In the current study the assessment of the antimicrobial and phytochemical properties of Cassia fistula, Musa paradisiaca, Ficus religiosa and Murraya koenigii plants extracts was carried out. The antibacterial potential of these plants extracts was tested against S. aureus and E. coli. The Cassia fistula and Ficus religiosa leaves showed the larger zone of inhibition in aqueous and butanolic extract respectively against Escherichia coli. Musa paradisiaca and Murraya koenigii leaves showed larger zone of inhibition in ethanolic extract against S. aureus. Qualitative phytochemical analysis showed the presence of alkaloids, flavonoids, phenols, terpenoids, steroids, glycosides, saponins, carbohydrates, proteins and tannins in all extracts while phylobatannins, emodins, anthocyanins and leucoanthocyanins were not present in these extracts. Quantitative phytochemical analysis showed the highest alkaloid content in the Murraya koenigii leaves. Highest tannin content and flavonoid content was found in Ficus religiosa leaves, while highest phenolic content was found in case of Cassia fistula. In addition to this antioxidant potential of all the extracts was determined. Musa paradisiaca leaves showed highest antioxidant potential as compared to other plant extracts. In silico analysis of bioactive components present in plant extracts was performed by molecular docking. The rutin and Glu from Musa paradisiaca and Murraya koenigii respectively, were docked with Glycogen Synthase Kinase 3 beta (1GSK-3beta) protein. Quercetin and rutin from Cassia fistula and Ficus religiosa respectively, were docked with C- reactive protein (CRP). The tested bioactive compounds showed good binding affinity with significant number of hydrogen bonds and can be used as a good alternative of synthetic drugs to treat rheumatism and wounds.

Cellulases involved in the hydrolysis of cellulose and plays a vital role in different industries like textile, detergent paper and Feed industry. Cellulases have been a prospective target for research by both the academic and industrial sectors because of the intricacy of the enzyme system and the enormous industrial potential. In the present work Thermomyces dupontii, which had previously been isolated and recorded as a promising cellulase producer were used. Both endoglucanases and betaglucosidases were purified to its homogeneity by ammonium sulfate followed by anion exchange and gel filtration chromatography. The recovery and purification fold for endoglucanases and betaglucosidases were 13.7, 10.7 % and 5.9, 2.7, respectively. The molecular weight of endoglucanases and betaglucosidases were estimated as 37 and 66 kDa on SDS-PAGE. Upon kinetic analysis the purified endoglucanases and betaglucosidases showed Km 0.63; 28.56 mg/ml and Vmax 82; 80 U/ml/min, respectively. Characterization revealed that enzyme was found to be acidophilic cellulase having optimal pH of 5.5 and 70 ⁰C. Furthermore, cellulases were accelerated in the presence of Ca²⁺ and EDTA. The cellulases had activation energy (Ea) of −44.55; −50.02 kJ/mol for carboxy-methyl-cellulose hydrolysis and Enthalpy (ΔH) 42.20; 47.70 kJ/mol and entropy ΔS −5.1 and −5.7 kJ/mol for EG and BGL, respectively. In addition to this the enzyme had a secondary structure of protein as represented by FTIR spectrum The current study suggested that purified cellulases can be used as a detergent additive to improve washing. Furthermore, it shows the biostoning ability when applied on jean fabric.

Different fungal strains were isolated from the local soil, fruits and vegetables on the basis of pectin hydrolysis. All the isolated strains were identified through microscopic studies and screened for pectinase production using solid state fermentation. The fungal strain identified as Aspergillus niger IBT-7 showed the highest pectinase production. The selected strain was further subjected to optimization through different physical and nutritional parameters to enhance the production of pectinase. Amongst seven different media tested M1 containing rice bran, moistened with Czapek’s nutrient medium showed the highest pectinase production. During optimization maximum pectinase production was achieved after 72 hrs of incubation at 30 ml of moisture content, pH 5.0 and 30°C. Xylose (1.5%) and yeast extract (1%) proved to be best supplemented carbon and nitrogen sources, respectively which gave the highest pectinase production (39.1 U/ml/min).

