• Flanagan Weeks posted an update 6 months, 1 week ago

    Pre-clinical and clinical studies evidence that the inhibition of complement components results in reduced complement deposits on target and non-target tissues, and aid in recovery from the pathological conditions of ARDS. Complement inhibitors (monoclonal antibody, protein, peptide, small molecules, etc.) exhibit great promise in blocking the activity of complement components and its downstream effects under various pathological conditions including SARS-CoV. Therefore, we hypothesize that targeting the potential complement inhibitors and complement cascade to counteract lung inflammation would be a better strategy to treat COVID-19.Advancement in nanotechnology has improved ways for large-scale production and characterization of nanoparticles of physiologically important metals. The current study explores the impact of Zinc Oxide Nanoparticles (ZnO-NP) and Chitosan-Zinc oxide nano-bioformulation (CH-ZnO) in tissue culture raised callus of Nicotiana benthamiana. Results indicated augmented biomass in CH-ZnO treated callus, while a reduced biomass was observed in ZnO-NP treated callus, at all the concentrations tested. Higher chlorophyll and carotenoid content were recorded in callus treated with 800 ppm CH-ZnO as compared to ZnO-NP treated callus. A higher accumulation of proline was observed in CH-ZnO treated callus when compared to ZnO-NP treatment, which was significantly higher at 50, 200 and 400 ppm CH-ZnO treatment. A maximum reduction in malondialdehyde (MDA) content was recorded at 800 ppm, for both the nano-formulations tested. Likewise, a significant reduction in the H2O2 levels was observed in all the treatments, while the callus treated with 400 ppm ZnO-NP and 800 ppm CH-ZnO recorded the highest reduction. Phenylalanine Ammonia-Lyase (PAL), activity increased significantly in callus treated with 400 ppm concentration for both ZnO-NP and CH-ZnO with respect to control. An increased level of tannin and nicotine were recorded in callus supplemented with 50, 200 and 400 ppm CH-ZnO. Notably, a significant decline of 94 and 52% in tannin content and 25 and 50% in nicotine content was recorded in the callus treated with 800 ppm CH-ZnO and ZnO-NP, respectively. The findings of this study suggest that an optimized dosage of these nano-bioformulations could be utilized to regulate the nicotine content and stress tolerance level.A variety of biological materials including schwertmannite, jarosite, iron-sulfur cluster (ISC) and magnetosomes can be produced by Acidithiobacillus ferrooxidans (A. DSSCrosslinker ferrooxidans). Their possible formation mechanisms involved in iron transformation, iron transport, and electron transfer were proposed. The schwertmannite formation usually occurs under the pH of 2.0-3.51, and a lower or higher pH will promote jarosite to be produced. Available Fe2+ in the environment and the carrier proteins that can transport Fe2+ to the intracellular membranes of A. ferrooxidans play a critical role in the synthesis of magnetosomes and ISC. The potential applications of these biological materials were reviewed, including removal of heavy metal by schwertmannite, detoxification of toxic species by jarosite, the transference of electron and ripening the iron sulfur protein by ISC, and biomedical application of magnetosomes. Additionally, some perspectives for the molecular mechanisms of synthesis and regulation of these biomaterials were briefly described.Different carbon sources lead to differential acarbose production in Actinoplanes. To uncover the underlying differentiation in the context of genes and pathways, we performed transcriptome sequencing of Actinoplanes utahensis ZJB-03852 grown on different saccharides, such as glucose, maltose, or the saccharide complex consisting of glucose plus maltose. The differentially expressed genes were classified into GO (gene ontology) terms and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways for functional annotations. Key enriched modules were uncovered. Our data revealed that both maltose and its complex with glucose gave improved acarbose titer. Sugar transportation, cytochrome oxidase, protein synthesis and amino acid metabolism modules were enriched under the saccharide complex condition, while ferritin metabolism gene expressions were enriched in the glucose medium. Our results provided the foundation for uncovering the mechanism of carbon source on acarbose production in A. utahensis.In this study, the aerobic activated sludge for skatole removal was enriched from pig slurry in three parallel sequencing batch reactors. The sludge system exhibited a satisfactory performance for skatole removal during the 40 days operation. High-throughput sequencing results showed that the α-diversity remained unchanged before and after the operation process. However, the structures of bacterial and fungal communities notably shifted. Particularly, Arthrobacter increased to be the major bacterial genus from 2.15 ± 0.76% (day 0) to 23.80 ± 24.36% (day 40), and Fusicolla became the major fungal genus from 1.20 ± 0.48% (day 0) to 37.17 ± 7.47% (day 40). These results indicated that Arthrobacter and Fusicolla might participate in skatole removal in sludge systems, though both genera were not reported to be able to degrade skatole. This is the first study describing skatole-degrading bacterial and fungal communities in the enrichment from pig slurry to the best of our knowledge, providing important guidance for skatole control and bioremediation.Malaria remains the leading cause of deaths globally, despite significant advancement towards understanding its epidemiology and availability of multiple therapeutic interventions. Poor efficacy of the approved vaccine, and the rapid emergence of antimalarial drug resistance, warrants an urgent need to expedite the process of development of new lead molecules targeting malaria. Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes crucial for ribosomal protein synthesis and are valid antimalarial targets. This study explores the prospects of (re-)positioning the repertoire of approved drugs and natural products as potential malarial aaRS inhibitors. Molecular docking of these two sets of small-molecules to lysyl-, prolyl-, and tyrosyl- synthetases from Plasmodium followed by a comparison of the top-ranking docked compounds against human homologs facilitated identification of promising molecular scaffolds. Raltitrexed and Cefprozil, an anticancer drug and an antibiotic, respectively, showed stronger binding to Plasmodium aaRSs compared to human homologs with > 4 kcal/mol difference in the docking scores.

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