Wheat straw is a highly promising raw material for bio-refinery strategies. Most of the literature related to lignocellulose fractionation focuses on cellulose purification and hemicellulose solubilization. Pre-treatments for hemicellulose solubilization without the formation of undesired products usually reach low extraction yields, which leaves an important hemicellulose fraction unused. In this work, we propose a mild process for the efficient extraction of the hemicellulose fraction of wheat straw assisted by partial enzymatic hydrolysis with three commercial endo-xylanase cocktails. A first step with alkali at 40 ºC helped to disrupt the lignocellulosic structure and removed 19% of lignin while maintaining most of the hemicellulose in the solid. The enzymatic step enabled reaching extraction yields of 59.8%, 51.9%, and 42.5% with Ultraflo L, Pentopan mono conc, and Shearzyme 500L, respectively. We also discuss the catalytic properties of each endo-xylanase, in particular, their adscription to the GH10 or GH11 glycosyl hydrolase family, and the relevant role of accessory enzymes.
Friday, 18 February 2022
Thursday, 17 February 2022
Integrated Machine Learning and Chemoinformatics-Based Screening of Mycotic Compounds against Kinesin Spindle ProteinEg5 for Lung Cancer Therapy
Among the various types of cancer, lung cancer is the second most-diagnosed cancer worldwide. The kinesin spindle protein, Eg5, is a vital protein behind bipolar mitotic spindle establishment and maintenance during mitosis. Eg5 has been reported to contribute to cancer cell migration and angiogenesis impairment and has no role in resting, non-dividing cells. Thus, it could be considered as a vital target against several cancers, such as renal cancer, lung cancer, urothelial carcinoma, prostate cancer, squamous cell carcinoma, etc. In recent years, fungal secondary metabolites from the Indian Himalayan Region (IHR) have been identified as an important lead source in the drug development pipeline. Therefore, the present study aims to identify potential mycotic secondary metabolites against the Eg5 protein by applying integrated machine learning, chemoinformatics based in silico-screening methods and molecular dynamic simulation targeting lung cancer. Initially, a library of 1830 mycotic secondary metabolites was screened by a predictive machine-learning model developed based on the random forest algorithm with high sensitivity (1) and an ROC area of 0.99. Further, 319 out of 1830 compounds screened with active potential by the model were evaluated for their drug-likeness properties by applying four filters simultaneously, viz., Lipinski’s rule, CMC-50 like rule, Veber rule, and Ghose filter. A total of 13 compounds passed from all the above filters were considered for molecular docking, functional group analysis, and cell line cytotoxicity prediction. Finally, four hit mycotic secondary metabolites found in fungi from the IHR were screened viz., (−)-Cochlactone-A, Phelligridin C, Sterenin E, and Cyathusal A. All compounds have efficient binding potential with Eg5, containing functional groups like aromatic rings, rings, carboxylic acid esters, and carbonyl and with cell line cytotoxicity against lung cancer cell lines, namely, MCF-7, NCI-H226, NCI-H522, A549, and NCI H187. Further, the molecular dynamics simulation study confirms the docked complex rigidity and stability by exploring root mean square deviations, root mean square fluctuations, and radius of gyration analysis from 100 ns simulation trajectories. The screened compounds could be used further to develop effective drugs against lung and other types of cancer.
Wednesday, 16 February 2022
Evaluation and Mathematical Analysis of a Four-Dimensional Lotka–Volterra-like Equation Designed to Describe the Batch Nisin Production System
Nisin, an antibacterial compound produced by Lactococcus lactis strains, has been approved by the US Food and Drug Administration to be used as a safe food additive to control the growth of undesirable pathogenic bacteria. Nisin is commonly described as a pH-dependent primary metabolite since its production depends on growth and culture pH evolution. However, the relationships between bacteriocin synthesis (BT), biomass production (X), culture pH, and the consumption of the limiting nutrient (total nitrogen: TN) have not been described until now. Therefore, this study aims to develop a competitive four-dimensional Lotka–Volterra-like Equation (predator-prey system) to describe these complex relationships in three series of batch fermentations with L. lactis CECT 539 in diluted whey (DW)-based media. The developed four-dimensional predator-prey system accurately described each individual culture, providing a good description of the relationships between pH, TN, X, and BT, higher values for R2 and F-ratios, lower values (<10%) for the mean relative percentage deviation modulus, with bias and accuracy factor values approximately equal to one. The mathematical analysis of the developed equation showed the existence of one asymptotically stable equilibrium point, and the phase’s diagram obtained did not show the closed elliptic trajectories observed in biological predator-prey systems.
