Multitargeted Virtual Screening and Molecular Simulation of Natural Product-like Compounds against GSK3ß, NMDA-Receptor, and BACE-1 for the Management of Alzheimer's Disease.

The complexity of Alzheimer's disease (AD) and several side effects of currently available medication inclined us to search for a novel natural cure by targeting multiple key regulatory proteins. We initially virtually screened the natural product-like compounds against GSK3ß, NMDA receptor, and BACE-1 and thereafter validated the best hit through molecular dynamics simulation (MDS). The results demonstrated that out of 2029 compounds, only 51 compounds exhibited better binding interactions than native ligands, with all three protein targets (NMDA, GSK3ß, and BACE) considered multitarget inhibitors. Among them, F1094-0201 is the most potent inhibitor against multiple targets with binding energy -11.7, -10.6, and -12 kcal/mol, respectively. ADME-T analysis results showed that F1094-0201 was found to be suitable for CNS drug-likeness in addition to their other drug-likeness properties. The MDS results of RMSD, RMSF, Rg, SASA, SSE and residue interactions indicated the formation of a strong and stable association in the complex of ligands (F1094-0201) and proteins. These findings confirm the F1094-0201's ability to remain inside target proteins' binding pockets while forming a stable complex of protein-ligand. The free energies (MM/GBSA) of BACE-F1094-0201, GSK3ß-F1094-0201, and NMDA-F1094-0201 complex formation were -73.78 ± 4.31 kcal mol-1, -72.77 ± 3.43 kcal mol-1, and -52.51 ± 2.85 kcal mol-1, respectively. Amongst the target proteins, F1094-0201 have a more stable association with BACE, followed by NMDA and GSK3ß. These attributes of F1094-0201 indicate it as a possible option for the management of pathophysiological pathways associated with AD.

Monkeypox: An Unfamiliar Virus-Clinical and Epidemiological Characteristics, Diagnosis, and Treatment with Special Emphasis on Oral Health.

With the recent increased prevalence of human outbreaks, monkeypox has been recognized for decades as an infectious disease with substantial pandemic potential. The majority of cases of this virus have been observed in the European region (11,865), with few cases in the Western Pacific (54). Various governing health agencies are striving to restrain the fatal monkeypox virus (MPXV). Health practitioners around the world are learning about the many clinical manifestations of this infection, and its potential therapies. Despite the plethora of new evidence and rising cases, the essential questions remain unsolved. Thus, in this review, we have modernized the outlook for monkeypox, which will be helpful for various medical practitioners. In the light of continuing outbreaks around the world, we have also presented our assessment of the readiness of India against this outbreak, with a special focus on its effects on oral health.

Effects of Yogic Interventions on Patients Diagnosed With Cardiac Diseases. A Systematic Review and Meta-Analysis.

Objective: Presently, evidence-based research studies on the efficacy of complimentary therapies like yoga for patients with different cardiac diseases are limited and conflicting. The objective of this study is to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) on yogic interventions compared with usual care or non-pharmacological treatment in patients diagnosed with cardiac diseases. Methods: We conducted an electronic search of literature published from 2006 to May 2021 through five databases. PRISMA statement was used to develop and report a systematic review and meta-analysis protocol. Sixteen RCTs were included in the systematic review and 11 RCTs were used for meta-analysis. Outcome measures were blood pressure, lipid profile, and psychosocial measures. The Cochrane collaboration tool was used to assess bias risk. Results: The results show that yogic interventions resulted in significant reduction in systolic (d = 046; 95% CI.08-0.84; I2 = 81.86%) and diastolic blood pressures (d = 0.56; 95% CI.13-0.99, I2 = 84.84%). A medium statistically significant increase in HDL (d =0.67; 95% CI 0 to 1.33; I2 79.7%) and a low but significant effect on LDL (d = 0.23; 95% CI -0.08-0.54; I2 32.61%), total cholesterol (d =0.28; 95% CI -0.14-0.7; I2 63.72%), and triglycerides (d = 0.43; 95% CI -0.1-0.97; I2 76.64%) were observed. Pooled effect sizes showed a medium to low statistically significant effect on psychosocial indicators viz., QoL, stress, anxiety, and depression. Conclusion: The meta-analysis found strong evidence of effectiveness of yogic interventions on lipid profile, blood pressure, and psychosocial outcomes in patients with diagnosed cardiac diseases.