Phenylstyrylpyrimidine derivatives as potential multipotent therapeutics for Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurological disorder that affects millions of people worldwide. Despite extensive research efforts, there are currently no effective disease-modifying therapeutics available for the complete cure of AD. In the current study, we have designed and synthesized a series of phenyl-styryl-pyrimidine derivatives as potential multifunctional agents against different targets of AD. The compounds were evaluated for their ability to inhibit acetylcholinesterase (AChE), monoamine oxidase (MAO) and ß amyloid aggregation which are associated with the initiation and progression of the disease. Several compounds in the series exhibited potent inhibitory activity against AChE and MAO-B, with IC50 values in the low micromolar range. In particular, two compounds, BV-12 and BV-14, were found to exhibit a multipotent profile and showed non-competitive inhibition against MAO-B with IC50 values of 4.93 ± 0.38 & 7.265 ± 0.82 µM, respectively and AChE inhibition with IC50 values of 7.265 and 9.291 µM, respectively. BV-12 and BV-14 also displayed ß amyloid self-aggregation inhibition of 32.98% and 23.25%, respectively. Furthermore, molecular modelling studies revealed that BV-14 displayed a docking score of -11.20 kcal mol-1 with MAO-B & -6.767 kcal mol-1 with AChE, forming a stable complex with both proteins. It was concluded that phenyl-styryl-pyrimidine derivatives have the potential to be developed as multitarget directed ligands for the treatment of AD.

Medical Student Mentorship for Undergraduate Students Underrepresented in Medicine Improves Confidence and Knowledge About Medical School Application.

Purpose Applying to medical school is accompanied by significant barriers to prospective applicants. Students who are underrepresented in medicine (URiM) may face additional barriers. We created a mentorship program to pair pre-medical URiM students with medical student mentors. The purpose of this study was to determine if providing mentorship and resources to URiM pre-medical students increased their knowledge and confidence regarding the medical school application process. Method A survey was emailed to mentees of the program to assess their knowledge and confidence about the Medical College Admission Test (MCAT) and medical school application before and after receiving mentorship. Wilcoxon-Signed-Rank tests were used for data analysis. Results A total of 28 participants completed the pilot study of which 17 gave qualitative feedback. Students reported feeling significantly more knowledgeable and confident after six months of enrollment on seven (77.8%) of the survey items. Respondents agreed that mentorship was the most valuable aspect of the program, with 13 (76.5%) respondents qualitatively endorsing the positive impact mentorship imparted to them. Conclusion Having a medical student mentor helped URiM pre-medical students feel more knowledgeable and confident about the medical school application process. By providing URiM students with additional resources, the diversity of future classes of physicians may improve and better mirror the populations they will serve.

Mechanistic Evaluation of miRNAs and Their Targeted Genes in the Pathogenesis and Therapeutics of Parkinson's Disease.

MicroRNA (miRNA) are usually 18-25 nucleotides long non-coding RNA targeting post-transcriptional regulation of genes involved in various biological processes. The function of miRNA is essential for maintaining a homeostatic cellular condition, regulating autophagy, cellular motility, and inflammation. Dysregulation of miRNA is responsible for multiple disorders, including neurodegeneration, which has emerged as a severe problem in recent times and has verified itself as a life-threatening condition that can be understood by the continuous destruction of neurons affecting various cognitive and motor functions. Parkinson's disease (PD) is the second most common, permanently debilitating neurodegenerative disorder after Alzheimer's, mainly characterized by uncontrolled tremor, stiffness, bradykinesia or akinesia (slowness in movement), and post-traumatic stress disorder. PD is mainly caused by the demolition of the primary dopamine neurotransmitter secretory cells and dopaminergic or dopamine secretory neurons in the substantia nigra pars compacta of the midbrain, which are majorly responsible for motor functions. In this study, a systematic evaluation of research articles from year 2017 to 2022 was performed on multiple search engines, and lists of miRNA being dysregulated in PD in different body components were generated. This study highlighted miR-7, miR-124, miR-29 family, and miR-425, showing altered expression levels during PD's progression, further regulating the expression of multiple genes responsible for PD.