Discovery, synthesis and in combo studies of Schiff's bases as promising dipeptidyl peptidase-IV inhibitors.

Diabetes mellitus is a main global health apprehension. Macrovascular illnesses, neuropathy, retinopathy, and nephropathy are considered some of its severe hitches. Gliptins are a group of hypoglycemic agents that inhibit dipeptidyl peptidase-IV (DPP-IV) enzyme and support blood glucose-lowering effect of incretins. In the current research, synthesis, characterization, docking, and biological evaluation of fourteen Schiff's bases 5a-f and 9a-h were carried out. Compound 9f revealed the best in vitro anti-DPP-IV activity of 35.7% inhibition at a concentration of 100 µM. Compounds 9c and 9f with the highest in vitro DPP-IV inhibition were subjected to the in vivo glucose-lowering test using vildagliptin as a positive inhibitor. Vildagliptin, 9c, and 9f showed significant reduction in the blood glucose levels of the treated mice after 30 min of glucose administration. Moreover, induced fit docking showed that these derivatives accommodated the enzyme binding site with comparable docking scores. Schiff's bases can serve as promising lead for the development of new DPP-IV inhibitors.

Validity of mini-fluid challenge for predicting fluid responsiveness following liver transplantation.

BACKGROUND: Mini-fluid challenge is a well tested and effective tool to predict fluid responsiveness under various clinical conditions. However, mini-fluid challenge has never been tested in patients with end-stage liver disease. This study investigated whether infusion of 150 ml albumin 5% can predict fluid responsiveness in cirrhotic patients following liver transplant. METHODS: Fifty patients receiving living donor liver transplant were included in the analysis. Mini-fluid challenge composed of 150 ml of albumin 5% administered over 1 min in three consecutive 50-ml fluid boluses. An additional 350 ml was then infused at a constant rate over 15 min (for a total of 500 ml). Stroke volume (SV) was measured as the product of the subaortic velocity time integral (VTI) and left ventricular outflow tract (LVOT) area. Fluid responsiveness was defined as an increase in SV by ≥15% after the infusion. RESULTS: Fifty patients were enrolled in the study. Fourteen patients were classified with Child A, 15 patients with Child B, and 21 patients with Child C cirrhosis. Thirty four patients were fluid responders and 16 patients were fluid non-responders. After 150 ml of albumin 5%, the SV increased significantly in our cohort. The area under receiver operating curve (AUROC) was 0.7 (95% confidence interval [CI] 0.5-0.8, P = 0.005). In subgroup analysis, the SV increased significantly after mini fluid challenge in the Child A group (P = 0.017) but not Child B or C groups (P = 0.3 and 0.29, respectively). The AUROC for mini-fluid challenge in the Child A group was 0.86 (95% confidence interval [CI] 0.6-0.9, P = 0.0004), while mini-fluid challenge failed to discriminate between responders and non-responders in Child B and C groups. CONCLUSION: A mini-fluid challenge of 150 ml albumin 5% can predict fluid responsiveness in liver transplant patients with fair sensitivity and specifiicty. Subgroup analyis revealed that minifluid challenge can predict fluid responsiveness in patients with Child A cirrhosis but not patients with Child B or C cirrhosis. TRIAL REGISTRATION: NCT03396159 . (Prospective registered). Initial registration date was 10/01/2018.

Lycopene as a Potential Bioactive Compound: Chemistry, Extraction, and Anticancer Prospective.

Lycopene, a potential bioactive agent, is a non-pro-vitamin A carotenoid recognized as a potent antioxidant. It is extracted from plants like tomatoes, watermelons, red carrots and papayas and has remarkable health benefits. A significant amount of research has been assisted to date to establish the anticancer activity of lycopene. Our review enhances information about the promising anticancer potential of this compound. The biological activity of lycopene has been described in several studies in regard to pancreatic, breast, prostate, liver, gastric, ovarian, kidney, skin, intestine, brain and spinal cord cancers. Lycopene resists cancer by inhibition of apoptosis, induction of cell proliferation, cell invasion, cell cycle development, metastasis and angiogenesis. The mechanisms of anticancer action of lycopene are attributed to the management of certain signal transduction pathways, such as modulation of insulin-like growth factors system, PI3K/Akt pathway, modification of important gene expression, inhibit the activity of sex steroid hormones, and the conversation of mitochondrial behavior. Hence, this review focuses on current knowledge of sources, extraction techniques, and chemistry of lycopene, as well as the prospective mechanisms of action related with its anticancer activity. Also, it summarizes the background information about lycopene and the most current research with consideration to its aspect in treating several types of cancer together with future directions.