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The development of nanomaterials has been speedily established in recent years, yet nanoparticles synthesized by traditional methods suffer unacceptable toxicity and the sustainability of the procedure for synthesizing such nanoparticles is inadequate. Consequently, green biosynthesis, which employs biopolymers, is gaining attraction as an environmentally sound alternative to less sustainable approaches. Chitosan-encapsulated nanoparticles exhibit exceptional antibacterial properties, offering a wide range of uses. Chitosan, obtained from shrimp shells, aided in the environmentally friendly synthesis of high-purity zinc oxide nanoparticles (ZnO NPs) with desirable features such as the extraction yield (41%), the deacetylation (88%), and the crystallinity index (74.54%). The particle size of ZnO NPs was 12 nm, while that of chitosan–ZnO NPs was 21 nm, and the bandgap energies of these nanomaterials were 3.98 and 3.48, respectively. The strong antibacterial action was demonstrated by ZnO NPs, chitosan–ZnO NPs, and chitosan–ZnO/PVP, particularly against Gram-positive bacteria, making them appropriate for therapeutic use. The photocatalytic degradation abilities were also assessed for all nanoparticles. At a concentration of 6 × 10 –5  M, chitosan removed 90.5% of the methylene blue (MB) dye, ZnO NPs removed 97.4%, chitosan-coated ZnO NPs removed 99.6%, while chitosan–ZnO/PVP removed 100%. In the case of toluidine blue (TB), at a concentration of 4 × 10 –3  M, the respective efficiencies were 96.8%, 96.8%, 99.5%, and 100%, respectively. Evaluation of radical scavenger activity revealed increased scavenging of ABTS and DPPH radicals by chitosan–ZnO/PVP compared to individual zinc oxide or chitosan–ZnO, where the IC50 results were 0.059, 0.092, 0.079 mg/mL, respectively, in the ABTS test, and 0.095, 0.083, 0.061, and 0.064 mg/mL in the DPPH test, respectively. Moreover, in silico toxicity studies were conducted to predict the organ-specific toxicity through ProTox II software. The obtained results suggest the probable safety and the absence of organ-specific toxicity with all the tested samples.

IMPHY000797 derivatives have been well known for their efficacy in various diseases. Moreover, IMPHY000797 derivatives have been found to modulate such genes involved in multiple neurological disorders. Hence, this study seeks to identify such genes and the probable molecular mechanism that could be involved in the pathogenesis of Parkinson’s disease. The study utilized various biological tools such as DisGeNET, STRING, Swiss target predictor, Cytoscape, AutoDock 4.2, Schrodinger suite, ClueGo, and GUSAR. All the reported genes were obtained using DisGeNET, and further, the common genes were incorporated into the STRING to get the KEGG pathway, and all the data was converted to a protein/pathway network via Cytoscape. The clustering of the genes was performed for the gene-enriched data using two-sided hypergeometrics (p-value). The binding affinity of the IMPHY000797 was verified with the highest regulated 25 proteins via utilizing the “Monte Carlo iterated search technique” and the “ Emodel and Glide score ” function. Three thousand five hundred eighty-three genes were identified for Parkinson’s disease and 31 genes for IMPHY000797 compound, among which 25 common genes were identified. Further, the “FOXO-signaling pathway” was identified to be a modulated pathway. Among the 25 proteins, the highest modulated genes and highest binding affinity were exhibited by SIRT3, FOXO1, and PPARGC1A with the compound IMPHY000797. Further, rat toxicity analysis provided the efficacy and safety of the compound. The study was required to identify the probable molecular mechanism, which needs more confirmation from other studies, which is still a significant hit-back.

Epigallocatechin gallate (EGCG) compound (IMPHY000226) has the potential to modulate multiple molecular mechanisms involved in Parkinson’s disease. Multiple targets such as SIRT3, FOXO1, PRKAA1, PPARGC1A, and CREBBP directly regulate reactive oxygen species levels and oxidative stress, suggesting that targeting these genes could help prevent further cellular damage. EGCG targets were identified using Swiss target prediction, revealing 31 targets modulated by EGCG. Specific keywords were used to identify 4663 targets related to PD modulation. The network was constructed and analyzed using the node and edge counts. Clustering analysis identified specific target groups with high edge counts and Kappa scores, indicating potential key players in PD modulation. The targets SIRT3, FOXO1, and PPARGC1A were predicted to have the highest binding energies via dual algorithm-based molecular docking studies. The MD simulation studies were performed for the highest-docked targets, SIRT3, FOXO1, and PPARGC1A, to assess the stability and interactions. The cell viability assays were conducted at various dosage concentrations for EGCG and resveratrol, which provided dose-dependent effects on cell survival. In the toxicity-induced group, the highest % cell viability of 94% and 81% was observed at a dosage of 6.25 µg/mL and 12.5 µg/mL. The toxicity-induced gene expression studies indicated that the EGCG upregulated the targets SOD2, FOXO1, and GPx. EGCG and resveratrol upregulated the targets SOD2, FOXO1, and GPx at a dosage concentration of 12.5 µg/mL. EGCG was found to be more potent than the resveratrol molecule, indicating that EGCG can be used as an anti-Parkinson agent.

