Anti-fibrotic effects of curcumin and some of its analogues in the heart.

Cardiac fibrosis stems from the changes in the expression of fibrotic genes in cardiac fibroblasts (CFs) in response to the tissue damage induced by various cardiovascular diseases (CVDs) leading to their transformation into active myofibroblasts, which produce high amounts of extracellular matrix (ECM) proteins leading, in turn, to excessive deposition of ECM in cardiac tissue. The excessive accumulation of ECM elements causes heart stiffness, tissue scarring, electrical conduction disruption and finally cardiac dysfunction and heart failure. Curcumin (Cur; also known as diferuloylmethane) is a polyphenol compound extracted from rhizomes of Curcuma longa with an influence on an extensive spectrum of biological phenomena including cell proliferation, differentiation, inflammation, pathogenesis, chemoprevention, apoptosis, angiogenesis and cardiac pathological changes. Cumulative evidence has suggested a beneficial role for Cur in improving disrupted cardiac function developed by cardiac fibrosis by establishing a balance between degradation and synthesis of ECM components. There are various molecular mechanisms contributing to the development of cardiac fibrosis. We presented a review of Cur effects on cardiac fibrosis and the discovered underlying mechanisms by them Cur interact to establish its cardio-protective effects

Expression of Recombinant Protein B Subunit Pili from Vibrio Cholera

Abstract: Background & Aims: Vibrio cholerae is a gram-negative bacterial pathogen that causes cholera disease. Following ingestion by a host and entry into the upper intestine, V. cholera colonizes and begins to emit enterotoxin. One of the most pathogenic factors of Vibrio cholera is toxin-coregulated pili (TCP). Toxin-Coregulated pili is as the primary factor requiered for the colonization and insistence of bacteria in the small intestine. The toxin-coregulated pili are bundle-forming pili that are coordinately regulated with cholerae toxin (CT). The CT operon is part of the genome of the cholera toxin bacteriophage (CTXQ) which utilizes TCP as its receptor. The aim of this study is to produce a recombinant vaccine for V. cholerae in the future. Methods: The tcpB gene was amplified by Polymerase chain reaction (PCR) method and subcloned into pET32a expression vector. Escherichia coli BL21 (DE3) plysS competent cells were transformed by pET32a - tcpB recombinant plasmid. In different media with changing the parameters of nutrient content like glucose as carbon source and yeast extract as nitrogen source, protein expression was induced by using IPTG. Recombinant protein were purified by affinity chromatography (Ni-NTA). The concentration of Recombinant proteins measured according to Bradford assay. Results: The sequencing results by Sanger method showed a similar sequence as tcpB gene. Escherichia coli BL21 plysS was transformed with TCPB-pET32a and gene expression was induced by IPTG. The expressed protein was purified by affinity chromatography and Ni-NTA kit. Conclusion: Recombinant protein tcpB was produced in the cytoplasm of Escherichia coli BL21 plysS, by pET32a expression vector. Therefore, utilization of this protein in Escherichia coli BL21 plysS by expression vectors such as pET32a is possible

Recombinant toxin-coregulated pilus A (TcpA) as a candidate subunit cholera vaccine

BACKGROUND AND OBJECTIVES: The toxin co-regulated pilus A (TcpA) has been described as a critical pathogenicity factor of Vibrio cholerae. TcpA is a candidate for making subunit vaccine against cholera. The aim of this study was to produce a candidate vaccine by expressing recombinant TcpA in E. coli. MATERIALS AND METHODS: In this study, the toxin co-regulated pilus A gene from EL-Tor, V. cholerae subspecies, was amplified by PCR and sub-cloned into prokaryotic expression vector pGEX4T1. E. coli BL21 (DE3) was transformed with pGEX4T1- TcpA and gene expression was induced by IPTG and purified by GST resin. The integrity of the product was confirmed by Western blot analysis using a standard rabbit anti-V. cholerae antibody. Sera reactivity of infected individuals was further analyzed against the recombinant TcpA protein. RESULTS: The concentration of purified recombinant protein was calculated to be 8 mg/L of initial culture. The integrity of product was confirmed by Western blot analysis using a standard rabbit anti V. cholerae antibody. Sera reactivity of infected individual was further analyzed against the recombinant TcpA protein. The obtained data indicated that recombinant TcpA protein from V. cholerae was recognized by patient serum and animal sera. CONCLUSION: These results show that the recombinant TcpA is antigenic and could be used in a carrier host as an oral vaccine against cholera

Effect of methylphenidate hydrochloride on ovarian and pituitary gonadotropin hormone in peripubertal mice

Background and Objective: Attention deficit hyperactivity disorder (ADHD) is the most common in psychology and Methylphenidate hydrochloride (MPH) is one of the most frequently prescribed pediatric medicine. This study was done to determine the effect of Methylphenidate hydrochloride on ovarian and pituitary gonadotropin hormone in peripubertal mice Materials and Methods: This experimental study was done on 40 preipubertal female mice (BALB/c) with three weeks age and approximate 12-15 gram. The mice were allocated randomly in one control and three experimental groups, designated as I, II and III. Animals in group I, II and III were received by gavage Methylphenidate hydrochloride with 2, 5 and 10 mg/kg body weight for six days, respectively. At the end of experiment body weight, serum estrogen, progesterone and pituitary gonadotropins were measured. Morphometric and histopathological evaluation of ovary were examined. Data were analyzed using SPSS-17, ANOVA and Tukey tests. Results: The body weight and ovary dimensions of animals in experimental groups were reduced significantly in comparison with control (P<0.05). Abnormal cells, structural alternations of granules cells and follicular growth abnormality were observed in experimental groups I and III in compare to control group. A significant reduction of estrogen, in group I, progesterone levels in group I and III were observed in comparison with the controls (P<0.05). Conclusion: This study showed that the Methylphenidate hydrochloride administration induces the reduction of body weight, ovary dimensions and hormones

Statin-induced nitric oxide signalling: mechanisms and therapeutic implications

In addition to their cholesterol-lowering effects, statins are associated with pleiotropic effects including improvements in heart failure (HF), reduced blood pressure, prevention of the rupture of atherosclerotic plaques and improved angiogenesis. In addition to these cardiovascular benefits, statins have been implicated in the treatment of neurological injuries, cancer, sepsis, and cirrhosis. These cholesterol-independent beneficial effects of statins are predominantly mediated through signaling pathways leading to increased production and bioavailability of nitric oxide (NO). In this review, the mechanistic pathways and therapeutic effects of statin-mediated elevations of NO are described and discussed