via modulation of mitochondrial dynamics, biogenesis, and cGAS/STING-dependent inflammation. Thus, this study concluded that EMPA could be a promising therapeutic modality for acute liver toxicity.

The potential biological activities of Aspergillus luchuensis-aided green synthesis of silver nanoparticles.

Biosynthetic metals have attracted global attention because of their safety, affordability, and environmental friendliness. As a consequence, the cell-free filtrate (CFF) of Dill leaf-derived endophytic fungus Aspergillus luchuensis was employed for the extracellularly synthesis silver nanoparticles (AgNPs). A reddish-brown color shift confirmed that AgNPs were successfully produced. The obtained AgNPs were characterized by UV-Vis (ultraviolet-visible spectroscopy), Transmission electron microscopy (TEM), FTIR, EDX, and zeta potential. Results demonstrated the creation of crystalline AgNPs with a spherical shape at 427.81 nm in the UV-Vis spectrum, and size ranged from 16 to 18 nm as observed by TEM. Additionally, the biogenic AgNPs had a promising antibacterial activity versus multidrug-resistant bacteria, notably, S. aureus, E. coli, and S. typhi. The highest growth reduction was recorded in the case of E. coli. Furthermore, the biosynthesized AgNPs demonstrated potent antifungal potential versus a variety of harmful fungi. The maximum growth inhibition was evaluated from A. brasinsilles, followed by C. albicans as compared to cell-free extract and AgNO3. In addition, data revealed that AgNPs possess powerful antioxidant activity, and their ability to scavenge radicals increased from 33.0 to 85.1% with an increment in their concentration from 3.9 to 1,000 µg/mL. Furthermore, data showed that AgNPs displayed high catalytic activity of safranin under light irradiation. The maximum decolorization percentage (100%) was observed after 6 h. Besides, the biosynthesized AgNPs showed high insecticidal potential against 3rd larval instar of Culex pipiens. Taken together, data suggested that endophytic fungus, A. luchuensis, is an attractive candidate as an environmentally sustainable and friendly fungal nanofactory.

Multifaceted Impacts of Monosodium Glutamate on Testicular Health: Insights into Pyroptosis and Therapeutic Potential of Resveratrol.

BACKGROUND: Monosodium glutamate was considered one of the food additive and flavor enhancer in processed meat and soup that affects testicular tissues, the aim of this research to investigates the impact of monosodium glutamate (MSG) on testicular structure in rats and explores the potential protective effects of resveratrol. MATERIAL AND METHODS: Four experimental groups involved in our study 10 rats of each.: the first group as control group; the second group (Resveratrol group: control rats received 20 mg/kg of resveratrol, via oral gavage); the third group (MSG group: rats received monosodium glutamate (MSG) with a dose 60 mg/kg body weight daily, via gastric tube, and the fourth group (MSG+ Resveratrol group). Serum level of testosterone, FSH, LH, were measured. Testicular tissues were prepared for measurement of oxidative stress markers, and gene expression of NLRP3, Caspase 3, and GSK-3ß. Moreover, paraffin blocks contained testicular tissue used for histological and immunohistochemical examination. Additionally, seminal smear from epididymis were examined. RESULTS: MSG administration adversely affected testosterone production, hormonal levels, and sperm parameters, Histological examination revealed marked testicular degeneration, and oxidative stress assessments indicated elevated level of MDA a lipid peroxidation marker and decrease in SOD, CAT antioxidant enzymes. Moreover, MSG-induced apoptotic and pyroptotic markers and its gene expressions. Importantly. Administration of resveratrol reversed the detrimental effects of MSG, demonstrating its corrective influence on the hypothalamic-pituitary-gonadal axis disruption, improvement of sperm parameters, attenuation of oxidative stress, anti-apoptotic activity, and anti-pyroptotic effects. The expression of Ki-67 as a cell proliferation marker further supported the positive response to spermatogenesis dysfunction upon resveratrol treatment. CONCLUSIONS: This comprehensive exploration sheds light on the protective effect of resveratrol against MSG-induced testicular with exploration of its mechanistic role.

