Progression-free survival estimation of docetaxel-based second-line treatment for advanced non-small cell lung cancer: a pooled analysis from 18 randomized control trials.

Background: Lung cancer is the foremost cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) accounting for 85-90% of cases. Targeted therapy is the most essential therapeutic option for NSCLC, other common treatments include radiation therapy, surgery, chemotherapy, and immunotherapy. Objective: Our study objective was to estimate whether progression-free survival (PFS) is an outcome of NSCLC extracted from 18 randomized control trials (RCTs) with docetaxel as experimental group and antineoplastic agent, kinase inhibitor, and monoclonal antibodies as a control group. Methods: We selected relevant studies published between 2011 and 2022 using Google Scholar, PubMed, Scopus, Science Direct, and Cochrane Library. Advanced NSCLC, chemotherapy, RCT, docetaxel, and second-line treatment were the terms included in the search. A total of 9738 patients were evaluated from the 18 identified studies. We used the meta package of R Studio to perform the meta-analysis. Graphical funnel plots were used to evaluate publication bias visually. Results: Patients who underwent docetaxel-based therapy had a considerably longer PFS than those who got antineoplastic agents, kinase inhibitors, or monoclonal antibodies-based treatment. Patients in the standard treatment arm had a slightly longer PFS than those in the experimental therapy arm in the overall meta-analysis. Conclusion: Docetaxel outperformed monoclonal antibodies, antineoplastic agents, and kinase inhibitors in the second-line therapy of advanced NSCLC since PFS was extensively utilized.

Evaluating the Antimicrobial and Anti-Hemolytic Activity of Synthesized Pseudopeptide against Leptospiral Species: In Silico and In Vitro Approach.

Bacterial infections are one of the leading causes of morbidity, mortality, and healthcare complications in patients. Leptospirosis is found to be the most prevalent, re-emergent, and neglected tropical zoonotic disease worldwide. The adaptation to various environmental conditions has made Leptospira acquire a large genome (~4.6 Mb) and a complex outer membrane, making it unique among bacteria that mimic the symptoms of jaundice and hemorrhage. Sph2 is another important virulence factor that enhances hemolytic sphingomyelinase-capable of moving inside mitochondria-which increases the ROS level and decreases the mitochondrial membrane potential, thereby leading to cell apoptosis. In the present study, 25 suspected bovine serum samples were subjected to the Microscopic Agglutination Test (MAT) across the Mysuru region. Different samples, such as urine, serum, and aborted materials from the confirmed MAT-positive animals, were used for isolation and genomic detection by conventional PCR targeting virulence gene, Lipl32, using specific primers. Further, in vitro and in silico studies were performed on isolated cultures to assess the anti-leptospiral, anti-hemolytic, and sphingomyelinase enzyme inhibition using novel pseudopeptides. The microdilution technique (MDT) and dark field microscope (DFM) assays revealed that at a concentration of 62.5 µg/mL, the pseudopeptide inhibited 100% of the growth of Leptospira spp., suggesting its efficiency in the treatment of leptospirosis. The flow cytometry analyses show the potency of the pseudopeptide against sphingomyelinase enzymes using human umbilical vein endothelial cells (HUVECs). Thus, the present study demonstrated the efficacy of the pseudopeptide in the inhibition of the growth of Leptospira, and therefore, this can be used as an alternative drug for the treatment of leptospirosis.

Evaluation of codon usage patterns and molecular evolution dynamics in Japanese encephalitis virus: An integrated bioinformatics approach.

In the recent survey, Japanese encephalitis (JE) is one of the most common mosquito-borne diseases, accounting for ∼30% of fatalities. The outbreaks of the JE virus (JEV) suggests that exhaustive study is essential for the prevention and management of the disease. The disease mainly spreads in humans and pigs by the vector: mosquito; as this is a major concern, this study had employed various bioinformatics tools to investigate the codon usage bias, evolutionary inference and selection pressure analysis of the Japanese encephalitis virus disease. The results indicated that the JE virus was biased and natural selection was the main factor shaping the codon usage that was determined and confirmed with the Nc, neutrality, PR2 plots and correlation analysis. The evolutionary analysis revealed that the virus had a substitution rate of 1.54 × 10-4 substitution/site/year and the tMRCA was found to be in 1723. The transmission of the virus in the map found transmissions mostly from China and transmitted across Asia and Africa. The selection pressure analysis employed three methods which had 969th codon site as diversifying site and had many purifying sites that shows the virus had evolved rapidly. The inferences from this study would aid people to employ this methodology on various diseases and also perform insilico studies in the field of vaccinology and immunoinformatics.

