University of Madras

About: University of Madras is a education organization based out in Chennai, Tamil Nadu, India. It is known for research contribution in the topics: Ring (chemistry) & Lipid peroxidation. The organization has 8496 authors who have published 11369 publications receiving 211152 citations. The organization is also known as: Madras University & University of Chennai.

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

Abstract: In a study of 530 individuals with non-syndromic, sensorineural hearing loss, we identified 18 mutations at connexin 26 (Cx26), four of which are novel (-23G>T, I33T, 377_383dupTCCGCAT, W172R) and the remaining 14 (ivs1+1G>A, M1V, 35delG, W24X, I35S, V37I, R75W, W77X, 312del14, E120del, Q124X, Y136X, R143W, R184P) being mutations previously described. To gain insight into functional consequences of these mutations, cellular localization of the mutant proteins and their ability to permit lucifer yellow transfer between cells was studied in seven of them (W24X, I33T, I35S, R75W, E120del, W172R and R184P). I35S and R184P showed impaired trafficking of the protein to the plasma membrane. I33T, R75W, E120del and W172R showed predominantly membrane localization but did not form functional gap junction channels. Surprisingly, W24X, a protein-truncating mutation, apparently permits formation of a full-length protein, perhaps due to a stop codon read-through mechanism. These results provide further evidence that Cx26 mutations affect gap junction activity by mis-regulation at multiple levels.

Berberine inhibits Smad and non-Smad signaling cascades and enhances autophagy against pulmonary fibrosis.

Abstract: Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disorder of unknown aetiology. Transforming growth factor-β1 (TGF-β1)-mediated Smad and non-Smad signaling cascades are considered as central players in accelerating pulmonary fibrosis. We earlier reported berberine’s amelioration against TGF-β1-mediated pro-fibrotic effects in bleomycin-induced pulmonary fibrosis. The present study aimed to determine the regulatory role of berberine on abrogated Smad 2/3 and FAK-dependent PI3K/Akt-mTOR signaling cascades in bleomycin-induced pulmonary fibrosis. Male Wistar rats were subjected to single intratracheal instillation of bleomycin (2.5 U/kg) on day 0, and berberine treatments were provided in either preventive or therapeutic modes, respectively. Berberine mitigated the elevated expression of fibrotic markers, α-smooth muscle actin (α-SMA), fibronectin, collagens I and III and reversed bleomycin-induced ultrastructural alterations in the lungs. Berberine inhibited the bleomycin-induced raise in p-Smad 2/3 and enhanced Smad 7 expression. Berberine blocked the activation of FAK and PI3K/Akt against bleomycin-induced dysregulation, with subsequent raise in PTEN expression. In addition, by inhibiting p-mTOR, berberine stimulated autophagy as evidenced by increase in Beclin-1, LC3-II levels with enhanced autophagosome formation. Cumulatively, through targeted inhibition of dysregulated Smad and FAK-dependent PI3K/Akt-mTOR signaling axis, berberine attenuated the fibrotic insults of bleomycin.

Structural, electrochemical, phosphate-hydrolysis, DNA binding and cleavage studies of new macrocyclic binuclear nickel(II) complexes

Abstract: New macrocyclic binuclear nickel(II) complexes have been synthesized by using the bicompartmental mononuclear complex [NiL] [3,30-((1E,7E)-3,6-dioxa-2,7-diazaocta-1,7-diene-1,8-diyl)bis(3-formyl-5-methyl-2-diolato)nickel(II)] with various diamines like 1,2-bis(aminooxy)ethane (L1), 1,2-diamino ethane (L2), 1,3-diamino propane (L3), 1,4-diamino butane (L4), 1,2-diamino benzene (L5), and 1,8-diamino naphthalene (L6). The complexes were characterized by elemental analysis and spectroscopic methods. The molecular structures of the symmetrical binuclear complex [Ni2L1(H2O)4](ClO4)2 (1) and unsymmetrical binuclear complex [Ni2L3(H2O)4](ClO4)2·(H2O)4 (3) were determined by single-crystal X-ray diffraction. The geometry around both the nickel(II) ions in each molecule is a slightly distorted octahedral. The distance between the Ni⋯Ni centers for complex 1 is 3.039 A and for complex 3 is 3.059 A. The influence of the coordination geometry and the ring size of the binucleating ligands on the electronic, redox, phosphate hydrolysis, DNA binding and cleavage properties have been studied. Electrochemical studies of the complexes show two quasi-reversible one electron reduction processes between −0.49 to −1.69 V. The reduction potential of the binuclear Ni(II) complexes shifts towards anodically upon increasing the macrocyclic ring size. The observed first order rate constant values for the hydrolysis of 4-nitrophenyl phosphate reaction are in the range from 8.69 × 10−3 to 1.85 × 10−2 s−1. The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range from 1.4 × 104 to 17.5 × 104 M−1. The absorption, fluorescence and CD spectral data suggests that the complexes are strongly interacting with DNA. These complexes display hydrolytic cleavage of supercoiled pBR322DNA in the presence of H2O2 at pH 7.2 and 37 °C. The hydrolytic cleavage of DNA by the complexes is supported by the evidence from free radical quenching and T4 ligase ligation. The pseudo-Michaelis–Menten kinetic parameters kcat = 1.27 ± 0.4 h−1 and KM = 7.7 × 10−2 M for naphthalene diimine containing macrocyclic binuclear nickel(II) complex, (6) were obtained.

Gastroprotective effect of Cissus quadrangularis extract in rats with experimentally induced ulcer.

Abstract: Background & objectives: Most of the non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin cause gastric ulcer. In order to study the gastroprotective effect of Cissus quadrangularis extract (CQE), this study was undertaken on aspirin-induc ed ulcerogenesis in pyloric ligated (ASP-PL) model in rats. Results: Pretreatment with CQE significantly prevented the gastric mucosal lesion development and decreased the gastric toxicity produced by ulcerogen. In addition, ulcerated rats showed depletion of gastric wall mucus, glycoproteins and NPSH levels whereas treatment with CQE reverted this decline in ASP-PL induced rats. Histological studies confirmed the results. Interpretation & conclusion: The present finding suggests that CQE promotes ulcer protection by the decrease in ulcer index, gastric secretions and increase in the glycoprotein level, gastric mucin content and NPSH concentration. CQE may protect the gastric mucosa against ulceration by its antisecretory and cytoprotective property.