Effect of autologous platelet-rich plasma on the fertility and quality of cryopreserved buffalo bull semen: a comparative study using OptiXcell® and tris egg yolk extenders.

BACKGROUND: Buffalo spermatozoa have a distinct membrane structure that makes them more vulnerable to cryopreservation, resulting in lower-quality post-thawed sperm. This decreases the success rate of artificial insemination in buffaloes. Understanding and addressing these specific vulnerabilities are essential for improving reproductive techniques in buffalo populations. The properties of cryopreserved buffalo bull semen were examined in this study regarding the impact of adding autologous platelet-rich plasma (PRP) to OptiXcell® or Tris egg yolk-based extenders. Ten buffalo bulls were used to collect semen. Each bull's ejaculate was separated into two main equal amounts, each of which was then diluted with either OptiXcell® or Tris egg yolk-based extender, supplemented with various PRP concentrations (5%, 10%, and 15%), and the control (0%), before being cryopreserved according to established protocols. Following equilibration and thawing, the quality and functionality of the sperm were evaluated, along with the antioxidant enzyme activities (GSH and TAC), malondialdehyde (MDA) content, and in vivo fertilization rate of the thawed semen. RESULTS: All PRP concentrations in both extenders, particularly 10% PRP, improved the quality and functionality of the sperm in both equilibrated and frozen-thawed semen. Additionally, the antioxidant enzyme activities in both extenders were higher in the PRP-supplemented groups compared to the control group in thawed semen (P < 0.05). All post-thaw sperm quality, antioxidant enzyme activities, and functionality aside from DNA integrity were higher (P < 0.05) in the PRP-supplemented OptiXcell® than in the PRP-supplemented Tris egg yolk-based extender. The fertility of cryopreserved semen in the extenders supplemented with 10% and 15% PRP increased (P < 0.05) significantly more than that of the control extenders, with 10% PRP being the optimum concentration in OptiXcell® (80%) compared to that of Tris egg yolk-based extender (66.67%) and control of two extenders (53.33% and 46.67%, respectively). CONCLUSIONS: Even though autologous PRP-supplemented extenders have a protective impact on equilibrated and cryopreserved semen, 10% PRP-supplemented OptiXcell® extenders are more effective at preserving post-thaw semen quality, functionality, and antioxidant capacity, which increases the in vivo fertility of buffalo bulls.

Bioactive injectable mucoadhesive thermosensitive natural polymeric hydrogels for oral bone and periodontal regeneration.

Periodontitis is an inflammation-related condition, caused by an infectious microbiome and host defense that causes damage to periodontium. The natural processes of the mouth, like saliva production and eating, significantly diminish therapeutic medication residency in the region of periodontal disease. Furthermore, the complexity and diversity of pathological mechanisms make successful periodontitis treatment challenging. As a result, developing enhanced local drug delivery technologies and logical therapy procedures provides the foundation for effective periodontitis treatment. Being biocompatible, biodegradable, and easily administered to the periodontal tissues, hydrogels have sparked substantial an intense curiosity in the discipline of periodontal therapy. The primary objective of hydrogel research has changed in recent years to intelligent thermosensitive hydrogels, that involve local adjustable sol-gel transformations and regulate medication release in reaction to temperature, we present a thorough introduction to the creation and efficient construction of new intelligent thermosensitive hydrogels for periodontal regeneration. We also address cutting-edge smart hydrogel treatment options based on periodontitis pathophysiology. Furthermore, the problems and prospective study objectives are reviewed, with a focus on establishing effective hydrogel delivery methods and prospective clinical applications.

Prospectives and challenges of nano-tailored biomaterials-assisted biological molecules delivery for tissue engineering purposes.

Nano carriers have gained more attention for their possible medical and technological applications. Tailored nanomaterials can transport medications efficiently to targeted areas and allow for sustained medication discharge, reducing undesirable toxicities while boosting curative effectiveness. Nonetheless, transitioning nanomedicines from experimental to therapeutic applications has proven difficult, so different pharmaceutical incorporation approaches in nano scaffolds are discussed. Then numerous types of nanobiomaterials implemented as carriers and their manufacturing techniques are explored. This article is also supported by various applications of nanobiomaterials in the biomedical field.

