Repurposing of USFDA-approved drugs to identify leads for inhibition of acetylcholinesterase enzyme: a plausible utility as an anti-Alzheimer agent.

In the quest to identify new anti-Alzheimer agents, we employed drug repositioning or drug repositioning techniques on approved USFDA small molecules. Herein, we report the structure-based virtual screening (SBVS) of 1880 USFDA-approved drugs. The in silico-based identification was followed by calculating Prime MMGB-SA binding energy and molecular dynamics simulation studies. The cumulative analysis led to identifying domperidone as an identified hit. Domperidone was further corroborated in vitro using anticholinesterase-based assessment, keeping donepezil as a positive control. The analysis revealed that the identified lead (domperidone) could induce an inhibitory effect on AChE in a dose-dependent manner with an IC50 of 3.67 µM as compared to donepezil, which exhibited an IC50 of 1.37 µM. However, as domperidone is known to have poor BBB permeability, we rationally proposed new analogues utilizing the principles of bioisosterism. The bioisostere-clubbed analogues were found to have better BBB permeability, affinity, and stability within the catalytic domain of AChE via molecular docking and dynamics studies. The proposed bioisosteres may be synthesized in the future. They may plausibly be explored for their implication in the developmental progress of new anti-Alzheimer agent achieved via repurposing techniques in future.

The impact of electronic cigarette use on periodontitis and periodontal outcomes: a systematic review and meta-analysis.

BACKGROUND: Periodontitis, a prevalent inflammatory disease affecting tooth-supporting structures, leads to significant oral health and systemic complications if untreated. While traditional smoking is a well-known risk factor for periodontitis, the impact of electronic cigarettes (e-cigarettes) on periodontal health remains unclear. This systematic review and meta-analysis aim to synthesize existing evidence on the effects of e-cigarette use on periodontitis and other periodontal outcomes. METHODS: A literature search was conducted across PubMed, EMBASE, and Web of Science from their inception up to June 15 2024. Eligible studies included those assessing the impact of e-cigarette use on periodontal outcomes such as bleeding on probing (BOP), plaque index, probing depth, clinical attachment loss, and marginal bone loss. Data were extracted and analyzed using random-effect models to calculate pooled mean differences. R statistical software was used to perform meta-analyses. RESULTS: Twelve studies were included in the meta-analysis. E-cigarette users showed a significantly lower mean BOP score compared to non-users (pooled mean difference: -14.233; 95% CI: -20.424 to -8.043; I² = 99%). For other periodontal outcomes, the findings were as follows: Plaque Index (MD: -0.160; 95% CI: -0.680 to 0.360; I² = 95%), Clinical Attachment Loss (MD: 0.120; 95% CI: -0.045 to 0.285; I² = 90%), Probing Depth (MD: 0.056; 95% CI: -0.070 to 0.182; I² = 85%), and Marginal Bone Loss (MD: -0.052; 95% CI: -0.168 to 0.064; I² = 88%). CONCLUSION: Present studies have not identified a significant link between e-cigarette use and adverse effects on periodontal health, but the available research is limited. Further longitudinal research is necessary to evaluate the long-term effects of e-cigarette use on periodontal health and to clarify any associated risks.

Predictors of acute kidney injury in dengue patients: a systematic review and meta-analysis.

BACKGROUND: Dengue infection poses a significant global health challenge, particularly in tropical and subtropical regions. Among its severe complications, Acute kidney injury (AKI) stands out due to its association with increased morbidity, mortality, and healthcare burdens. This Meta-analysis aim to identify and evaluate the predictors of AKI among dengue patients, facilitating early detection and management strategies to mitigate AKI's impact. METHODS: We searched PubMed, EMBASE, and Web of Science databases, covering literature up to February 2024. We included human observational studies reporting on AKI predictors in confirmed dengue cases. Nested-Knowledge software was used for screening and data extraction. The Newcastle-Ottawa Scale was used for quality assessment. R software (V 4.3) was utilized to compute pooled odds ratios (ORs) and 95% confidence intervals (CIs) for each predictor. RESULTS: Our search yielded nine studies involving diverse geographic locations and patient demographics. A total of 9,198 patients were included in the studies, with 542 diagnosed with AKI. in which key predictors of AKI identified include severe forms of dengue (OR: 2.22, 95% CI: 1.02-3.42), male gender (OR: 3.13, 95% CI: 1.82-4.44), comorbidities such as diabetes mellitus (OR: 3.298, 95% CI: 0.274-6.322), and chronic kidney disease (OR: 2.2, 95% CI: 0.42-11.24), as well as co-infections and clinical manifestations like rhabdomyolysis and major bleeding. CONCLUSION: Our study identifies several predictors of AKI in dengue patients. These findings indicate the importance of early identification and intervention for high-risk individuals. Future research should focus on standardizing AKI diagnostic criteria within the dengue context and exploring the mechanisms underlying these associations to improve patient care and outcomes.

Exploring the Insights on Exosomes and their Utility in Treating Ophthalmic Disease: Delving into the Clinical Approval and Present Trials.

Ophthalmic diseases include a wide array of conditions, each requiring individualized treatment approaches. In ophthalmic research and as therapeutics against potential pharmacological indications, several subtypes of exosomes (EVs) have been reconnoitered, mainly for their regenerative, neuroprotective, and anti-inflammatory characteristics. EVs are recently gaining wider attention as promising vehicles for therapies because of their natural participation in communication between cells and targeted delivery. These small vesicles, derived from cells, transport numerous molecules between cells, thus contributing advantages like low immunogenicity, stability, and the ability to target cells specifically. These inherent advantages of carrying the therapeutic cargo and enabling intercellular signaling make them a captivating avenue for progressing ophthalmic disease treatment options. While research is ongoing, and clinical applications are still emerging, several EV subtypes have shown promise for possible applications in addressing several ophthalmic diseases, such as glaucoma, age-related macular degenerative disorders, retinal degenerative disorders, and ocular inflammatory conditions.

