Molecular docking analysis of acetylcholinesterase inhibitors for Alzheimer's disease management.

Alzheimer's disease (AD) is a neurological disease that is related to aging and is the leading cause of dementia globally. AD has a significant influence on cognitive functions, particularly memory, resulting in a variety of functional deficits. Given the increasing prevalence of AD, there is an urgent need for the development of effective therapeutic therapies. In a quest to uncover a holistic remedy for AD, a total of 41 bioactive compounds derived from three distinct medicinal plant sources were screened to evaluate their potential to inhibit the active sites of acetylcholinesterase (AChE). The insilico screening protocol included 24 licorice-derived compounds, 5 ginkgo biloba-derived compounds, and 11 ginseng-derived compounds. Two compounds (Ginkgolide A and Licorice glycoside D2) were observed to display greater binding energy (BE) relative to the control by interacting with crucial residues in the active site of AChE. Ginkgolide A and Licorice glycoside D2 exhibited BEs of -11.3 and -11.2 kcal/mol, respectively, whereas the control, Donepezil, demonstrated a BE of -10.8 kcal/mol. Further, these compounds exhibit favorable drug-likeness properties. This study suggests that further experimental investigations can be conducted on Ginkgolide A and Licorice glycoside D2 to explore their potential therapeutic applications for AD.

Unveiling the multitargeted potency of Sodium Danshensu against cervical cancer: a multitargeted docking-based, structural fingerprinting and molecular dynamics simulation study.

Cervical Cancer (CC) is one of the most common types of cancer in women worldwide, with a significant number of deaths reported yearly. Despite the various treatment options available, the high mortality rate associated with CC highlights the need to develop new and effective therapeutic agents. In this study, we have screened the complete prepared FDA library against the Mitotic kinesin-like protein 1, Cyclin B1, DNA polymerase, and MCM10-ID using three glide-based molecular docking algorithms: HTVS, SP and XP to produce a robust calculation. All four proteins are crucial proteins that actively participate in CC development, and inhibiting them together can be a game-changer step for multitargeted drug designing. Our multitargeted screening identified Sodium (Na) Danshensu, a natural FDA-approved phenolic compound of caffeic acid derivatives isolated from Salvia miltiorrhiza. The docking score ranges from -5.892 to -13.103 Kcal/mol, and the screening study was evaluated with the pharmacokinetics and interaction fingerprinting to identify the pattern of interactions that revealed that the compound has bound to the best site it can be fitted to where maximum bonds were created to make the complex stable. The molecular dynamics simulations for 100 ns were then extended to validate the stability of the protein-ligand complexes. The results provide insight into the repurposing, and Na-danshensu exhibited strong binding affinity and stable complex formation with the target proteins, indicating its potential as a multitargeted drug against CC.Communicated by Ramaswamy H. Sarma.

Functional annotation of rhizospheric phageome of the wild plant species Moringa oleifera.

Introduction: The study aims to describe phageome of soil rhizosphere of M.oleifera in terms of the genes encoding CAZymes and other KEGG enzymes. Methods: Genes of the rhizospheric virome of the wild plant species Moringa oleifera were investigated for their ability to encode useful CAZymes and other KEGG (Kyoto Encyclopedia of Genes and Genomes) enzymes and to resist antibiotic resistance genes (ARGs) in the soil. Results: Abundance of these genes was higher in the rhizospheric microbiome than in the bulk soil. Detected viral families include the plant viral family Potyviridae as well as the tailed bacteriophages of class Caudoviricetes that are mainly associated with bacterial genera Pseudomonas, Streptomyces and Mycobacterium. Viral CAZymes in this soil mainly belong to glycoside hydrolase (GH) families GH43 and GH23. Some of these CAZymes participate in a KEGG pathway with actions included debranching and degradation of hemicellulose. Other actions include biosynthesizing biopolymer of the bacterial cell wall and the layered cell wall structure of peptidoglycan. Other CAZymes promote plant physiological activities such as cell-cell recognition, embryogenesis and programmed cell death (PCD). Enzymes of other pathways help reduce the level of soil H2O2 and participate in the biosynthesis of glycine, malate, isoprenoids, as well as isoprene that protects plant from heat stress. Other enzymes act in promoting both the permeability of bacterial peroxisome membrane and carbon fixation in plants. Some enzymes participate in a balanced supply of dNTPs, successful DNA replication and mismatch repair during bacterial cell division. They also catalyze the release of signal peptides from bacterial membrane prolipoproteins. Phages with the most highly abundant antibiotic resistance genes (ARGs) transduce species of bacterial genera Pseudomonas, Streptomyces, and Mycobacterium. Abundant mechanisms of antibiotic resistance in the rhizosphere include "antibiotic efflux pump" for ARGs soxR, OleC, and MuxB, "antibiotic target alteration" for parY mutant, and "antibiotic inactivation" for arr-1. Discussion: These ARGs can act synergistically to inhibit several antibiotics including tetracycline, penam, cephalosporin, rifamycins, aminocoumarin, and oleandomycin. The study highlighted the issue of horizontal transfer of ARGs to clinical isolates and human gut microbiome.