Tapping the biosynthetic potential of marine Bacillus licheniformis LHG166, a prolific sulphated exopolysaccharide producer: structural insights, bio-prospecting its antioxidant, antifungal, antibacterial and anti-biofilm potency as a novel anti-infective lead.

The escalating global threat of antimicrobial resistance necessitates prospecting uncharted microbial biodiversity for novel therapeutic leads. This study mines the promising chemical richness of Bacillus licheniformis LHG166, a prolific exopolysaccharide (EPSR2-7.22 g/L). It comprised 5 different monosaccharides with 48.11% uronic acid, 17.40% sulfate groups, and 6.09% N-acetyl glucosamine residues. EPSR2 displayed potent antioxidant activity in DPPH and ABTS+, TAC and FRAP assays. Of all the fungi tested, the yeast Candida albicans displayed the highest susceptibility and antibiofilm inhibition. The fungi Aspergillus niger and Penicillium glabrum showed moderate EPSR2 susceptibility. In contrast, the fungi Mucor circinelloides and Trichoderma harzianum were resistant. Among G+ve tested bacteria, Enterococcus faecalis was the most susceptible, while Salmonella typhi was the most sensitive to G-ve pathogens. Encouragingly, EPSR2 predominantly demonstrated bactericidal effects against both bacterial classes based on MBC/MIC of either 1 or 2 superior Gentamicin. At 75% of MBC, EPSR2 displayed the highest anti-biofilm activity of 88.30% against B. subtilis, while for G-ve antibiofilm inhibition, At 75% of MBC, EPSR2 displayed the highest anti-biofilm activity of 96.63% against Escherichia coli, Even at the lowest dose of 25% MBC, EPSR2 reduced biofilm formation by 84.13% in E. coli, 61.46% in B. subtilis. The microbial metabolite EPSR2 from Bacillus licheniformis LHG166 shows promise as an eco-friendly natural antibiotic alternative for treating infections and oxidative stress.

Consumption of aphrodisiac drugs without prescription among men in Saudi Arabia: cross-sectional study.

Background: The prevalence and patterns of aphrodisiac drug consumption without prescription among men in Saudi Arabia remain underexplored, with limited empirical evidence available. Given the potential health implications and societal considerations, a comprehensive investigation is warranted. Aim: Assess the Prevalence, pattern of use and the associated factors of Aphrodisiac drugs consumption without prescription among men at Najran City, Saudi Arabia. Methods: Employing a cross-sectional descriptive study, 500 participants were included through convenience sampling. The utilized questionnaires covered a range of data, including socio-demographic information, patterns of aphrodisiac use, knowledge about aphrodisiacs, lifestyle details, a sexual health inventory for men, and a perceived stress level scale. Results: The study reveals a significant prevalence of unsanctioned aphrodisiac drug use (31%) among men in Najran City, Saudi Arabia, with a majority (79.3%) consuming these substances four times monthly. Associated disparities in knowledge, lifestyle, stress, and sexual function underscore the urgent need for policy interventions and tailored health education initiatives for this demographic. Conclusion: Approximately one-third of the sampled population engaged in the unsanctioned use of aphrodisiac drugs, with the majority utilizing them four times monthly. Tablets emerged as the most prevalent form of consumption. Commonly cited motives and justifications included peer influence and the perceived safety of aphrodisiacs. Influential factors encompassed levels of knowledge, lifestyle, stress levels, erectile function, age, education, and the number of wives. Recommendations: Urgent policy interventions are warranted to regulate the acquisition and distribution of aphrodisiacs. Tailored health education initiatives should be implemented for married and prospective married men.

Anti-proliferative activity of RIHMS-Qi-23 against MCF-7 breast cancer cell line is through inhibition of cell proliferation and senescence but not inhibition of targeted kinases.

