Beta Elemene induces cytotoxic effects in FLT3 ITD-mutated acute myeloid leukemia by modulating apoptosis.

OBJECTIVE: ß-Elemene, a sesquiterpene with a broad anti-cancer spectrum, is particularly effective against drug-resistant and complex tumors. It can also be efficient against FLT3-expressed acute myeloid leukemia. This research aims to determine whether ß-Elemene has cytotoxic effects on FLT3 ITD-mutated AML cells. MATERIALS AND METHODS: Cytotoxicity, cell morphology, mRNA analysis with apoptotic markers, and analysis of 43 distinct protein markers related to cell death, survival, and resistance were all performed to elucidate its mechanism. Additionally, in order to understand how ß-Elemene and FLT3 interact, molecular docking, molecular dynamics simulations, and computational ADME investigations were performed. RESULTS: ß-Elemene exhibited cytotoxic activity against FLT3-mutated MV4-11 and FLT3 wild-type THP-1 cells, with an IC50 of around 25 µg/ml. The molecular studies revealed that ß-Elemene inhibited cell proliferation by inducing p53, and the involvement of p21, p27, HTRA, and HSPs were also demonstrated. The interactive inhibition in proliferation was confirmed via molecular docking and dynamics analyses. ß-Elemene occupied the FLT3 enzymatic pocket with good stability at the FLT3 active site. CONCLUSIONS: We concluded from our observations that ß-Elemene causes cell death in ITD mutant AML cells, together with the effects of stress factors and inhibiting cell division.

Significance of Orlistat in management of dyslipidemia, systolic blood pressure and body mass index.

OBJECTIVE: The current study intends to find out the efficacy of Orlistat in the management of hyperlipidemia, Systolic Blood Pressure (SBP) and Body Mass Index (BMI). MATERIALS AND METHODS: This retrospective study has evaluated the lipid profiles of the patients, who have been using metformin therapy for Type 2 diabetes. The study has obtained data regarding the parameters like triglyceride, Total cholesterol (TC), LDL cholesterol, HDL cholesterol and LDL/HDL ratio, systolic blood pressure and Body Mass Index (BMI). Random distribution of patients was done into placebo and Orlistat groups. The placebo group received only metformin, and patients in the Orlistat group received Orlistat along with metformin. After 24 weeks, the follow-up study was done, and statistical analysis was conducted. RESULTS: The study found that the Orlistat group has significant improvement (p<0.05) more improvement in LDL cholesterol, HDL cholesterol, Total cholesterol, LDL/HDL Ratio and Triglycerides, while BMI and systolic blood pressure did not show a significant difference between placebo and Orlistat group. CONCLUSIONS: This study has concluded that Orlistat can be used for significant improvement in lipid profile. The study also found that Orlistat may not have a significant effect on reducing BMI and blood pressure without adequate lifestyle modification.

Prevalence of cardiovascular disease and osteoarthritis in obese population of Hail region, Saudi Arabia.

OBJECTIVE: The aim of the study was to analyze if there was a link between chronic diseases, like cardiovascular disease (CVD) and osteoarthritis (OA), and obesity in the population of Saudi Arabia's Hail region. MATERIALS AND METHODS: The study was conducted over 12 months using an observational cross-sectional survey on 172 patients from five clinics in Hail, Saudi Arabia. A total of 172 individuals with obesity (BMI ≥ 30) finally participated in this research. The study evaluated sociodemographic variables via an electronic questionnaire with voluntary participation. RESULTS: The study found a 76% prevalence of joint pain and 77.9% prevalence of cardiovascular abnormalities. Patients with CVD were older (58±23 vs. 56±12 years) than those with OA. CVD cases were found in 42 (31.3%) males and 92 (68.7%) females, whereas OA cases were recognized in 24 (18.5%) males and 106 (81.5%) females. The occurrence of various CVDs among our participants was 43 (32%) for high cholesterol, 64 (48%) for hypertension, and 27 for both high cholesterol and hypertension (20%). Definite osteophytes were found in 28 of 24 male knees (14 right and 14 left knees) and 175 of 106 female knees (88 right knees and 87 left knees). CONCLUSIONS: The prevalence of obesity in the Hail region has continued to be a risk factor for CVD and OA in 2019 and 2020. The Saudi population has shown a higher prevalence of radiographic evidence of OA of the knee and associated symptoms than western civilizations, and preventive interventions are desperately needed in order to minimize overweight and obesity.