Antifungal Activity of Juglans-regia-Mediated Silver Nanoparticles (AgNPs) against Aspergillus-ochraceus-Induced Toxicity in In Vitro and In Vivo Settings.

Aflatoxins produced by some species of Aspergillus are considered secondary toxic fungal by-products in feeds and food. Over the past few decades, many experts have focused on preventing the production of aflatoxins by Aspergillus ochraceus and also reducing its toxicity. Applications of various nanomaterials in preventing the production of these toxic aflatoxins have received a lot of attention recently. The purpose of this study was to ascertain the protective impact of Juglans-regia-mediated silver nanoparticles (AgNPs) against Aspergillus-ochraceus-induced toxicity by exhibiting strong antifungal activity in in vitro (wheat seeds) and in vivo (Albino rats) settings. For the synthesis of AgNPs, the leaf extract of J. regia enriched with high phenolic (72.68 ± 2.13 mg GAE/g DW) and flavonoid (18.89 ± 0.31 mg QE/g DW) contents was used. Synthesized AgNPs were characterized by various techniques, including TEM, EDX, FT-IR, and XRD, which revealed that the particles were spherical in shape with no agglomeration and fine particle size in the range of 16-20 nm. In vitro antifungal activity of AgNPs was tested on wheat grains by inhibiting the production of toxic aflatoxins by A. ochraceus. According to the results obtained from High-Performance Liquid Chromatography (HPLC) and Thin-Layer Chromatography (TLC) analyses, there was a correlation between the concentration of AgNPs and a decrease in the production of aflatoxin G1, B1, and G2. For in vivo antifungal activity, Albino rats were administrated with different doses of AgNPs in five groups. The results indicated that the feed concentration of 50 µg/kg feed of AgNPs was more effective in improving the disturbed levels of different functional parameters of the liver (alanine transaminase (ALT): 54.0 ± 3.79 U/L and aspartate transaminase (AST): 206 ± 8.69 U/L) and kidney (creatinine 0.49 ± 0.020 U/L and BUN 35.7 ± 1.45 U/L), as well as the lipid profile (LDL 22.3 ± 1.45 U/L and HDL 26.3 ± 2.33 U/L). Furthermore, the histopathological analysis of various organs also revealed that the production of aflatoxins was successfully inhibited by AgNPs. It was concluded that the harmful effects of aflatoxins produced by A. ochraceus can be successfully neutralized by using J. regia-mediated AgNPs.

In Silico Structural and Functional Analyses of NLRP3 Inflammasomes to Provide Insights for Treating Neurodegenerative Diseases.

Inflammasomes are cytoplasmic intracellular multiprotein complexes that control the innate immune system's activation of inflammation in response to derived chemicals. Recent advancements increased our molecular knowledge of activation of NLRP3 inflammasomes. Although several studies have been done to investigate the role of inflammasomes in innate immunity and other diseases, structural, functional, and evolutionary investigations are needed to further understand the clinical consequences of NLRP3 gene. The purpose of this study is to investigate the structural and functional impact of the NLRP3 protein by using a computational analysis to uncover putative protein sites involved in the stabilization of the protein-ligand complexes with inhibitors. This will allow for a deeper understanding of the molecular mechanism underlying these interactions. It was found that human NLRP3 gene coexpresses with PYCARD, NLRC4, CASP1, MAVS, and CTSB based on observed coexpression of homologs in other species. The NACHT, LRR, and PYD domain-containing protein 3 is a key player in innate immunity and inflammation as the sensor subunit of the NLRP3 inflammasome. The inflammasome polymeric complex, consisting of NLRP3, PYCARD, and CASP1, is formed in response to pathogens and other damage-associated signals (and possibly CASP4 and CASP5). Comprehensive structural and functional analyses of NLRP3 inflammasome components offer a fresh approach to the development of new treatments for a wide variety of human disorders.

Implication of Nanoparticles to Combat Chronic Liver and Kidney Diseases: Progress and Perspectives.

Liver and kidney diseases are the most frequently encountered problems around the globe. Damage to the liver and kidney may occur as a result of exposure to various drugs, chemicals, toxins, and pathogens, leading to severe disease conditions such as cirrhosis, fibrosis, hepatitis, acute kidney injury, and liver and renal failure. In this regard, the use of nanoparticles (NPs) such as silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), and zinc oxide nanoparticles (ZnONPs) has emerged as a rapidly developing field of study in terms of safe delivery of various medications to target organs with minimal side effects. Due to their physical characteristics, NPs have inherent pharmacological effects, and an accidental buildup can have a significant impact on the structure and function of the liver and kidney. By suppressing the expression of the proinflammatory cytokines iNOS and COX-2, NPs are known to possess anti-inflammatory effects. Additionally, NPs have demonstrated their ability to operate as an antioxidant, squelching the generation of ROS caused by substances that cause oxidative stress. Finally, because of their pro-oxidant properties, they are also known to increase the level of ROS, which causes malignant liver and kidney cells to undergo apoptosis. As a result, NPs can be regarded as a double-edged sword whose inherent therapeutic benefits can be refined as we work to comprehend them in terms of their toxicity.

Genomic analysis of arginine vasopressin gene in riverine buffalo reveals its potential association with silent estrus behavior.

BACKGROUND: Poor estrus expression behavior causes suboptimal reproductive efficiency through poor conception rate. Various signaling pathways are involved in estrus expression but arginine vasopressin (AVP) gene with oxytocin predominantly regulates estrus behavior. This study aimed to perform genomic characterization and evolutionary dynamics of AVP gene through association testing of the novel polymorphic loci and comparative genomic analysis to explore the potential effect of AVP gene on estrus behavior of Nili-Ravi buffaloes. METHODS AND RESULTS: 198 Nili-Ravi buffaloes were screened for the quest of novel polymorphism in the AVP gene. In exon-1, five polymorphic sites were detected including deletion of two (c.47delA and c.57delA) nucleotides that caused drastic variation in subsequent amino acid sequence due to frame shift including functional short peptide of nine residues. The 3-D structure revealed a loss of transmembrane loop between 16 and 31 residues in Nili-Ravi buffalo AVP protein sequence, suggesting that missing loop apparently reduced the gene functionality in Nili-Ravi buffalo by inhibiting cellular reactions and muting the animal estrus cyclicity. Three polymorphisms detected in AVP gene were significantly associated with silent estrus (P < 0.05). The comparative genomic analysis revealed that AVP gene is present on chromosome 14 having one conserved motif (Neurohypophysial) in buffalo. CONCLUSIONS: This study suggested the potential use of polymorphic sites as promising genetic markers for selection of buffaloes with pronounced estrus expression.