Antioxidant Effect and Acute Oral Toxicity of Hot Springs.

According to the research, there are many illnesses for which therapeutic mineral hot springs are employed as an alternative. Its physicochemical characteristics have a substantial body of evidence. The in vivo antioxidant effect of Mosul's hot springs in Iraq has been investigated in the current investigation. An experimental design for toxicity, a control group, and a study group were created. In addition, in vivo antioxidant effect of the hot springs of Mosul, Iraq, has been studied by the lipid antiperoxidation method with (p < 0.05), in vitro by the free radical scavenging method (DPPH) for its complexing capacity of hot springs. In acute oral toxicity in vivo at fixed doses, looking for signs and symptoms of toxicity, there are no signs of intoxication or significant changes in the biochemical analysis (blood count). And, it was discovered that the variances are substantial. The animal was necropsied, and hematological and biochemical parameters were determined, as well as the organs' histological processing at the study's conclusion. It was found that the thermal waters from Mosul, Iraq, are medicinal mineral waters, chlorinated, sodium, and sulfated, nontoxic and have an antioxidant effect. With the help of the research's findings, it is hoped to provide scientific support for knowledge that, when made public, encourages the development of Mosul's hot springs as a safe and environmentally friendly tourist destination. With the results of this research, the parameters were presented with their mean and standard deviation statistics, promoting the ecological and sanitary tourism development of the Mosul hot springs, which will generate more significant income for the population, therefore growth in the region.

The Role of Natural Products and Their Multitargeted Approach to Treat Solid Cancer.

Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of cancer. These phytochemicals have demonstrated anti-carcinogenic properties by interfering with the initiation, development, and progression of cancer through altering various mechanisms such as cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. Treating multifactorial diseases, such as cancer with agents targeting a single target, might lead to limited success and, in many cases, unsatisfactory outcomes. Various epidemiological studies have shown that the steady consumption of fruits and vegetables is intensely associated with a reduced risk of cancer. Since ancient period, plants, herbs, and other natural products have been used as healing agents. Likewise, most of the medicinal ingredients accessible today are originated from the natural resources. Regardless of achievements, developing bioactive compounds and drugs from natural products has remained challenging, in part because of the problem associated with large-scale sequestration and mechanistic understanding. With significant progress in the landscape of cancer therapy and the rising use of cutting-edge technologies, we may have come to a crossroads to review approaches to identify the potential natural products and investigate their therapeutic efficacy. In the present review, we summarize the recent developments in natural products-based cancer research and its application in generating novel systemic strategies with a focus on underlying molecular mechanisms in solid cancer.

Regucalcin ameliorates doxorubicin-induced cytotoxicity in Cos-7 kidney cells and translocates from the nucleus to the mitochondria.

Doxorubicin (DOX) is a potent anticancer drug, which can have unwanted side-effects such as cardiac and kidney toxicity. A detailed investigation was undertaken of the acute cytotoxic mechanisms of DOX on kidney cells, using Cos-7 cells as kidney cell model. Cos-7 cells were exposed to DOX for a period of 24 h over a range of concentrations, and the LC50 was determined to be 7 µM. Further investigations showed that cell death was mainly via apoptosis involving Ca2+ and caspase 9, in addition to autophagy. Regucalcin (RGN), a cytoprotective protein found mainly in liver and kidney tissues, was overexpressed in Cos-7 cells and shown to protect against DOX-induced cell death. Subcellular localization studies in Cos-7 cells showed RGN to be strongly correlated with the nucleus. However, upon treatment with DOX for 4 h, which induced membrane blebbing in some cells, the localization appeared to be correlated more with the mitochondria in these cells. It is yet to be determined whether this translocation is part of the cytoprotective mechanism or a consequence of chemically induced cell stress.