Advancements in targeting tumor suppressor genes (p53 and BRCA 1/2) in breast cancer therapy.

Globally, among numerous cancer subtypes, breast cancer (BC) is one of the most prevalent forms of cancer affecting the female population. A female's family history significantly increases her risk of developing breast cancer. BC is caused by aberrant breast cells that proliferate and develop into tumors. It is estimated that 5-10% of breast carcinomas are inherited and involve genetic mutations that ensure the survival and prognosis of breast cancer cells. The most common genetic variations are responsible for hereditary breast cancer but are not limited to p53, BRCA1, and BRCA2. BRCA1 and BRCA2 are involved in genomic recombination, cell cycle monitoring, programmed cell death, and transcriptional regulation. When BRCA1 and 2 genetic variations are present in breast carcinoma, p53 irregularities become more prevalent. Both BRCA1/2 and p53 genes are involved in cell cycle monitoring. The present article discusses the current status of breast cancer research, spotlighting the tumor suppressor genes (BRCA1/2 and p53) along with structural activity relationship studies, FDA-approved drugs, and several therapy modalities for treating BC. Breast cancer drugs, accessible today in the market, have different side effects including anemia, pneumonitis, nausea, lethargy, and vomiting. Thus, the development of novel p53 and BRCA1/2 inhibitors with minimal possible side effects is crucial. We have covered compounds that have been examined subsequently (2020 onwards) in this overview which may be utilized as lead compounds. Further, we have covered mechanistic pathways to showcase the critical druggable targets and clinical and post-clinical drugs targeting them for their utility in BC.

Exploring anticancer properties of the phytoconstituents and comparative analysis of their chemical space parameters with USFDA-approved synthetic anticancer agents.

The present review article thoroughly analyses natural products and their derived phytoconstituents as a rich source of plausible anticancer drugs. The study thoroughly explores the chemical components derived from various natural sources, thus emphasizing their unique structural characteristics and therapeutic potential as an anticancer agent. The review contains the critical chemical constituents' in-depth molecular mechanisms, their source's chemical structures and the categories. The review also comprises an exhaustive and comprehensive analysis of different chemical spacing parameters of the anticancer agents derived from natural products. It compares them with USFDA-approved synthetic anticancer drugs up to 2020, thus providing a meaningful understanding of the relationship between natural and synthetic compounds portraying the anticancer assets. The review also delves more deeply into the chemical analysis of the heterocyclic moieties from the natural product arena, illustrating the anticancer mechanisms. The present article is, therefore, expected to serve as a valuable resource for natural product and medicinal chemists, encouraging and promoting an integrated approach to exploit the potential of natural products in drug discovery development and translational research, which have a prerequisite of bench to bedside approach. The work could guide researchers toward innovative approaches for the ever-evolving field of anticancer drug discovery.

Rhizobacterial mediated interactions in Curcuma longa for plant growth and enhanced crop productivity: a systematic review.

Turmeric (Curcuma longa L.), a significant commercial crop of the Indian subcontinent is widely used as a condiment, natural dye, and as a cure for different ailments. Various bioactive compounds such as turmerones and curcuminoids have been isolated from C. longa that have shown remarkable medicinal activity against various ailments. However, reduced soil fertility, climatic variations, rapid urbanization, and enhanced food demand, pose a multifaceted challenge to the current agricultural practices of C. longa. Plant growth-promoting microbes play a vital role in plant growth and development by regulating primary and secondary metabolite production. Rhizospheric associations are complex species-specific interconnections of different microbiota with a plant that sustain soil health and promote plant growth through nutrient acquisition, nitrogen fixation, phosphate availability, phytohormone production, and antimicrobial activities. An elaborative study of microbiota associated with the roots of C. longa is essential for rhizospheric engineering as there is a huge potential to develop novel products based on microbial consortium formulations and elicitors to improve plant health, stress tolerance, and the production of secondary metabolites such as curcumin. Primarily, the purpose of this review is to implicate the rhizospheric microbial flora as probiotics influencing overall C. longa health, development, and survival for an increase in biomass, enhanced yield of secondary metabolites, and sustainable crop production.

Biochemical characterization and pharmacognostic evaluation of purified catechins in green tea (Camellia sinensis) cultivars of India.

Green tea (GT) is derived from the leaves of Camellia sinensis implicated in a wide range of health attributes. In the present comprehensive study, methanolic, acetone and aqueous extract of leaves of C. sinensis var. sinensis [Kashmir (KW), Uttarakhand (IP & PN)] and C. sinensis var. assamica (Assam, AT) were explored for their phytoconstituents. Solvent extracts of GT cultivars showed rich presence of phytoconstituents in comparison with aqueous extracts. The methanolic extract of AT and acetone extract of KW showed highest total phenol content (18.32 ± 0.357 mg of GAE equivalent/g of sample) and total flavonoid content (29.25 ± 0.015 mg of catechin equivalent/g of sample), respectively. All the cultivars revealed higher free radical scavenging activity in the range of 73.80 ± 0.152 to 82.40 ± 0.004 % confirming antioxidant potentials. The HPLC analysis of purified residue procured from solvent partitioning depicted AT with highest concentration of epigallocatechin gallate (EGCg) i.e., 154.7 ± 4.949 mg/g followed by Kashmir and Uttarakhand GT cultivars. The present study revealed that Assam GT could be a potent herbal candidate with multiple nutraceutical applications. However, significant investigation of the cultivars is to be done to further explore the EGCg-dependent activity of GT for herbal drug development.