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BACKGROUND: Mercuric chloride (HgCl2) is poisonous to humans and animals and typically damages the nervous system and other organs. Mercuric chloride exposition disclosed to initiation of oxidative stress pathway can result in a defect in male fertility and testis tissue. Synthesized selenium nanoparticles (SeNPs) were characterized with a diameter range minimal than 100 nm, having the effective sets of the biological matter. The present study aimed to evaluate the effect of biosynthesized SeNPs, prepared by leek extract on Wistar rats' testicles and brain. METHODS: Thirty‐five Wistar male rats (120–150 g) were randomly split into five groups (n = 7), orally ingested with leek aqueous extract loaded on SeNPs, and then the animals were administered with mercury II chloride (HgCl2) to induce testis injury and damage the nervous system. RESULTS: The used dose of mercuric chloride led to oxidative stress damage in the testis of the rats which was evidenced by a decrease in testosterone, luteinizing hormone (LH), follicle‐stimulating hormone (FSH) and proliferating cell nuclear antigen (PCNA) levels, and an increase in nuclear factor‐kappa B (NF‐κB) and caspase‐3. Also, HgCl2 decreased the levels of dopamine (DA), serotonin (5‐HT), norepinephrine (NE) and brain‐derived neurotrophic factor (BDNF) in the brains of rats. In addition, A decrease was observed in the levels of antioxidant markers, B‐cell lymphoma‐2 (Bcl‐2), as well as an increase in malondialdehyde (MDA), nitric oxide (NO), NF‐κB, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β and Bax in both testes and brains. Pre‐treatment with leek extract loaded on SeNPs significantly ameliorated testosterone, LH, FSH, PCNA and caspase‐3 levels in the testis and DA, 5‐HT, NE and BDNF in brains. Although the contents of MDA, NO, TNF‐α, IL‐1β, NF‐κB and Bax decreased significantly in both. glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and Bcl‐2 levels were significantly improved in both organs. CONCLUSION: Our findings suggest that treatment with aqueous leek extract loaded on SeNPs may offer promising prospects for the advancement of anti‐inflammation activity against testis injury and also have a very key role in neurobehavioral alterations as a result of mercury toxicity. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Instinctive gastrointestinal inflammatory conditions with persistent intestinal inflammation are known as "inflammatory bowel diseases" (IBDs). IBDs are growing progressively common throughout the world although it is still unclear what causes them. IBDs that cause recurrent, intermittent, and disburse inflammatory responses, may also have systemic symptoms such as ulcerative colitis and Crohn's disease. It has been discovered that a number of medications, including antibiotics, corticosteroids, and immune-suppressants, can promote mucous and damaged epithelial restoration. The incidences of general and specific therapy failure in IBD continue to climb, even though the availability of advanced biologics including anti-interleukins, anti-integrins, anti-tumor necrosis factor (anti-TNF), and small molecules such as tofacitinib exist. Management therapies that are currently being researched include specifically JAK (janus kinase) inhibitors, anti-IL (anti-interleukin) (IL-12, IL23), and leukocyte inhibitors such as sphingosine-1-phosphate receptors. Clinical treatments can have various adverse effects. In order to give pharmacological drugs to the disease-specific sites with improved efficacy and fewer complications, innovative frameworks centered on biomaterials are needed. We provide an outlook on the current state of several biomaterials used to treat IBD. This article comprehensively addresses numerous microparticles, nanoparticles, and hydrogels that have recently been made from natural bio-polymers and lipids. To support colon-specific target delivery and steady release of medications during IBD therapies, these various biomaterial-based monotherapies could be employed as efficient drug delivery systems. [ABSTRACT FROM AUTHOR]

The RAS gene family is one of the most frequently mutated oncogenes in human cancers. In KRAS, mutations of G12D and G12C are common. Here, 52 iridoids were selected and docked against 8AFB (KRAS G12C receptor) using Sotorasib as the standard. As per the docking interaction data, 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester (dock score: −9.9 kcal/mol), 6′-O-trans-para-coumaroyl geniposidic acid (dock score: −9.6 kcal/mol), 6-O-trans-cinnamoyl-secologanoside (dock score: −9.5 kcal/mol), Loganic acid 6′-O-beta-d-glucoside (dock score: −9.5 kcal/mol), 10-O-succinoylgeniposide (dock score: −9.4), Loganic acid (dock score: −9.4 kcal/mol), and Amphicoside (dock score: −9.2 kcal/mol) showed higher dock scores than standard Sotorasib (dock score: −9.1 kcal/mol). These common amino acid residues between iridoids and complexed ligands confirmed that all the iridoids perfectly docked within the receptor's active site. The 100 ns MD simulation data showed that RMSD, RMSF, radius of gyration, and SASA values were within range, with greater numbers of hydrogen bond donors and acceptors. MM/PBSA analysis showed maximum binding energy values of −7309 kJ/mol for 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester. FMO analysis showed that 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester was the most likely chemically reactive molecule. MEP analysis data highlighted the possible electrophilic and nucleophilic attack regions of the best-docked iridoids. Of all the best-docked iridoids, Loganic acid passed Lipinski, Pfizer, and GSK filters with a similar toxicity profile to Sotorasib. Thus, if we consider these iridoids to be KRAS G12C inhibitors, they will be a boon to mankind. [ABSTRACT FROM AUTHOR]

