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.

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.

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.

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.

DNA Polymorphisms and mRNA Levels of Immune Biomarkers as Candidates for Inflammatory Postpartum Disorders Susceptibility in Italian Buffaloes.

The immunological genes that may interact with inflammatory postpartum diseases in Italian buffaloes were examined in this study. A total number of 120 female Italian buffaloes (60 normal and 60 with inflammatory reproductive diseases) were employed. Each buffalo's jugular vein was pierced to get five milliliters of blood. To obtain whole blood and extract DNA and RNA, the blood was placed within tubes containing sodium fluoride or EDTA anticoagulants. The immunological (IKBKG, LGALS, IL1B, CCL2, RANTES, MASP2, HMGB1, and S-LZ) genes' nucleotide sequence differences between healthy buffaloes and buffaloes affected by inflammatory reproductive diseases were found by employing PCR-DNA sequencing. According to Fisher's exact test (p ˂ 0.01), there were noticeably different probabilities of all major nucleotide changes spreading among buffalo groups with and without reproductive problems. Buffaloes were significantly more likely to express the examined genes when they had inflammatory reproductive diseases. The outcomes might support the significance of these markers' nucleotide variations and gene expression patterns as indicators of the prevalence of inflammatory reproductive disorders and provide a workable buffalo management policy.

Microalgae (Chlorella vulgaris) attenuates aflatoxin-associated renal injury.

Introduction: Aflatoxins (AFT) are ubiquitous environmental pollutants that are extremely dangerous for both human beings as well as animals. A safe, effective, and considerate strategy is therefore credited with controlling AFT intoxication. Therefore, our study aimed to evaluate the mitigating properties of Chlorella vulgaris (ChV) against AFT-induced nephrotoxicity and altered egg quality. Methods: Quails were randomized into Control group (receiving a normal diet); ChV group (1 g/kg diet); AFT group (receiving an AFT-containing diet); and the AFT-ChV group were given both treatments. Results and discussion: AFT provoked kidney injury, exhibited by increased renal biochemical parameters and reduced protein levels. Malondialdehyde (MDA) levels dramatically increased as a consequence of AFT exposure, and glutathione (GSH) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were also decreased. Substantial up-modulation of the mRNA expression of the inflammatory cytokines (TNF-α, IL-1ß, and IL-6) was additionally reported. Furthermore, AFT residues were detected in the egg compromising its quality and nutritional value. Contrarily, ChV supplemented diet suppressed the AFT-prompted oxidative stress and inflammation, together with enhancing the nutritional value and quality of eggs and decreasing AFT residues. These beneficial impacts are proposed to be attributed to its antioxidant and nutritional ingredients. The molecular docking dynamics confirmed the inflammatory and apoptotic protein targets for ChV. Our findings recommend that adding ChV supplements to foods might guard against nephrotoxicity brought on by AFT exposure.