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key targets for atherosclerosis drug development as its binding with low-density lipoprotein receptor leads to atherosclerosis. The protein-ligand interaction helps to understand the actual mechanism for the pharmacological action. This research aims to discover the best inhibitory candidates targeting PCSK9. To start with, reported ACE inhibitors were incorporated into pharmacophore designing using PharmaGist to produce pharmacophore models. Selected models were later screened against the ZINC database using ZINCPHARMER to define potential drug candidates that were docked with the target protein to understand their interactions. Molecular docking revealed the top 10 drug candidates against PCSK9, with binding energies ranging from -9.8 kcal·mol^-1to -8.2 kcal·mol^-1, which were analyzed for their pharmacokinetic properties and oral bioavailability. Some compounds were identified as plant-derived compounds like (S)-canadine, hesperetin or labetalol (an antihypertensive drug). Molecular dynamics results showed that these substances formed stable protein-ligand complexes. (S)-canadine-PCSK9 complex was the most stable with the lowest RMSD. It was concluded that (S)-canadine may act as a potential inhibitor against atherosclerosis for the development of new PCSK9 inhibitory drugs in futurein vitroresearch.

Background: The prevalence of the chronic metabolic disorder Type 2 diabetes mellitus (T2DM) is increasing steadily, and has even turned into an epidemic in some countries. T2DM results from defective responses to insulin and obesity is a major factor behind insulin resistance in T2DM. Insulin receptor substrate (IRS) proteins are adaptor proteins in the insulin receptor signalling pathway. The insulin signalling is controlled through tyrosine phosphorylation of IRS-1 and IRS-2, and dysregulation of IRS proteins signalling may lead to glucose intolerance and eventually insulin resistance.Objective: In this work, we suggest that both glycosylation (O-GlcNAc modification) and phosphorylation of IRS-1 and -2 are involved in the pathogenesis of T2DM.Methods: Phosphorylation and O-GlcNAc modifications (Ser1101 in IRS-1 and Ser1149 in IRS-2) proteins were determined experimentally by sandwich ELISA with specific antibodies and with bioinformatics tools.Results: When IRS-1 (on Ser1101) and IRS-2 (Ser1149) become glycosylated following an increase in UDP-GlcNAc pools, it may contribute to insulin resistance. Whereas when the same (IRS-1 on Ser1101 and IRS-2 on Ser1149) are phosphorylated, the insulin signalling is inhibited.Discussion: In this work OGlcNAc-modified proteins were specifically detected using O-Glc- NAc-specific antibodies, suggesting that elevated levels of O-GlcNAc-modified proteins are found, independently of their possible involvement in Advanced Glycation End products (AGEs).Conclusion: This study suggests a mechanism, which is controlled by posttranslational modifications, and may contribute to the pathogenesis of type II diabetes.

In this study, thermophilic pectinase-producing strains were isolated. Among all the isolates, strain No. 4 was identified as Aspergillus fumigatus BT-4 based on its morphology and 18 S rDNA analysis. This strain was employed to screen various fermentation media to enhance pectinase production. Pectinases are crucial enzymes with significant industrial applications, particularly in the food and textile industries. Identifying efficient pectinase producers and optimizing their production processes are essential for improving industrial applications. Maximum pectinase production was observed using 1% grapefruit peel in M5 media. Shake flask kinetics demonstrated the highest values of specific rate constant (qp), specific growth rate (µ), product yield coefficient (Yp/x), volumetric rate of product formation (Qp), and biomass formation (Qx) after 72 h of incubation. Furthermore, Optimization of fermentation components via Response Surface Methodology (RSM) improved pectinase production by 50%, showcasing the effectiveness of factorial and central composite designs in fine-tuning parameters. The use of agricultural waste (grapefruit peel) significantly reduced production costs, offering an economically viable substrate alternative. The pectinase enzyme was purified through ammonium sulfate precipitation, gel filtration, and ion-exchange chromatography, resulting in a 2.3-fold purification. The molecular weight of the purified enzyme was determined to be 48 kDa. Enzyme kinetics, determined using a Lineweaver-Burk plot at various pectin concentrations, showed a Vmax of 32.7 UmL− 1 and a Km of 0.3 mg mL− 1. Thermodynamic parameters, including activation energy (Ea), enthalpy (ΔH), and entropy (ΔS), were measured at 41.74 kJmol− 1, 39.53 kJmol− 1, and 46.9 kJmol− 1, respectively. The study successfully isolated and identified Aspergillus fumigatus BT-4 as a potent thermophilic pectinase producer. Optimization of the fermentation process using 1% grapefruit peel in M5 media significantly enhanced pectinase production. Using grapefruit peel as an agricultural waste in pectinase production reduces costs by eliminating the need for expensive raw materials and utilizing a low-cost, sustainable, and locally available substrate. This approach also minimizes waste disposal expenses, making the process more economical. The enzyme was effectively purified, and its kinetic and thermodynamic properties were thoroughly characterized, revealing its potential for industrial applications. The comprehensive analysis of production kinetics and optimization strategies provides a robust foundation for scaling up pectinase production, contributing to more efficient and cost-effective industrial processes.