Targeting fatty acid uptake and metabolism in cancer cells: A promising strategy for cancer treatment.

Despite scientific development, cancer is still a fatal disease. The development of cancer is thought to be significantly influenced by fatty acids. Several mechanisms that control fatty acid absorption and metabolism are reported to be altered in cancer cells to support their survival. Cancer cells can use de novo synthesis or uptake of extracellular fatty acid if one method is restricted. This factor makes it more difficult to target one pathway while failing to treat the disease properly. Side effects may also arise if several inhibitors simultaneously target many targets. If a viable inhibitor could work on several routes, the number of negative effects might be reduced. Comparative investigations against cell viability have found several potent natural and manmade substances. In this review, we discuss the complex roles that fatty acids play in the development of tumors and the progression of cancer, newly discovered and potentially effective natural and synthetic compounds that block the uptake and metabolism of fatty acids, the adverse side effects that can occur when multiple inhibitors are used to treat cancer, and emerging therapeutic approaches.

Assessment of antidiabetic activity of three Phenylspirodrimanes from fungus Stachybotrys chartarum MUT 3308 by ADME, QSAR, molecular docking and molecular dynamics simulation studies against protein tyrosine phosphatase 1B (PTP1B).

Phenylspirodrimanes (PSD) are the sesquiterpene quinone type meroterpenoids found in nature. PSDs are found to exhibit inhibitory activity against immunocomplex diseases, and tyrosine kinase receptors. Three of the different PSDs C1, C2, and C3 that have been reported to be isolated from the sponge-associated fungus Stachybotrys chartarum MUT 3308 are selected for studying their possible inhibitory effect against type 2 diabetes mellitus. Mechanistically, blocking protein tyrosine phosphatase 1B (PTP1B) helps to reduce the insulin resistance induction caused by the high expression of PTP1B. The QSAR, ADME, toxicity (T) study was carried out to predict the pharmacokinetic properties and the biological activities of the PSDs. PASS prediction web tool was used to find and select the target proteins 1NNY, and 2HNP. According to the molecular docking simulations, C1 and C2 showed better binding affinity of -8.5 kcal/mol, and -8.1 kcal/mol respectively against 1NNY compared to the control ligand. RMSD, RMSF, Rg, and SASA analysis revealed that both C1, and C2 showed better stability, minor conformational changes, and minor fluctuation upon binding to PTP1B. Protein contact analysis was carried out to validate the residues that are in contact with the ligands according to molecular docking studies. Overall, C1, and C2 could be proposed as novel natural hits to be developed and small modifications of these PSDs could result in inducing the binding affinity significantly, although experimental validation is required for further evaluation of the work.Communicated by Ramaswamy H. Sarma.

Prospective study of de novo sexual dysfunction after anterior urethroplasty: Causative factors, incidence, and recovery of function - A single-center experience.

OBJECTIVES: The objectives of this study were to evaluate the effect of single-stage anterior urethroplasty on sexual function by considering age, stricture length, location, and different surgical techniques. Incidence of postoperative sexual dysfunction (SD) and probability of recovery were also highlighted. MATERIALS AND METHODS: A total of 115 patients undergoing anterior urethroplasty from February 2016 to June 2020 were evaluated prospectively. Patients were categorized on the basis of age, location, length of stricture as well as surgical techniques. We evaluated three domains of sexual function (erectile, orgasmic, and overall satisfaction) using the International Index of Erectile Function (IIEF) preoperatively and then after 3 months and 6 months postoperatively in follow-up. Pre- and postoperative IIEF values were compared. RESULTS: The mean age was 41.7 ± 13.9 years. There was a significant decrease in postoperative IIEF score from the preoperative value in older patients (>40 years) along with poor recovery at the 6th month as compared to patients of younger age group (≤40 years). However, there was a significant reduction of sexual function postoperatively in case of longer stricture segment, panurethral stricture, bulbar urethral stricture, dorsal buccal mucosal urethroplasty, and excision-primary anastomosis technique in univariate analysis, but on multivariate analysis, only age was proved to be an independent predictor of de novo SD which was found in a total of 28 patients (24.3%). CONCLUSION: Overall, anterior urethroplasty does not influence postoperative sexual function, whereas only older patients have a poor outcome. Most of the younger patients recover completely by 6 months.

Sexual function outcomes and risk factors of erectile dysfunction after surgical repair of penile fracture.

OBJECTIVE: To determine the erectile dysfunction (ED), overall sexual function, and risk factors for developing ED after surgical repair of penile fracture. MATERIAL AND METHODS: This was an ambispective observational study conducted from September 2014 to August 2019, which included 68 patients with a clinical diagnosis of penile fracture. The clinical presentation, etiology, and surgical details were recorded. Patients were contacted via telephone and called for follow-up. Their sexual function was objectively recorded using the sexual health inventory for men questionnaire, erection hardness grading scale, and the brief male sexual function inventory (BMSFI). Patients were categorized in 2 groups on the basis of ED. These 2 groups were compared on the basis of preoperative and intraoperative factors to determine the predictors of postoperative ED. RESULTS: The mean age at presentation was 33.64±9.46 (range, 19-54) years. The most common mode of injury was injury during the sexual intercourse (78%). All the patients underwent surgical exploration through subcoronal degloving incision. On follow-up, 7 patients (11.3%) developed ED (mild ED, 5 patients; mild-to-moderate ED, 2 patients). Per BMSFI, 58 (93.5%) patients had no bothersome issues with their sexual life, and they were mostly satisfied. The significant risk factors for ED were age >50 years and bilateral corporal involvement. CONCLUSION: Penile fracture is a true urological emergency, and prompt diagnosis by clinical acumen and emergent surgical exploration provide good functional results with low morbidity. The main predictors of postsurgical ED are increasing age (>50 years) and bilateral corporal involvement.