Sinapic Acid Prevents Hypertension and Cardiovascular Remodeling in Pharmacological Model of Nitric Oxide Inhibited Rats

Objectives

Hypertensive heart disease is a constellation of abnormalities that includes cardiac fibrosis in response to elevated blood pressure, systolic and diastolic dysfunction. The present study was undertaken to examine the effect of sinapic acid on high blood pressure and cardiovascular remodeling.

Methods

An experimental hypertensive animal model was induced by L-NAME intake on rats. Sinapic acid (SA) was orally administered at a dose of 10, 20 and 40 mg/kg body weight (b.w.). Blood pressure was measured by tail cuff plethysmography system. Cardiac and vascular function was evaluated by Langendorff isolated heart system and organ bath studies, respectively. Fibrotic remodeling of heart and aorta was assessed by histopathologic analyses. Oxidative stress was measured by biochemical assays. mRNA and protein expressions were assessed by RT-qPCR and western blot, respectively. In order to confirm the protective role of SA on endothelial cells through its antioxidant property, we have utilized the in vitro model of H₂O₂-induced oxidative stress in EA.hy926 endothelial cells.

Results

Rats with hypertension showed elevated blood pressure, declined myocardial performance associated with myocardial hypertrophy and fibrosis, diminished vascular response, nitric oxide (NO) metabolites level, elevated markers of oxidative stress (TBARS, LOOH), ACE activity, depleted antioxidant system (SOD, CAT, GPx, reduced GSH), aberrant expression of TGF-β, β-MHC, eNOS mRNAs and eNOS protein. Remarkably, SA attenuated high blood pressure, myocardial, vascular dysfunction, cardiac fibrosis, oxidative stress and ACE activity. Level of NO metabolites, antioxidant system, and altered gene expression were also repaired by SA treatment. Results of in vitro study showed that, SA protects endothelial cells from oxidative stress and enhance the production of NO in a concentration dependent manner.

Conclusions

Taken together, these results suggest that SA may have beneficial role in the treatment of hypertensive heart disease by attenuating fibrosis and oxidative stress through its antioxidant potential.     

Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target

Heat shock proteins (HSP) are highly conserved across eukaryotic and prokaryotic species. These proteins play a role in response to cellular stressors, protecting cells from damage and facilitating recovery. In tumor cells, HSPs can have cytoprotective effects and interfere with apoptotic cascades. This study was performed to assess the prognostic and predictive values of the gene expression of HSP family members in canine osteosarcoma (OS) and their potential for targeted therapy. Gene expressions for HSP were assessed using quantitative PCR (qPCR) on 58 snap-frozen primary canine OS tumors and related to clinic-pathological parameters. A significant increased expression of HSP60 was found in relation to shorter overall survival and an osteoblastic phenotype. Therefore, the function of HSP60 was investigated in more detail. Immunohistochemical analysis revealed heterogeneous staining for HSP60 in tumors. The highest immunoreactivity was found in tumors of short surviving dogs. Next HSP expression was shown in a variety of canine and human OS cell lines by qPCR and Western blot. In two highly metastatic cell lines HSP60 expression was silenced using siRNA resulting in decreased cell proliferation and induction of apoptosis in both cell lines. It is concluded that overexpression of HSP60 is associated with a poor prognosis of OS and should be evaluated as a new target for therapy.     

Mitochondrial dysfunction mediated apoptosis of HT-29 cells through CS-PAC-AgNPs and investigation of genotoxic effects in zebra (Danio rerio) fish model for drug delivery

The present study reports the validation of cancer nanotherapy using proanthocyanidin (PAC). Nowadays, in vitro and in vivo deliveries of nanoparticle (NPs) drugs have been paid more attention, intensively. Moreover, the current chemotherapeutic drugs have few first rate drawbacks including lack of specificity and requirement of excessive drug doses. To overcome this problem of chemotherapy, the attainment of high drug loading in combination with degradable polymer nanoparticles (for instance,chitosan) is a trending research in cancer biology. Hence, in this study, the synthesized PAC-AgNPs were successfully crosslinked with chitosan nanoparticles (CS-PAC-AgNPs), which were found to be spherical or polygonal in shape with a median size of 70.68 nm and 52.16 nm as observed by FTIR, FESEM and TEM analysis; thus, being suitable for drug delivery. CS-PAC-AgNPs were taken up via endocytosis by cancer cells and enabled the release cytochrome-C from mitochondria, followed by dysregulation of anti-apoptotic protein Bcl2 family, inducing the apoptotic mediated activation of caspase 9 and 3. To identify the genotoxicity of the synthesized CS-PAC-AgNPs, the mortality, hatching rate, malformation and abnormalities of embryo/larvae of the vertebrate zebra fish model (Danio rerio) were observed in a dose-time-dependent manner. This improved cancer nanotherapy can thus be utilized as a novel nanocombination for inducing apoptosis in vitro and in vivo.     