Plants and endophytes - a partnership for the coumarin production through the microbial systems.

Plant-based secondary metabolite production system is well established. However, host-endophyte interaction in the production of secondary metabolite is a new less exploited area that is overcoming barriers and evolving as one of the prospective fields. Endophytes such as bacteria or fungi have the ability to produce some of the secondary metabolites that mimic the plant metabolites therefore escaping the host defence system. Coumarin is one such metabolite with immense biological functions. Most of the studies have demonstrated coumarin production from fungal endophytes but not bacterial endophytes. Herein, we present an overview of all the coumarin derivatives produced from endophytic sources and their biosynthetic pathways. Furthermore, the review also throws light on the isolation of these coumarins and different derivatives with respect to their biological activity. The biotransformation of coumarin derivatives by the action of endophytic fungi is also elaborated. The present review provides an insight on the challenges faced in the coumarin production through fungal endophytes.

Prevalence of Japanese encephalitis (JE) virus in mosquitoes and animals of the Asian continent: A systematic review and meta-analysis.

BACKGROUND: Japanese encephalitis (JE) is a viral zoonotic disease that has been found in several countries of Asia and is responsible for high mortality and morbidity of men and animals in rural and sub-urban endemic areas due to the virus re-circulation among diverse hosts and vectors. The present study estimates the prevalence of the JE virus in the vector and animal population of the Asian continent using a systematic review and meta-analysis. METHODS: The Cochran collaborators' Preferred Reporting Items for Systematic Reviews and Meta-Analysis [PRISMA] guidelines were used for systematic review and meta-analysis. The heterogeneity was observed in meta-regression analysis due to several factors including region, species, and different diagnostic assays used in various studies. Thus we did sensitivity and subgroup analysis. RESULTS: The prevalence of the JE virus was calculated using a total sample size of 47,391. Subgroup analysis revealed the JE virus prevalence of 39% in the Southeast Asia region, followed by East Asia with 35% and South Asia with 15% prevalence. Hence, the overall pooled prevalence of the JE virus was 26% in the Asian continent. CONCLUSIONS: The highest proportion of infection was found in pigs amongst all animals, reinforcing the fact that they can be used as sentinels to predict outbreaks in humans. The findings of this study will enable researchers and policymakers in better understanding the disease's spatial and temporal distribution, as well as in creating and implementing location-specific JE prevention and control measures.

An insight into reactivity and bioactivity properties of quorum sensing peptides against PDE10A: a computational peptidology approach.

Peptides are currently the most promising lead molecules. Quorum sensing peptides have a variety of structural features and are regularly exposed to post-translational modifications. Antiparkinsonian drugs lose their efficacy after a long period of use, and patients develop motor problems such as drug-induced dyskinesia (DIDs). The interaction between PDE10A and cAMP is necessary for dopamine neurotransmission and may play a role in Parkinson's disease pathogenesis. cAMP and cGMP are cyclic nucleotides that act as secondary messengers in the signal transduction pathway, influencing a range of CNS activities. PDE enzymes hydrolyze phosphodiester bonds to break down cAMP and cGMP, allowing them to control intracellular levels of these second messengers effectively. PDE expression, and hence cyclic nucleotide levels and their downstream targets, may change with age and in numerous age-related illnesses, including Parkinson's disease, according to mounting evidence. At the peak of dyskinesias, cyclic nucleotide levels were lower, and using phosphodiesterase inhibitors before antiparkinsonian medicines reduced the severity of dyskinesias. In a recent study, PapRIV was found to have the ability to activate BV-2 microglia cells, indicating that this quorum sensing peptide may play a role in gut-brain contact. As a result of the current in silico work, mainly focused on QSPs as a lead molecule for inhibiting PDE10A, the SRNAT QSP sequence has been a potent molecule in molecular docking and molecular dynamics simulations. Furthermore, we can test the efficiency of therapeutic components in vitro and in vivo utilizing this computational approach against PDE10A.

Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy.

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of -8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.