The selected low doses of 3AB rather than the higher dose (15 mg/kg) protected against radiation-induced multiple organ damage.

Current results document for the first time, a cross-talk between TuM2-PK and each of CRP and CA 15-3 in metastatic breast cancer.

Silent information regulator 1 (SIRT-1), a nicotinamide adenine dinucleotidedependent deacetylase, was found to regulate cell apoptosis, inflammation, and oxidative stress response in living organisms. Therefore, the role of SIRT-1 in regulating forkhead box O/poly ADP-ribose polymerase-1 (FOXO-1/PARP-1) signaling could provide the necessary validation for developing new pharmacological targets for the promotion or inhibition of SIRT-1 activity toward radiation sensitivity.In the present study, the SIRT-1 signaling pathway is being investigated to study the possible modulatory effect of resveratrol (RSV, SIRT-1 activator) versus nicotinamide (NAM, SIRT-1 inhibitor) in case of liver damage induced by whole-body gamma irradiation. Rats were exposed to 6 Gy gamma radiation after being pretreated with either RSV (10 mg/kg/day) or NAM (100 mg/kg/day) for 5 days, and subsequent examining hepatic morphological changes and apoptotic markers were assessed. The expression of SIRT-1, FOXO-1, and cleaved PARP-1 in the liver was analyzed. RSV improved radiation-induced apoptosis, mitochondrial dysfunction, and inflammation signified by low expression of caspase-3, lactate dehydrogenase, complex-I activity, myeloperoxidase, and total nitric oxide content. RSV increased the expression of SIRT-1, whereas cleaved PARP-1 and FOXO-1 were suppressed. These protective effects were suppressed by inhibition of SIRT-1 activity using NAM. These findings suggest that RSV can attenuate radiation-induced hepatic injury by reducing apoptosis and inflammation via SIRT-1 activity modulation.

No abstract

The aim of the present study is to explore new selective anti-inflammatory compounds with low cardiovascular risk. Twelve thiadiazole derivatives incorporating different amino acid moieties were newly synthesized (4–15) as potential anti-inflammatory agents with low cardiovascular risks through dual COX-2/MPO inhibition. Compounds were initially screened for their anti-inflammatory effect by assay of COX-2, the most potent (4–6, 8) were further tested for COX-1 inhibition, myeloperoxidase MPO activity as well as total nitric oxide content NO in heart of irradiated rats. Cardiac toxicity potential was evaluated by assay of creatine kinase-MB (CK-MB), troponin-I (Tn-I) and lactate dehydrogenase (LDH). Celcoxcib was used as reference drug. S-(5-((4-Methoxybenzylidene)amino)-2,3-dihydro-1,3,4-thiadiazol-2-yl)2-amino propanethioate (5) was the most potent anti-inflammatory with the least cardiotoxicity effect. It exhibited IC50 0.09 µM on COX-2 inhibition with very low activity on COX-1. Troponin I was elevated by 11% using compound 5 in non-irradiated rats. Moreover, compound (5) showed 73% reduction in MPO level. Results were supported by molecular docking into the active sites of COX-2 and MPO enzymes to have more insights about the possible dual inhibition of compound 5 of both enzymes.