Green synthesized silver nanoparticles of Terminalia bellirica leaves extract: synthesis, characterization, in-silico studies, and antimalarial activity.

Malaria is a mosquito-borne infectious disease that is caused by the Plasmodium parasite. Most of the available medication are losing their efficacy. Therefore, it is crucial to create fresh leads to combat malaria. Green silver nanoparticles (AgNPs) have recently attracted a lot of attention in biomedical research. As a result, green mediated AgNPs from leaves of Terminalia bellirica, a medicinal plant with purported antimalarial effects, were used in this investigation. Initially, cysteine-rich proteins from Plasmodium species were studied in silico as potential therapeutic targets. With docking scores between -9.93 and -11.25 kcal/mol, four leaf constituents of Terminalia bellirica were identified. The green mediated silver nanoparticles were afterward produced using leaf extract and were further examined using UV-vis spectrophotometer, DLS, Zeta potential, FTIR, XRD, and FESEM. The size of synthesized TBL-AgNPs was validated by the FESEM results; the average size of TBL-AgNPs was around 44.05 nm. The zeta potential study also supported green mediated AgNPs stability. Additionally, Plasmodium falciparum (3D7) cultures were used to assess the antimalarial efficacy, and green mediated AgNPs could effectively inhibit the parasitized red blood cells (pRBCs). In conclusion, this novel class of AgNPs may be used as a potential therapeutic replacement for the treatment of malaria.

Identification of potential therapeutic targets for COVID-19 through a structural-based similarity approach between SARS-CoV-2 and its human host proteins.

Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host-virus protein-protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection. Objective: This study aims to identify therapeutic target proteins in humans that could act as virus-host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors. Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 ("hCoV-2"), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient's mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein. Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein. Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention.

Role of Fork-Head Box Genes in Breast Cancer: From Drug Resistance to Therapeutic Targets.

Breast cancer has been acknowledged as one of the most notorious cancers, responsible for millions of deaths around the globe. Understanding the various factors, genetic mutations, comprehensive pathways, etc., that are involved in the development of breast cancer and how these affect the development of the disease is very important for improving and revitalizing the treatment of this global health issue. The forkhead-box gene family, comprising 19 subfamilies, is known to have a significant impact on the growth and progression of this cancer. The article looks into the various forkhead genes and how they play a role in different types of cancer. It also covers their impact on cancer drug resistance, interaction with microRNAs, explores their potential as targets for drug therapies, and their association with stem cells.

Inhibition of Autophagy and the Cytoprotective Role of Smac Mimetic against ROS-Induced Cancer: A Potential Therapeutic Strategy in Relapse and Chemoresistance Cases in Breast Cancer.

With more than a million deaths each year, breast cancer is the top cause of death in women. Around 70% of breast cancers are hormonally responsive. Although several therapeutic options exist, cancer resistance and recurrence render them inefficient and insufficient. The major key reason behind this is the failure in the regulation of the cell death mechanism. In addition, ROS was also found to play a major role in this problem. The therapeutic benefits of Smac mimetic compound (SMC) BV6 on MCF7 were examined in the current study. Treatment with BV6 reduces viability and induces apoptosis in MCF7 breast cancer cells. BV6 suppresses autophagy and has demonstrated a defensive role in cancer cells against oxidative stress caused by H2O2. Overall, the present investigation shows that SMC has therapeutic and cytoprotective potential against oxidative stress in cancer cells. These Smac mimetic compounds may be used as anti-cancer drugs as well as antioxidants alone or in conjunction with other commonly used antioxidants.

Investigating the role of Kinesin family in lung adenocarcinoma via integrated bioinformatics approach.

Lung cancer is the leading cause of mortality from cancer worldwide. Lung adenocarcinoma (LUAD) is a type of non-small cell lung cancer (NSCLC) with highest prevalence. Kinesins a class of motor proteins are shown to be involved in carcinogenesis. We conducted expression, stage plot and survival analyses on kinesin superfamily (KIF) and scrutinized the key prognostic kinesins. Genomic alterations of these kinesins were studied thereafter via cBioPortal. A protein-protein interaction network (PPIN) of selected kinesins and 50 closest altering genes was constructed followed by gene ontology (GO) term and pathway enrichment analyses. Multivariate survival analysis based on CpG methylation of selected kinesins was performed. Lastly, we conducted tumor immune infiltration analysis. Our results found KIF11/15/18B/20A/2C/4A/C1 to be significantly upregulated and correlated with poor survival in LUAD patients. These genes also showed to be highly associated with cell cycle. Out of our seven selected kinesins, KIFC1 showed the highest genomic alteration with highest number of CpG methylation. Also, CpG island (CGI) cg24827036 was discovered to be linked to LUAD prognosis. Therefore, we deduced that reducing the expression of KIFC1 could be a feasible treatment strategy and that it can be a wonderful individual prognostic biomarker. CGI cg24827036 can also be used as a therapy site in addition to being a great prognostic biomarker.

