In this study, molecular interactions of the ligands, quercetin, gallic acid, and metformin with various diabetes mellitus-related protein targets, such as glycogen phosphorylase and peroxisome proliferator-activated receptor gamma, were assessed. It was revealed that quercetin possesses good binding affinity to both targets. Quercetin is a major constituent of methanolic extracts of Phyllanthus emblica fruit. The antihyperglycemic effect of quercetin in streptozotocin (STZ)-induced diabetic rats was examined. The isolated quercetin administered at a dose of 75 mg/kg body weight produced a maximum decrease of 14.78％in blood glucose levels in the diabetic rats after 7 days of treatment. Furthermore, quercetin doses of 50 and 75 mg/kg were shown to significantly improve the profiles of triglycerides, high-density li-poprotein, very-low-density lipoprotein, low-density lipoprotein, and total cholesterol at the end of the study in STZ-induced diabetic rats. The administration of quercetin (25, 50, and 75 mg/kg body weight) daily for 28 days in STZ-induced diabetic rats resulted in a significant decrease in blood glucose and urine sugar levels, with a considerable rise in plasma insulin and hemoglobin levels. Therefore, quercetin is a potential drug with antidiabetic and antihyperglycemic action mediated by changes in the levels of glucose, cholesterol, and triglycerides as indicated by in silico and in vivo studies.

Acetylcholinesterase (AChE) plays an important role in Alzheimer's disease (AD). The excessive activity of AChE causes various neuronal problems, particularly dementia and neuronal cell deaths. Generally, anti- AChE drugs induce some serious neuronal side effects in humans. Therefore, this study sought to identify alternative drug molecules from natural products with fewer side effects than those of conventional drugs for treating AD. To achieve this, we developed computational methods for predicting drug and target binding affinities using the Schrodinger suite. The target and ligand molecules were retrieved from established databases. The target enzyme has 539 amino acid residues in its sequence alignment. Ligand molecules of 20 bioactive molecules were obtained from different kinds of plants, after which we performed critical analyses such as molecular docking; molecular dynamic (MD) simulations; and absorption, distribution, metabolism, and excretion (ADME) analysis. In the docking studies, the natural compound rutin showed a superior docking score of -12.335 with a good binding energy value of -73.313 kcal/mol. Based on these findings, rutin and the target complex was used to perform MD simulations to analyze rutin stability at 30 ns. In conclusion, our study demonstrates that rutin is a superior drug candidate for AD. Therefore, we propose that this molecule is worth further investigation using in vitro studies.

Objective: Primary sarcoma of the cervix is rare and is associated with worse outcomes as compared to other histologies. The purpose of this study was to identify national treatment patterns and outcomes based on histological subtype using the National Cancer Database (NCDB). Methods: The NCDB was queried for patients with cervical cancer from 2004–2015. Clinico-demographic treatment details were obtained and compared between patients with squamous cell carcinoma (SCC), adenocarcinoma, and sarcoma of the cervix. Multivariable Cox regression and the Kaplan-Meier method was used to examine survival. Results: 107,177 patients met inclusion criteria including 81,245 (75.8%) women with SCC, 24,562 (22.9%) women with adenocarcinoma, and 1,370 (1.3%) women with sarcoma. Of the patients with cervical sarcoma, 680 (49.6%) patients had carcinosarcoma or malignant mixed Müllerian tumor, 255 (18.6%) patients had leiomyosarcoma, 197 (14.4%) patients had adenosarcoma, 28 (2.0%) patients had endometrial stromal sarcoma (ESS), 85 (6.2%) patients had rhabdomyosarcoma, and 125 (9.1%) patients had sarcoma not otherwise specified (NOS). Patients with sarcoma were older and more likely to be treated primarily with surgery. On multivariable Cox regression, sarcoma had decreased overall survival (OS) as compared to patients with SCC (hazard ratio=2.17; 95% CI=1.99–2.37; p<0.001). Among patients with sarcoma, 5-year OS was 89.2% for adenosarcoma, 66.2% for rhabdomyosarcoma, 55.6% for leiomyosarcoma, 45.8% for ESS, 31.6% for carcinosarcoma, and 29.2% for sarcoma NOS. Conclusions Primary cervical sarcomas have inferior outcomes compared to SCC and adenocarcinoma. Sarcoma NOS and carcinosarcoma have the worst prognosis among sarcoma subtypes.

Objective: Melanoma comprises 5% to 10% of vulvar cancers and prognosis is poor. The purpose of this study was to identify prognostic factors and treatment patterns for vulvar melanoma using the National Cancer Database (NCDB). Methods: The NCDB was queried for patients with invasive vulvar melanoma from 2004–2015. Descriptive statistics were generated to describe clinical and treatment details.Multivariable Cox regression and the Kaplan-Meier method were used to examine overall survival (OS). Results: 1,917 patients with vulvar melanoma met inclusion criteria. Median follow-up time was 32 months (range, 0–151 months). Older age, larger tumor size, advanced disease stage, increased Charlson-Deyo comorbidity score, and care at a non-academic center were independent predictors for decreased OS. Surgical management of the primary site, lymph node surgery, and insurance provided a significant survival benefit. Use of immunotherapy for vulvar melanoma has increased over time. Two-year OS with immunotherapy in patients with distant metastatic disease was higher, although this did not reach statistical significance (33% vs. 12%, p=0.054). Conclusions Vulvar melanoma has a poor prognosis for those with regional and distant metastatic disease. Extent of disease, tumor size, and patient age are important prognostic factors. Other favorable factors included insurance and surgical management. The use of immunotherapy has increased over time and may improve survival in those with distant disease. These data support further investigation into the role of immunotherapy for vulvar melanoma to optimize outcomes.