Green synthesis of copper oxide nanoparticles using sinapic acid: an underpinning step towards antiangiogenic therapy for breast cancer.

Synthesis of copper oxide nanoparticles without any chemical reductant is always a challenging methodology for biological studies. In this study, sinapic acid, a phytochemical, is used for the synthesis of stable copper oxide nanoparticles. The as-synthesized nanoparticles were characterized thoroughly using UV-Visible, IR spectroscopy, Transmission Electron Microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Nanoparticles collected during different time intervals of synthesis (60,120 and 180 min) were subjected for analysis, where the occurrence of copper oxide nanoparticles with substantial morphology was seen at 180 min. Further, nanoparticles synthesized at 120 and 180 min were studied for their potential biological applications. These copper oxide nanoparticles evinced potential cytotoxic effects on breast cancer cells, MCF7 and MDA-MB231. Supplementarily, it also exhibited anti-angiogenic effect on endothelial cells (EA.hy926), thus confirming its potential to inhibit angiogenesis in cancer.

Gymnema montanum improves endothelial function via inhibition of endoplasmic reticulum stress by activating Nrf2 signaling

Objective: To investigate the effects of Gymnema montanum leaf extract against endoplasmic reticulum (ER) stress-induced toxicity in endothelial cells. Methods: The immortalized endothelial hybrid cell, EA.hy926 was treated with different concentrations of Gymnema montanum leaf extract (0-100 μg/mL) and the ER stress inducer, tunicamycin. The cytotoxicity was assessed by MTT as well as lactate dehydrogenase and malondialdehyde levels were determined. The levels of ER stress markers, GRP78 and CHOP were analysed by Western blot assay. The Gymnema montanum leaf extract-mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) was assessed by cell-based luciferase enzyme fragment complementation assay and antioxidant responsive element driven luciferase reporter assay. The levels of phosphoproteins of the MAPK pathway were analyzed using the Bioplex system. Results: A dose-dependent cytoprotective effect of Gymnema montanum leaf extract was observed in tunicamycin-induced toxicity. Gymnema montanum leaf extract significantly reduced lactate dehydrogenase activity and malondialdehyde levels in ER stress-induced endothelial cells. It also suppressed ER stress markers dose dependently and inhibited the phosphorylation of JNK, ERK, MEK and p38 MAPK in tunicamycin-induced endothelial cells. Moreover, Gymnema montanum leaf extract increased the expression of Nrf2 and its downstream targets in endothelial cells. Conclusions: Gymnema montanum leaf extract attenuates ER stress by increasing the expression of Nrf2 and its downstream genes.

Effect of simulated microgravity on E. coli K12 MG1655 growth and gene expression.

This study demonstrates the effects of simulated microgravity on E. coli K 12 MG1655 grown on LB medium supplemented with glycerol. Global gene expression analysis indicated that the expressions of hundred genes were significantly altered in simulated microgravity conditions compared to that of normal gravity conditions. Under these conditions genes coding for adaptation to stress are up regulated (sufE and ssrA) and simultaneously genes coding for membrane transporters (ompC, exbB, actP, mgtA, cysW and nikB) and carbohydrate catabolic processes (ldcC, ptsA, rhaD and rhaS) are down regulated. The enhanced growth in simulated gravity conditions may be because of the adequate supply of energy/reducing equivalents and up regulation of genes involved in DNA replication (srmB) and repression of the genes encoding for nucleoside metabolism (dfp, pyrD and spoT). In addition, E. coli cultured in LB medium supplemented with glycerol (so as to protect the cells from freezing temperatures) do not exhibit multiple stress responses that are normally observed when cells are exposed to microgravity in LB medium without glycerol.

Allele, genotype and haplotype structures of functional polymorphic variants in endothelial nitric oxide synthase [eNOS], angiotensinogen [ACE] and aldosterone synthase [CYP11B2] genes in healthy pregnant women of Indian ethnicity

Variants in the candidate genes eNOS, CYP11B2 and ACE have been implicated as liable biomarkers that can predict complications like hypertension and preeclampsia. Studies on the impact and distribution of these variants on healthy pregnancy have not been done so far in south Indian or in any of the native Indian population. Examining these variants could lay a strong basis in understanding the genetic aspects of preeclampsia and further offer effective means in early risk assessment in a preeclampsia. Genotyping for 303 unrelated healthy women of Tamilian origin who underwent uncomplicated term pregnancies was executed by PCR-RFLP for eNOS, CYP11B2 and ACE variants. Haplotype assessment and pairwise linkage disequilibrium [LD] investigation were performed by Haploview software. The prevalence of eNOS variants [-786T>C, Glu298Asp and intron 4 VNTR] was 12%, 21.6% and 21.1%, respectively. The incidence of CYP11B2 [-344 C>T] and ACE [287 bp Alu I/D] variants was found to be 43.8% and 42.7%. The observed frequencies of the studied polymorphisms did not diverge from the HWE [p>0.05]. Significant LD was observed between 3 eNOS gene polymorphisms. Six different haplotype structures with a frequency of >1% were generated from three eNOS variants. Among the haplotypes generated, the haplotype T-4b-G was the most common with the frequency of 64.4%. There was a statistically significant inconsistency in the study population in comparison to other global races. The outcome of this study could be used for investigating future therapeutic value of the variants in a preeclamptic set-up which could pose a credible diagnostic potential for primary risk assessment of women susceptible to preeclampsia/ other pregnancy related complications