A meta-analysis of the association of serum ischaemia-modified albumin levels with human hypothyroidism and hyperthyroidism.

Serum levels of ischaemia-modified albumin (IMA) have been studied as a novel and simple measure of oxidative stress (OXS) in different thyroid pathologies. However, results of available studies in the literature were not consistent. This meta-analysis was attempted to quantify the overall effect size for serum IMA levels in human hypothyroidism (HT) and hyperthyroidism (HYT) and to study its associations with the thyroid profile. Databases of PubMed/Medline, EMBASE, Google Scholar, Web of Science and Science Direct were searched for articles. Data on serum IMA levels in HT, HYT patients and euthyroid controls were extracted to compute standardized mean differences (SMD) by the random-effects model. The associations between IMA and thyroid profile were computed by the meta-analysis of correlation coefficients. IMA levels in HT patients (SMD=1.12; Z=2.76; P=0.006) and HYT patients (SMD=1.64; Z=2.57; P=0.01) were significantly higher than in euthyroid controls and the thyroid treatment showed a favourble effect on serum IMA levels. There were strong and significant correlations between IMA and hormonal status in HT and HYT groups. This meta-analysis showing increased IMA level in both HT and HYT patients and its association with thyroid profile suggests that serum IMA could be used as a simple measure of increased OXS in thyroid dysfunction.

Homology modeling, molecular dynamics, and virtual screening of NorA efflux pump inhibitors of Staphylococcus aureus.

Emerging drug resistance in clinical isolates of Staphylococcus aureus might be implicated to the overexpression of NorA efflux pump which is capable of extruding numerous structurally diverse compounds. However, NorA efflux pump is considered as a potential drug target for the development of efflux pump inhibitors. In the present study, NorA model was constructed based on the crystal structure of glycerol-3-phosphate transporter (PDBID: 1PW4). Molecular dynamics (MD) simulation was performed using NAMD2.7 for NorA which is embedded in the hydrated lipid bilayer. Structural design of NorA unveils amino (N)- and carboxyl (C)-terminal domains which are connected by long cytoplasmic loop. N and C domains are composed of six transmembrane α-helices (TM) which exhibits pseudo-twofold symmetry and possess voluminous substrate binding cavity between TM helices. Molecular docking of reserpine, totarol, ferruginol, salvin, thioxanthene, phenothiazine, omeprazole, verapamil, nalidixic acid, ciprofloxacin, levofloxacin, and acridine to NorA found that all the molecules were bound at the large hydrophobic cleft and indicated significant interactions with the key residues. In addition, structure-based virtual screening was employed which indicates that 14 potent novel lead molecules such as CID58685302, CID58685367, CID5799283, CID5578487, CID60028372, ZINC12196383, ZINC72140751, ZINC72137843, ZINC39227983, ZINC43742707, ZINC12196375, ZINC66166948, ZINC39228014, and ZINC14616160 have highest binding affinity for NorA. These lead molecules displayed considerable pharmacological properties as evidenced by Lipinski rule of five and prophecy of toxicity risk assessment. Thus, the present study will be helpful in designing and synthesis of a novel class of NorA efflux pump inhibitors that restore the susceptibilities of drug compounds.

Structure elucidation and antioxidant activity of the phenolic compounds from Rhynchosia suaveolens.

A new benzophenone, 2-hydroxy-3,4-dimethoxybenzophenone (1), together with a known C-glycosylxanthone, mangiferin (2) and two known C-glycosylflavones, isovitexin (3) and isoorientin (4), were isolated from the flowers of Rhynchosia suaveolens DC. (Fabaceae). The structure of the new compound (1) and the known compounds (2-4) were elucidated by extensive 1D and 2D NMR spectral studies. The plant extracts, as well as the isolated compounds, were evaluated for their total phenolic content (TPC), total flavonoid content (TFC) and DPPH radical scavenging activity. Among the isolated compounds, mangiferin (2) and isoorientin (4) showed significant radical scavenging activity comparable with that of ascorbic acid.