BACKGROUND: Breast cancer is the most common malignancy globally, and is considered a major cause of cancer-related death. Tremendous effort is exerted to identify an optimal anticancer drug with limited side effects. The quinoline derivative RIMHS-Qi-23 had a wide-spectrum antiproliferative activity against various types of cancer cells. METHODS: In the current study, the effect of RIMHS-Qi-23 was tested on MCF-7 breast cancer cell line to evaluate its anticancer efficacy in comparison to the reference compound doxorubicin. RESULTS: Our data suggest an anti-proliferative effect of RIMHS-Qi-23 on the MCF-7 cell line with superior potency and selectivity compared to doxorubicin. Our mechanistic study suggested that the anti-proliferative effect of RIMHS-Qi-23 against MCF-7 cell line is not through targeted kinase inhibition but through other molecular machinery targeting cell proliferation and senescence such as cyclophlin A, p62, and LC3. CONCLUSION: RIMHS-Qi-23 is exerting an anti-proliferative effect that is more potent and selective than doxorubicin.

Nootkatone Mitigated Melamine-Evoked Hepatotoxicity by Featuring Oxidative Stress and Inflammation Interconnected Mechanisms: In Vivo and In Silico Approaches.

Melamine (ML) is a common environmental contaminant, commonly used in food fraud, representing a serious health hazard and jeopardizing human and animal health. Recently, nootkatone (NK), a naturally occurring sesquiterpenoid, has garnered considerable attention due to its potential therapeutic advantages. We investigated the potential mechanisms underlying the protective effects of NK against ML-induced liver injury in rats. Five groups were utilized: control, ML, NK10, ML-NK5, and ML-NK10. ML induced substantial hepatotoxicity, including considerable alterations in biochemical parameters and histology. The oxidative distress triggered by ML increased the generation of malondialdehyde (MDA) and nitric oxide (NO) and decreased levels of reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. In addition, decreased expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased nuclear factor kappa beta (NF-κB) expression levels were observed in hepatocytes, which indicated the occurrence of inflammatory changes following ML exposure. These alterations were alleviated by NK supplementation in a dose-dependent manner. The data revealed that the favorable effects of NK were attributed, at least in part, to its antioxidant and anti-inflammatory properties. Moreover, our results were supported by molecular docking studies that revealed a good fit and interactions between NK and antioxidant enzymes. Thus, the current study demonstrated that NK is a potential new food additive for the prevention or treatment of ML-induced toxicity.

Cardioprotective effect of abscisic acid in a rat model of type 3 cardio-renal syndrome: Role of NOX-4, P-53, and HSP-70.

Cardiorenal syndrome (CRS) is a complex heart and kidney pathophysiologic disorder that leads to a bidirectional interrelationship between them. Abscisic acid (ABA) is a phytohormone that is present in plants, and is known to regulate fundamental physiological functions. This study aimed to explore the efficacy of ABA in surgically induced-CRS type 3 rats. Rats were randomly and equally divided into four groups. Rats in Group 1 received saline (Sham group), Group 2 included control induced-CRS rats, Group 3 rats (CRS+ABA) included CRS rats treated with ABA and Group 4 (CRS + ABA + Verapamil + propofol) were CRS rats treated with Verapamil, propofol and ABA. The rats were treated with the drugs daily for four weeks. At the end of the study, relative heart weight corrected QT interval (QTc), mean blood pressure (MBP), kidney functions, oxidative stress, NADPH oxidase 4 (NOX4), protein 53 (P53), and heat shock proteins-70 (HSP-70) expression was assessed and recorded. ABA led to a significant shortening of the ventricular action potential duration indicated by QTc. Furthermore, it significantly lowered heart weight, MBP, serum creatinine, NOX-4, and P-53 expression and augmented HSP-70 expression. In contrast, adding calcium channel blockers (CCBs) to ABA mitigated this effect. The results suggested that ABA has a potential protective role in CRS-induced cardiac hypertrophy and arrhythmia that could be mediated through inhibition of P-53, NOX-4, and an increase in HSP-70 expression.

Antibiotic action and resistance: updated review of mechanisms, spread, influencing factors, and alternative approaches for combating resistance.