Tuesday, 15 February 2022
Thermochemical Characterization of Eight Seaweed Species and Evaluation of Their Potential Use as an Alternative for Biofuel Production and Source of Bioactive Compounds
Monday, 14 February 2022
Luteolin Alleviates Epithelial-Mesenchymal Transformation Induced by Oxidative Injury in ARPE-19 Cell via Nrf2 and AKT/GSK-3β Pathway
Oxidative stress plays a critical role in age-related macular degeneration (AMD), and epithelial-mesenchymal transition (EMT) is involved in this process. The aim of this study was to investigate the protective effects of luteolin, a natural flavonoid with strong antioxidant activity, on HO-induced EMT in ARPE-19 cells. ARPE-19 cells were incubated with HO at 200 μΜ to induce oxidative stress-associated injury. Cell viability assay showed that luteolin at 20 and 40 μM significantly promoted cell survival in HO-treated ARPE-19 cells. Luteolin also markedly protected ARPE-19 cells from HO-induced apoptosis. Cell migration assay presented that luteolin significantly reduced HO-induced migration in APRE-19 cells. EMT in ARPE-19 cells was detected by western blotting and immunofluorescence. The results showed that HO significantly upregulated the expression of α-SMA and vimentin and downregulated the expression of ZO-1 and E-cadherin, while cells pretreated with luteolin showed a reversal. Meanwhile, the assessment of effects of luteolin on the Nrf2 pathway indicated that luteolin promoted Nrf2 nuclear translocation and upregulated the expressions of HO-1 and NQO-1. In addition, luteolin significantly increased the activities of SOD and GSH-PX and decreased intracellular levels of ROS and MDA in HO-treated ARPE-19 cells. Meanwhile, we observed that the expression of TGF-β2, p-AKT, and p-GSK-3β was upregulated in HO-treated ARPE-19 cells and downregulated in luteolin-treated cells, revealing that luteolin inhibited the activation of the AKT/GSK-3β pathway. However, these effects of luteolin were all annulled by transfecting ARPE-19 cells with Nrf2 siRNA. Our current data collectively indicated that inhibition of luteolin on EMT was induced by oxidative injury in ARPE-19 cell through the Nrf2 and AKT/GSK-3βpathway, suggesting that luteolin could be a potential drug for the treatment of dry AMD.
Wednesday, 2 February 2022
Effect of Silymarin as an Adjunct Therapy in Combination with Sofosbuvir and Ribavirin in Hepatitis C Patients: A Miniature Clinical Trial
Silymarin is proclaimed to be a blend of flavonolignans or phytochemicals. An era of new generation of direct-acting antivirals (DAAs) has commenced to have facet effect in swaying of the hepatitis C virus (HCV). Nonetheless, this therapy has serious side effects that jeopardize its efficacy. This study is aimed at probing the effects of ribavirin (RBV) and sofosbuvir (SOF) along with silymarin as an adjunct therapy on hematological parameters and markers of obscured oxidative stress. The effect of DAAs along with silymarin was also examined on variable sex hormone level and liver function markers such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin. The study was followed to determine viral load and viral genotypes. A total of 30 patients were randomly divided into two equal groups comprising the control group () and treatment group (). The control group was solely administered with DAAs (SOF and RBV; 400 mg/800 mg each/day). Conversely, the treatment group was dispensed with DAAs, but with adjunct therapy of silymarin (400 mg/day) along with DAAs (400/800 mg/day) over period of 8 weeks. Sampling of blood was performed at pre- and posttreatment levels for the evaluation of different propound parameters. Our data showed that silymarin adjunct therapy enhances the efficiency of DAAs. A decrease in menace level of liver markers such as ALT, ALP, AST, and bilirubin was observed (). The adjunct therapy concurrently also demonstrated an ameliorative effect on hematological indices and oxidative markers, for instance, SOD, TAS, GSH, GSSG, and MDA (), diminishing latent viral load. The silymarin administration was also found to revamp the fluster level of sex hormones. Our outcomes provide evidence that systematic administration of silymarin effectively remits deviant levels of hematological, serological, hormonal, and antioxidant markers. This demonstrates a possibly unique role of silymarin in mitigating hepatitis C.