Nucleocapsid protein (N) of SARS-CoV-2 is a multivalent protein, which is responsible for viral replication, assembly, packaging and modulates host immune response. In this study, we report conformational measurements of N protein at different pH by observing transition in secondary and tertiary structural contents by biophysical and computational approaches. Spectroscopic measurements revealed that N protein loses its secondary and tertiary structure at extreme acidic pH while maintaining its native conformation at mild acidic and alkaline pH. Molecular dynamics simulation studies validated spectroscopic findings. Secondary structure estimation confirmed circular dichroism (CD) findings that participation of total number of average residues in formation of native structure is higher at physiological pH, and coil percentage is higher at acidic pH. In molten globule (MG) state, secondary structure is conserved but here, CD data reveal more random structure at low pH. In pre-MG, ANS (8-anilino-1-napthalene sulfonate) binds weakly to protein as compared to MG but here, ANS binds strongly to protein. All the above-mentioned findings suggested formation of intermediary like state at low pH, which can be attributed to an off-pathway species. Unravelling structural characteristics of N protein will help understand phase-separation, protein-protein interaction and host-immune response modulation behaviour, which will eventually help in designing novel therapeutic target against COVID-19.

Programmed cell death ligand 1 (PD-L1) is a crucial target for cancer therapy. Here, an in silico study investigates PD-L1 to inhibit its interaction with PD1, thereby promoting an immune response to eliminate cancer cells. The study employed machine learning (ML) -based QSAR to detect PDL1 inhibitors. Morgan's fingerprint with docking score showed a 0.83 correlation with the experimental IC50, enabling the screening of 3200 natural compounds. The top three compounds, considered 2819 , 2821 and 3188 , were selected from the ML-based QSAR and subjected to molecular docking and simulation. The binding scores for 2819 , 2821 and 3188 were -7.0, -9.0 and -8.9 kcal/mol, respectively. The stability of the ligands during a 100 ns simulation was assessed using RMSD, showing that 2819 and 2821 maintained stable patterns comparable to the control inhibitor. Notably, 2819 exhibited a consistent stable pattern throughout the simulation, while 2821 showed stability in the last 40 ns. The control compound showed the highest number of hydrogen bonds with proteins, whereas compounds 2819 and 2821 formed continuous H-bonds. 3188 was separated from the protein in later phases and is not regarded as a potential PD-L1-binding molecule. MMGBSA binding free energy for complexes was computed. Control had the lowest binding free energy, while 2819 and 2821 also had lower binding energies. In contrast, 3188 showed poor binding free energy, causing protein separation. Principal component analysis showed a loss of entropy and reduced protein conformational variation. Overall, 2819 and 2821 are potential binders for PD-L1 inhibition and immune response triggering.Communicated by Ramaswamy H. Sarma.

The efficacy of 40 bacterial isolates obtained from hot spring water samples to produce cellulase enzymes was investigated. As a result, the strain Bacillus subtilis F3, which was identified using traditional and molecular methods, was selected as the most potent for cellulase production. Optimization was carried out using one-factor-at-a-time (OFAT) and BOX-Behnken Design to detect the best conditions for the highest cellulase activity. This was accomplished after an incubation period of 24 h at 45°C and pH 8, with an inoculum size of 1% (v/v), 5 g/l of peptone as nitrogen source, and 7.5 g/l of CMC. Moreover, the best concentration of ammonium sulfate for cellulase enzyme precipitation was 60% followed by purification using a dialysis bag and Sephadex G-100 column chromatography to collect the purified enzyme. The purified cellulase enzyme was characterized by 5.39-fold enrichment, with a specific activity of 54.20 U/mg and a molecular weight of 439 kDa. There were 15 amino acids involved in the purified cellulase, with high concentrations of 160 and 100 mg/l for glycine and proline respectively. The highest stability and activity of the purified cellulase was attained at pH 7 and 50°C in the presence of 150 ppm of CaCl 2 , NaCl, and ZnO metal ions. Finally, the biopolishing activity of the cellulase enzyme, as indicated by weight loss percentages of the cotton fabric, was dependent on concentration and treatment time. Overall, the thermotolerant B. subtilis F3 strain has the potential to provide highly stable and highly active cellulase enzyme for use in biopolishing of cotton fabrics.