Colorimetric detection of in situ metal acetates and fluorides by a bipyridyl‐linked Schiff base

Here, we present a new bipyridyl moiety linked Schiff base (bipy‐1) that is well characterized using spectroscopic techniques. Colorimetric and UV‐vis titrations were used to study the photophysical properties of bipy‐1 in the presence of various tetrabutyl ammonium salt of anions and metal salts containing different counter cations. bipy‐1 showed selective recognition of dimethyl sulphoxide solution of tetrabutyl ammonium salt of F^? ion accompanied with a UV‐vis band at 529 nm and interesting binding of aqueous Co, Ni, and Cu acetates/fluorides, as confirmed by distinct color changes from fluorescent green to pink or orange and a strong band around 480–510 nm in the UV‐vis spectrum. However, in the presence of Co, Ni, and Cu countercations, any form of metal acetate/fluorides was found to be able to respond to similar color changes from fluorescent green to pink or orange, showing a band around 480–510 nm. This type of output clearly indicates that the in situ formation of Co, Ni, and Cu acetates/fluorides also coordinates with bipyridyl nitrogen atoms. Copyright © 2014 John Wiley & Sons, Ltd.     

Pre-Dialysis Systolic Blood Pressure-Variability Is Independently Associated with All-Cause Mortality in Incident Haemodialysis Patients

Systolic blood pressure variability is an independent risk factor for mortality and cardiovascular events. Standard measures of blood pressure predict outcome poorly in haemodialysis patients. We investigated whether systolic blood pressure variability was associated with mortality in incident haemodialysis patients. We performed a longitudinal observational study of patients commencing haemodialysis between 2005 and 2011 in East Anglia, UK, excluding patients with cardiovascular events within 6 months of starting haemodialysis. The main exposure was variability independent of the mean (VIM) of systolic blood pressure from short-gap, pre-dialysis blood pressure readings between 3 and 6 months after commencing haemodialysis, and the outcome was all-cause mortality. Of 203 patients, 37 (18.2%) patients died during a mean follow-up of 2.0 (SD 1.3) years. The age and sex-adjusted hazard ratio (HR) for mortality was 1.09 (95% confidence interval (CI) 1.02–1.17) for a one-unit increase of VIM. This was not altered by adjustment for diabetes, prior cardiovascular disease and mean systolic blood pressure (HR 1.09, 95% CI 1.02–1.16). Patients with VIM of systolic blood pressure above the median were 2.4 (95% CI 1.17–4.74) times more likely to die during follow-up than those below the median. Results were similar for all measures of blood pressure variability and further adjustment for type of dialysis access, use of antihypertensives and absolute or variability of fluid intake did not alter these findings. Diastolic blood pressure variability showed no association with all cause mortality. Our study shows that variability of systolic blood pressure is a strong and independent predictor of all-cause mortality in incident haemodialysis patients. Further research is needed to understand the mechanism as this may form a therapeutic target or focus for management.     

Development of new formulations of Bacillus subtilis for management of tomato damping-off caused by Pythium aphanidermatum

Formulations of a strain of Bacillus subtilis AUBS-1 inhibitory to the growth of the damping-off pathogen, Pythium aphanidermatum, were developed for seed treatment. The formulations included a talc-based powder, lignite-based powder, lignite+fly ash-based powder, wettable powder, bentonite-paste, polyethylene glycol (PEG) paste and a water-dispersible tablet. Formulations were stored at room temperature for 2 years and frequently sampled to test their shelf life. Populations of bacteria in the formulations were stable for up to 2 years storage at room temperature (28°C). Viability of propagules in lignite, lignite+fly ash, bentonite paste, wettable powder and water dispersible tablet formulations was 100% for up to 1 year. However, the viability of propagules was significantly reduced in talc, wettable powder, PEG paste and tablet formulations beyond 1 year of storage. Seed treatment of tomato with these formulations resulted in effective control of damping-off caused by P. aphanidermatum, and also enhanced plant biomass under glasshouse and field conditions. Active rhizosphere colonization by the bacterium was observed on tomato plants grown from seeds treated with the above formulations.     

Assessment of bacterial community composition in response to uranium levels in sediment samples of sacred Cauvery River

Applied Microbiology and Biotechnology - Global industrialization is a major cause of effluent discharge from industries up to alarming concentrations. Especially, uranium concentrations in water...