Antibiotics represent a frequently employed therapeutic modality for the management of bacterial infections across diverse domains, including human health, agriculture, livestock breeding, and fish farming. The efficacy of antibiotics relies on four distinct mechanisms of action, which are discussed in detail in this review, along with accompanying diagrammatic illustrations. Despite their effectiveness, antibiotic resistance has emerged as a significant challenge to treating bacterial infections. Bacteria have developed defense mechanisms against antibiotics, rendering them ineffective. This review delves into the specific mechanisms that bacteria have developed to resist antibiotics, with the help of diagrammatic illustrations. Antibiotic resistance can spread among bacteria through various routes, resulting in previously susceptible bacteria becoming antibiotic-resistant. Multiple factors contribute to the worsening crisis of antibiotic resistance, including human misuse of antibiotics. This review also emphasizes alternative solutions proposed to mitigate the exacerbation of antibiotic resistance.

Gasdermin D: A potential mediator and prognostic marker of bladder cancer.

Background: Bladder cancer is considered one of the commonest widespread cancers, its presentation ranges from non-muscle invasive form to being muscle-invasive. The gasdermin family of proteins consists of six proteins. Members of gasdermin family are involved in pyroptosis; which is considered as type of inflammatory apoptosis via participation of gasdermin D and inflammatory caspases. Purpose: The goal of this research was to look into the potential involvement of gasdermin D in pathogenesis of bladder cancer, In addition, to investigate its potential role as a prognostic marker of bladder cancer. Methods: Gasdermin D gene and protein expression was examined in fresh frozen 80 bladder cancer specimens (30 NMIBC, and 50 MIBC) and the matching 80 control tissue samples utilizing real-time polymerase chain reaction and western blotting. Furthermore, the immunoreactivity of gasdermin D protein was also detected by immunohistochemistry. Results: Gasdermin D gene and protein expression showed a highly significant difference between the control and the two bladder cancer groups (p < 0.001), as demonstrated by real-time PCR, western blotting and immunohistochemistry. Cox proportional hazards regression models showed that lower gasdermin D gene expression in cancer patients (≤1.58-fold), and younger age (≤53 years) were linked with a higher risk of local tumor recurrence. Moreover, higher gasdermin D gene expression (>2.18-fold), and lymph nodes' involvement were associated with an increased mortality. Conclusion: Gasdermin D is involved in the pathogenesis of bladder cancer and muscle invasion, in addition, tissue gasdermin D expression may be used as useful tool to predict local tumor recurrence.

Targeting Hydrogen Sulfide Modulates Dexamethasone-Induced Muscle Atrophy and Microvascular Rarefaction, through Inhibition of NOX4 and Induction of MGF, M2 Macrophages and Endothelial Progenitors.

Long-term use of Glucocorticoids produces skeletal muscle atrophy and microvascular rarefaction. Hydrogen sulfide (H2S) has a potential role in skeletal muscle regeneration. However, the mechanisms still need to be elucidated. This is the first study to explore the effect of Sodium hydrosulfide (NaHS) H2S donor, against Dexamethasone (Dex)-induced soleus muscle atrophy and microvascular rarefaction and on muscle endothelial progenitors and M2 macrophages. Rats received either; saline, Dex (0.6 mg/Kg/day), Dex + NaHS (5 mg/Kg/day), or Dex + Aminooxyacetic acid (AOAA), a blocker of H2S (10 mg/Kg/day) for two weeks. The soleus muscle was examined for contractile properties. mRNA expression for Myostatin, Mechano-growth factor (MGF) and NADPH oxidase (NOX4), HE staining, and immunohistochemical staining for caspase-3, CD34 (Endothelial progenitor marker), vascular endothelial growth factor (VEGF), CD31 (endothelial marker), and CD163 (M2 macrophage marker) was performed. NaHS could improve the contractile properties and decrease oxidative stress, muscle atrophy, and the expression of NOX4, caspase-3, Myostatin, VEGF, and CD31 and could increase the capillary density and expression of MGF with a significant increase in expression of CD34 and CD163 as compared to Dex group. However, AOAA worsened the studied parameters. Therefore, H2S can be a promising target to attenuate muscle atrophy and microvascular rarefaction.