Sirtuin3 in Neurological Disorders.

Sirtuins are NAD+ dependent enzymes that have a predominant role in neurodegenerative disorders and also regulate the inflammatory process, protein aggregation, etc. The relationships between sirtuins with that of the nervous system and neurodegeneration, are widely studied. Sirtuins have a strong role in metabolic syndrome in mitochondria also. The activities of sirtuins can be altered by using small molecules that would be developed into drugs and it is proven that the manipulation of SIRT1 activity influences neurodegenerative disease models. They are interesting since using small molecules, which would be developed into a drug, it is feasible to alter the activities of sirtuins. Different functions of sirtuins depend upon their subcellular localization. In this review paper, we discuss different sirtuins, differential expression of sirtuins, and expression of sirtuin in the brain and briefly explains Sirtuin3 (SIRT3).

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review.

Recent investigations suggest that gut microbiota affects the brain activity through the microbiota-gut-brain axis under both physiological and pathological disease conditions like Parkinson's disease. Further dopamine synthesis in the brain is induced by dopamine producing enzymes that are controlled by gut microbiota via the microbiota-gut-brain axis. Also alpha synuclein deposition and the associated neurodegeneration in the enteric nervous system that increase intestinal permeability, oxidative stress, and local inflammation, accounts for constipation in Parkinson's disease patients. The trigger that causes blood brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the central nervous system is believed to be due to the chronic low-grade inflammation in the gut. The non-motor symptoms that appear years before motor symptoms could be reliable early biomarkers, if they could be correlated with the established and reliable neuroimaging techniques or behavioral indices. The future directions should therefore, focus on the exploration of newer investigational techniques to identify these reliable early biomarkers and define the specific gut microbes that contribute to the development of Parkinson's disease. This ultimately should pave the way to safer and novel therapeutic approaches that avoid the complications of the drugs delivered today to the brain of Parkinson's disease patients.

Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy.

Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. © 2016 BioFactors, 43(2):187-194, 2017.

Synthesis and biological evaluation of some schiff bases of [4-(amino)-5-phenyl-4H-1, 2,4-triazole-3-thiol].

The basic nucleus 4-(amino)-5-phenyl-l-4H-1,2,4-triazole-3-thiol was prepared by cyclisation of potassium dithiocarbazinate with hydrazine hydrate using water as solvent under reflux condition for 3-4 h. The compound which has been synthesized successfully was subjected to addition reaction with different aldehydes to synthesize Schiff bases. The compounds were confirmed by physical parameters (solubility, melting point), chromatographic methods (TLC) and at last spectroscopic methods (IR, NMR, and Mass). In order to ascertain the pharmaceutical application, the selective pharmacological screening of the derivatives was carried out according to the standard procedures. The compounds were screened for their antianxietic activity by elevated plus maze method, antidepressant activity by forced swim test. Among the synthesized compounds, the Schiff bases of benzaldehyde (5e), furfuraldehyde (5d) and 2,4-dichloro benzaldehyde (5a) showed extremely significant activities. Results indicate that these compounds may be potential candidates for managing CNS disorders. However further studies are required to substantiate the same which are underway in our lab.