Mulberry or Morus alba fruits, belonging to the Moraceae family, are well recognized for their distinct taste and high nutritional content. Nevertheless, studies revealing the toxic effects of fruits are scanty. This study aimed to examine the adverse effects of methanolic fruit extract (MFME) derived from M. alba on mice following OECD 425 guidelines. The female Swiss albino mice were divided into two distinct categories. One group was designated as the control group (administered vehicle), while the other was assigned as the test group (administered 2000 mg/kg MFME orally). Subsequently, behavioral changes were monitored daily, and body weights, relative organ weights, and biochemical and hematological parameters were measured. Additionally, liver, kidney, heart, brain, and ovary assessments were conducted on the 14th day to detect any signs of toxicity. A histopathological investigation was conducted on the anesthetized animals’ vital organs (heart, liver, kidney, brain, and ovary). The study’s findings indicate that the oral administration of MFME did not result in any mortality. Additionally, no significant changes were seen in behavior, food and water intake, biochemical parameters, hematological investigations, and organ weights. Furthermore, the histological analysis revealed no notable pathological alterations in the separated essential organs of mice treated with MFME. The results of this study indicate that the oral administration of MFME is deemed safe up to the maximum test dosage of 2000 mg/kg.

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the synovial joints. A highly potent antagonist of C-C chemokine receptor 5 (CCR5), maraviroc (MVC), plays an essential role in treating several infectious diseases but has not yet been evaluated for its potential effects on RA development. This study focused on evaluating the therapeutic potential of MVC on collagen-induced arthritis (CIA) in DBA/1J mice. Following CIA induction, animals were treated intraperitoneally with MVC (50 mg/kg) daily from day 21 until day 35 and evaluated for clinical score and histopathological changes in arthritic inflammation. We further investigated the effect of MVC on Th9 (IL-9, IRF-4, and GATA3) and Th17 (IL-21R, IL-17A, and RORγT) cells, TNF-α, and RANTES in CD8+ T cells in the spleen using flow cytometry. We also assessed the effect of MVC on mRNA and protein levels of IL-9, IL-17A, RORγT, and GATA3 in knee tissues using RT-PCR and western blot analysis. MVC treatment in CIA mice attenuated the clinical and histological severity of inflammatory arthritis, and it substantially decreased IL-9, IRF4, IL-21R, IL-17A, RORγT, TNF-α, and RANTES production but increased GATA3 production in CD8+ T cells. We further observed that MVC treatment decreased IL-9, IL-17A, and RORγt mRNA and protein levels and increased those of GATA3. This study elucidates the capacity of MVC to ameliorate the clinical and histological signs of CIA by reducing pro-inflammatory responses, suggesting that MVC may have novel therapeutic uses in the treatment of RA.

This study explores the potential of Ailanthus excelsa Roxb. for managing obesity by evaluating its effects on key metabolic enzymes. We evaluated a hydroalcoholic extract and its fractions for their ability to modulate important metabolic enzymes, porcine pancreatic lipase , HMG-CoA reductase , α-glucosidase , and α-amylase activities. Our methodology integrated in vitro enzymatic assays with cluster analysis (MCODE, ClueGO, and Cluepedia) and network pharmacology to elucidate interactions between metabolites and target enzymes. Protein-protein interaction (PPI) analysis, consisting of a network with 51 nodes and 264 edges, was performed using the CytoNCA plugin to calculate topological parameters. Key targets were identified based on degree centrality, including ADIPOQ , PPARA , PPARG , IL6 , TNF , and AKT1 . Cluster analysis of the PPI networks, conducted using the MCODE plugin, highlighted a top cluster with a high score of 22.82. Network pharmacology has identified key targets associated with obesity, including HK1 , HK2 , PIK3CA , AKT1 , MTOR , CD36 , ACACB , SLC2A4 , CPTIA , INSR , ACACA , FASN , and ADIPOQ . These targets are linked to highly modulated metabolic pathways. Isoquercetin shows significant binding affinities: − 7.11 for HMG-CoA Reductase (PDB ID: 1HW9), -9.96 for lipase (PDB ID: 1LPB), − 8.96 for α-amylase , and − 10.41 for α-Glucosidase (PDB ID: 3A47). The ethyl acetate fractions exhibit notable inhibition of Porcine Pancreatic lipase (IC 50 : 56.25 ± 4.85 µg/mL) and HMG-CoA reductase (IC 50 : 108.27 ± 3.38 µg/mL), α-glucosidase (IC 50 : 117.08 ± 3.28 µg/mL), and α-amylase (IC 50 : 125.93 ± 2.29 µg/mL). Moreover, metabolites showed stronger binding affinities to all four enzymes than reference molecules. By integrating in vitro assays with molecular modeling , this study highlights the promising potential of A. excelsa and its fractions in obesity management, offering valuable insights into its therapeutic applications.

