Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain.

Manganese neurotoxicity has been reported to cause a neurodegenerative disease known as parkinsonism. Previous reports have shown that the expression of the KH-type splicing regulatory protein (KHSRP), a nucleic acid-binding protein, and NLRP3 is increased upon Mn exposure. However, the relation between these two during Mn toxicity has not been fully deduced. The mouse neuroblastoma (N2a) and SD rats are treated with LPS and MnCl2 to evaluate the expression of KHSRP and NLRP3. Further, the effect of the NLRP3 inhibitor MCC950 is checked on the expression of NLRP3, KHSRP and pro-inflammatory markers (TNFα, IL-18 and IL-1ß) as well as the caspase-1 enzyme. Our results demonstrated an increment in NLRP3 and KHSRP expression post-MnCl2 exposure in N2a cells and rat brain, while on the other hand with LPS exposure only NLRP3 expression levels were elevated and KHSRP was found to be unaffected. An increased expression of KHSRP, NLRP3, pro-inflammatory markers and the caspase-1 enzyme was observed to be inhibited with MCC950 treatment in MnCl2-exposed cells and rats. Manganese exposure induces NLRP3 and KHSRP expression to induce neuroinflammation, suggesting a correlation between both which functions in toxicity-related pathways. Furthermore, MCC950 treatment reversed the role of KHSRP from anti-inflammatory to pro-inflammatory.

In Silico Molecular Docking and Simulation Studies of Protein HBx Involved in the Pathogenesis of Hepatitis B Virus-HBV.

Current drug discovery involves finding leading drug candidates for further development. New scientific approaches include molecular docking, ADMET studies, and molecular dynamic simulation to determine targets and lead compounds. Hepatitis B is a disease of concern that is a life-threatening liver infection. The protein considered for the study was HBx. The hepatitis B X-interacting protein crystal structure was obtained from the PDB database (PDB ID-3MSH). Twenty ligands were chosen from the PubChem database for further in silico studies. The present study focused on in silico molecular docking studies using iGEMDOCK. The triethylene glycol monoethyl ether derivative showed an optimum binding affinity with the molecular target HBx, with a high negative affinity binding energy of -59.02 kcal/mol. Lipinski's rule of five, Veber, and Ghose were followed in subsequent ADMET studies. Molecular dynamic simulation was performed to confirm the docking studies and to analyze the stability of the structure. In these respects, the triethylene glycol monoethyl ether derivative may be a promising molecule to prepare future hepatitis B drug candidates. Substantial research effort to find a promising drug for hepatitis B is warranted in the future.

Characterization of Bioactive Compounds from Acacia concinna and Citrus limon, Silver Nanoparticles' Production by A. concinna Extract, and Their Biological Properties.

The applications of bioactive compounds from medicinal plants as therapeutic drugs are largely increasing. The present study selected the bioactive compounds from Acacia concinna (A. concinna) and Citrus limon (C. limon) to assess their phytochemicals, proteins, and biological activity. The plant material was collected, and extraction performed as per the standard procedure. Qualitative analysis was undertaken, and identification of functional organic groups was performed by FTIR and HPLC. Antibacterial, anticancer, antioxidant, antihyperglycemic, antihyperlipidemic, and inhibition kinetics studies for enzymes were performed to assess the different biological activities. Flavonoids and phenols were present in a significant amount in both the selected plants. A. concinna showed significant antimicrobial activity against Z. mobilis, E. coli, and S. aureus, with minimum inhibition zones (MIZ) of 24, 22, and 20 mm, respectively. C. limon strongly inhibited all the tested pathogenic bacteria with maximum and minimum MIZ of 32 and 17 mm. A. concinna silver nanoparticles also exhibited potent antimicrobial activity. Both extracts showed substantial antioxidant, antihyperlipidemic, antidiabetic, anticancer (MCF-7), and anti-urease (antiulcer) properties. To conclude, these plants can be used to treat hyperlipidemia, diabetes, cancer, and gastrointestinal ulcers. They can also serve as antimicrobial and antioxidant agents. Thus, the studied plants must be exploited cost-effectively to generate therapeutic drugs for various diseases.

Plant-Based Synthesis of Gold Nanoparticles and Theranostic Applications: A Review.

Bionanotechnology is a branch of science that has revolutionized modern science and technology. Nanomaterials, especially noble metals, have attracted researchers due to their size and application in different branches of sciences that benefit humanity. Metal nanoparticles can be synthesized using green methods, which are good for the environment, economically viable, and facilitate synthesis. Due to their size and form, gold nanoparticles have become significant. Plant materials are of particular interest in the synthesis and manufacture of theranostic gold nanoparticles (NPs), which have been generated using various materials. On the other hand, chemically produced nanoparticles have several drawbacks in terms of cost, toxicity, and effectiveness. A plant-mediated integration of metallic nanoparticles has been developed in the field of nanotechnology to overcome the drawbacks of traditional synthesis, such as physical and synthetic strategies. Nanomaterials' tunable features make them sophisticated tools in the biomedical platform, especially for developing new diagnostics and therapeutics for malignancy, neurodegenerative, and other chronic disorders. Therefore, this review outlines the theranostic approach, the different plant materials utilized in theranostic applications, and future directions based on current breakthroughs in these fields.

Molecular modelling and simulation techniques to investigate the effects of fungal metabolites on the SARS-CoV-2 RdRp protein inhibition.

Various protein/receptor targets have been discovered through in-silico research. They are expanding rapidly due to their extensive advantage of delivering new drug candidates more quickly, efficiently, and at a lower cost. The automation of organic synthesis and biochemical screening will lead to a revolution in the entire research arena in drug discovery. In this research article, a few fungal metabolites were examined through an in-silico approach which involves major steps such as (a) Molecular Docking Analysis, (b) Drug likeness and ADMET studies, and (c) Molecular Dynamics Simulation. Fungal metabolites were taken from Antibiotic Database which showed antiviral effects on severe viral diseases such as HIV. Docking, Lipinski's, and ADMET analyses investigated the binding affinity and toxicity of five metabolites: Chromophilone I, iso; F13459; Stachyflin, acetyl; A-108836; Integracide A (A-108835). Chromophilone I, iso was subjected to additional analysis, including a 50 ns MD simulation of the protein to assess the occurring alterations. This molecule's docking data shows that it had the highest binding affinity. ADMET research revealed that the ligand might be employed as an oral medication. MD simulation revealed that the ligand-protein interaction was stable. Finally, this ligand can be exploited to develop SARS-CoV-2 therapeutic options. Fungal metabolites that have been studied could be a potential source for future lead candidates. Further study of these molecules may result in creating an antiviral drug to battle the SARS-CoV-2 virus.