Venetoclax analogs as promising anticancer therapeutics via targeting Bcl-2 protein: in-silico drug discovery study.

B-cell lymphoma 2 (Bcl-2) protein plays a vital role in enhancing malignant cell survival by alleviating programmed cell death. Therefore, Bcl-2 protein has been identified as a charming druggable target for cancer treatment. Venetoclax has enticed considerable attention as a potential Bcl-2 inhibitor. Herein, in-silico computations were executed to search for new venetoclax analogs against the Bcl-2 protein. A library involving 4112 was collected, prepared, and virtually screened against Bcl-2 protein using AutoDock Vina1.1.2 software. Promising analogs in complex with Bcl-2 protein were further submitted to molecular dynamics (MD) simulations, pursued by binding energy computations using the MM-GBSA approach. Compared to venetoclax (ΔGbinding = -51.2 kcal/mol), PubChem-873-158-83 and PubChem-148-422-478 demonstrated greater binding affinities with Bcl-2 protein throughout 100 ns MD simulations with ΔGbinding values of -69.1 and -62.4 kcal/mol, respectively. Structural and energetical analyses unveiled good stabilization of the identified analogs complexed with Bcl-2 protein over the MD course. The pharmacokinetic features of the two identified analogs were anticipated and unveiled the oral bioavailability of these compounds. Further in-vitro/in-vivo biological evaluations around these compounds could assist in identifying anticancer leads towards Bcl-2 protein.Communicated by Ramaswamy H. Sarma.

Nutritional quality traits of raw and cooked Ark shell (Bivalvia: Arcidae): balancing the benefits and risks of seafood consumption.

Biochemical composition and fatty acid profile of raw Ark shells (RA) were compared to Ark shells submitted to three different cooking methods (BA: baking in the oven; PF: pan-frying in butter and MW: cooking in a microwave). Moisture (%) was significantly higher in RA (79.66) with respect to PF (65.09), BA (48.63) and MW (47.02). Protein (mg/g of flesh) decreased significantly from 18.62 in RA to 15.40 in MW, 13.76 in PF and 13.33 in BA. However, lipids significantly increased in MW (43.32 mg/g of flesh) and PF (63.63 mg/g of flesh) with respect to RA (35.05 mg/g of flesh). Pan-frying affected considerably triacylglycerol (TAG) and the fatty acid composition (FA) of Ark shell flesh. The most changes occurred in saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acid fractions after this process. The n-3 PUFA decreased significantly from RA (16.40 mg/g dry weight) to PF (10.02 mg/g DW). While, the opposite trend was observed for n-6 PUFA, revealing that this cooking method had considerable effects on the nutritional characteristics of this edible shellfish. The analysis of lipid peroxidation markers such as thiobarbituric acid reactive substances, free fatty acid and peroxide value confirmed that both heat treatment and time of cooking caused lipid degradation, which had been more accentuated during pan-frying treatment. For the populations who consume Ark shells occasionally or frequently, baking and microwave cooking could be then considered as wiser and healthier cooking methods since they conserve better the nutritional value of this marine product. The present study will be of practical value from a health perspective for Mediterranean populations.

Trace elements and oxidative stress in the Ark shell Arca noae from a Mediterranean coastal lagoon (Bizerte lagoon, Tunisia): are there health risks associated with their consumption?

The current study examined the concentrations of ten trace elements (TE) (nickel, chromium, cadmium, iron, zinc, manganese, aluminum, copper, selenium and lead) in the edible tissue of the Ark shell Arca noae (L. 1758) from a Mediterranean coastal lagoon, the Bizerte lagoon during 2013-2014. The analysis of several redox status biomarkers, metallothioneins (MTs), malondialdehyde (MDA), glutathione peroxidase (GPx), reduced glutathione (GSH) and acetylcholinesterase (AChE), was monitored as a response to TE bioaccumulation and environmental parameters variability. Significant differences (p < 0.05) were observed between mean seasonal TE concentrations in A. noae soft tissue. The highest TE concentrations in A. noae soft tissues were recorded during summer, which coincided with the increase of body dry weight (BDW) and the gonad index (GI). During this season, biomarker responses were enhanced, revealing significant increases of MTs, MDA and GSH levels as well as GPx activity in A. noae tissues, while a decrease of AChE activity was observed. The levels of TE analyzed in A. noae and several parameters used to assess the potential human risk (estimated weekly intake, target hazard quotient and target hazard risk) were lower than the permissible limits for safe seafood consumption. Consequently, this shellfish can be considered safe for human consumption. This preliminary study presents prospects for the valorization of this seafood product in Tunisia's food sector. It also gives basal information for future environmental assessment studies in which A. noae could be used as early warning tools in the field of biomonitoring programs and confirms the usefulness of biomarkers to monitor the health status of aquatic organisms.