Filamentous Fungal Human Pathogens (FFHPs) such as Aspergillus fumigatus , are growing resistant to currently available antifungal drugs. One possible target, the Nucleoside diphosphate kinase (Ndk) is significant for nucleotide biosynthesis and crucial for fungal metabolism. Violacein, a natural food colorant, was examined for its antifungal effects against Aspergillus fumigatus via computational approach against the Ndk protein. Known and predicted interactions of Ndk with proteins was performed using the STRING application. Molecular docking was performed using Schrodinger Maestro software (V.14.1) under enhanced precision docking, with OPLS4 forcefield. MDS was performed for 500ns under OPLS4 forcefield and the TIP3P solvent system. The geometry optimization for DFT was performed using the Becke 3-parameter exchange functional (B3LYP) method. The Molecular Docking Studies revealed significant interactions with good binding energy between Violacein and Ndk. Subsequent MD Simulations confirmed the stability of Violacein-Ndk complex, compared to the reference ligand-complex, indicating a stable interaction between the protein and violacein. The energy band gap of violacein was found to be 0.072567 eV suggesting its softness with lower kinetic stability and higher chemical reactivity. The results suggest Violacein could potentially disrupt nucleotide metabolism by targeting Ndk, thus demonstrating antifungal activity. However, further experimental validation is required to confirm these computational findings and explore the practical use of Violacein in antifungal treatments.

Nutraceuticals exert a series of health benefits, including protection against cardiovascular diseases. In this study, naringin, naringenin, and quercetin were tested for their safety and efficacy in ameliorating angiotensin (Ang) II-induced cardiac hypertrophy through carbonic anhydrase II (CA-II) inhibition. In silico molecular docking and MD simulations exhibited that naringin strongly binds CA-II with a docking score of -9.55 kcal/mol and hydrogen bonding energy of -6.07 kcal/mol. Naringin formed stable hydrogen bond interactions with Asn62, Trp5, and N-acetyl His4 via catalytic water molecule, and a continuous interaction via major water bridge with N-acetyl His4, His4, and Trp5. Moreover, naringin effectively inhibited CA-II activity with an IC 50 value of 82.99 ± 4.92 nM, followed by naringenin and quercetin. Of note, all the tested nutraceuticals were found to be safe as evident from the cell viability assays. Further, naringin effectively attenuated cardiac hypertrophy, as indicated by the reductions in the Ang II-induced increases in cell surface area of H9c2 cardio myoblasts (165.6 ± 1.26% Ang II vs. 109.8 ± 1.88% Ang II + naringin), followed by naringenin and quercetin. Furthermore, naringin significantly inhibited CA-II activity (191.77 ± 7.69% Ang II vs. 120.16 ± 5.52% Ang II + naringin) and suppressed Ang II-induced CA-II and Na + /H + exchanger 1 (NHE1) protein expression. Besides, naringin suppressed Ang II-induced CA-II, NHE1, Na + /Ca 2+ exchanger 1 (NCX1), and angiotensin-converting enzyme (ACE1) mRNA expression. Collectively, naringin when compared to naringenin and quercetin effectively attenuated Ang II-induced cardio myoblast hypertrophy, CA-II activity, CA-II, and NHE1 expression. The naringin-mediated attenuation of cardiac hypertrophy might be through the inhibition of CA-II enzyme activity, and the suppression of NHE1, and NCX1.

In order to investigate for a new effective and safe anticancer drug, we synthesized a novel series of quinazoline containing biologically active substituted-sulfonamide moiety at 3- position 4a–n. The structure of the newly prepared compounds was proved by microanalysis, IR, 1H-NMR, 13C-NMR and mass spectral data. All the synthesized compounds were evaluated for their in vitro cytotoxic activity in numerous cancer cell lines including A549, HepG-2, LoVo and MCF-7 and normal HUVEC cell line. The two most active compounds 4d and 4f were then tested for their apoptosis induction using DNA content and Annexin V-FITC/PI staining. Moreover, apoptosis initiation was also confirmed using RT-PCR and Western blot. To further understand the binding preferences of quinazoline sulfonamides, docking simulations were used. Among the fourteen new synthesized compounds, we found that compounds 4d and 4f exerted the strongest cytotoxicity against MCF-7 cells with an IC50 value of 2.5 and 5 μM, respectively. Flow cytometry data revealed the ability of compounds 4d and 4f to mediate apoptosis and arrest cell cycle growth at G1 phase. Furthermore, RT-PCR and Western blot results suggested that both 4d and 4f activates apoptotic cell death pathway in MCF-7 cells. Molecular docking assessments indicated that compounds 4d and 4f fit perfectly into Bcl2’s active site. Based on the biological properties, we conclude that both compounds 4d and 4f could be used as a new type of anticancer agent, which provides a scientific basis for further research into the treatment of cancer.