Malaria therapeutics: are we close enough?

Malaria is a vector-borne parasitic disease caused by the apicomplexan protozoan parasite Plasmodium. Malaria is a significant health problem and the leading cause of socioeconomic losses in developing countries. WHO approved several antimalarials in the last 2 decades, but the growing resistance against the available drugs has worsened the scenario. Drug resistance and diversity among Plasmodium strains hinder the path of eradicating malaria leading to the use of new technologies and strategies to develop effective vaccines and drugs. A timely and accurate diagnosis is crucial for any disease, including malaria. The available diagnostic methods for malaria include microscopy, RDT, PCR, and non-invasive diagnosis. Recently, there have been several developments in detecting malaria, with improvements leading to achieving an accurate, quick, cost-effective, and non-invasive diagnostic tool for malaria. Several vaccine candidates with new methods and antigens are under investigation and moving forward to be considered for clinical trials. This article concisely reviews basic malaria biology, the parasite's life cycle, approved drugs, vaccine candidates, and available diagnostic approaches. It emphasizes new avenues of therapeutics for malaria.

An Update on the Therapeutic Anticancer Potential of Ocimum sanctum L.: "Elixir of Life".

In most cases, cancer develops due to abnormal cell growth and subsequent tumour formation. Due to significant constraints with current treatments, natural compounds are being explored as potential alternatives. There are now around 30 natural compounds under clinical trials for the treatment of cancer. Tulsi, or Holy Basil, of the genus Ocimum, is one of the most widely available and cost-effective medicinal plants. In India, the tulsi plant has deep religious and medicinal significance. Tulsi essential oil contains a valuable source of bioactive compounds, such as camphor, eucalyptol, eugenol, alpha-bisabolene, beta-bisabolene, and beta-caryophyllene. These compounds are proposed to be responsible for the antimicrobial properties of the leaf extracts. The anticancer effects of tulsi (Ocimum sanctum L.) have earned it the title of "queen of herbs" and "Elixir of Life" in Ayurvedic treatment. Tulsi leaves, which have high concentrations of eugenol, have been shown to have anticancer properties. In a various cancers, eugenol exerts its antitumour effects through a number of different mechanisms. In light of this, the current review focuses on the anticancer benefits of tulsi and its primary phytoconstituent, eugenol, as apotential therapeutic agent against a wide range of cancer types. In recent years, tulsi has gained popularity due to its anticancer properties. In ongoing clinical trials, a number of tulsi plant compounds are being evaluated for their potential anticancer effects. This article discusses anticancer, chemopreventive, and antioxidant effects of tulsi.

Identifying Isoononin and Candidissiol as Rho-associated protein kinase 1 (ROCK1) inhibitors: a combined virtual screening and MD simulation approach.

Rho-associated protein kinase 1 (ROCK1) is a member of the AGC family which plays crucial roles in inflammatory diseases and cancer progression. Elevated expression of ROCK1 has been reported in multiple cancer types, and thus it has emerged as a potential drug target for cancer therapeutics. In this study, we performed a structure-based virtual screening of the natural compounds taken from the IMPPAT database to find some potential molecules as inhibitors of ROCK1. For the first step, we selected the compounds based on the Lipinski rule of five, and then we filtered them based on their ADMET properties and PAINS value. After this, other parameters like binding affinities, docking score, biological properties and selectivity were calculated to find appropriate hits against ROCK1. Finally, we identified two natural compounds, Isoononin and Candidissiol, with appreciable binding affinity and selectivity towards ROCK1. Furthermore, all-atom molecular dynamics simulations were carried out on ROCK1 with the elucidated compounds, which suggested stability throughout the simulated trajectories of 100 ns. Taken together, Isoononin and Candidissiol could be considered as potential inhibitors of ROCK1 for developing anticancer therapeutics.Communicated by Ramaswamy H. Sarma.