Acute and Subchronic Toxicity Study of Methanol Seed Extract of Passion Fruit (Passiflora edulis var. flavicarpa) in Albino Rats

The present study investigates the toxicological properties of the methanol seed extract of Passiflora edulis var. flavicarpa. For the acute toxicity study, a limit test dose of 5000mg/kg was used while in the sub-chronic toxicity study, the treatment groups received a daily oral dose of the extract at 1000, 2000 and 3000 mg/kg for 28 days. The acute toxicity study revealed that the extract was safe up to 5000mg/kg. Results of sub-chronic toxicity study revealed significant (p<0.05) increase in body weight at the dose of 3000mg/kg. Neutrophils in all the treatment groups were significantly increased (p<0.05) while all the other haematological parameters tested showed no significant difference with the control group. The extract also showed mild to moderate deleterious effects on some biochemical parameters. ALT, ALP. AST and GGT levels were significantly increased (p<0.05) with mild distortion of hepatic architecture in the liver of the group that received the highest dose (3000mg/kg).  No pathological changes in the kidneys were observed at the various doses. This suggests that the extract should be used with caution with increasing dose. Keywords: Passiflora edulis var. flavicarpa, acute toxicity study, sub-chronic toxicity study, haematological parameters, biochemical parameters

Antioxidant Activity and Inhibitory Effect of Some Commonly used Medicinal Plants against Lipid Per-Oxidation in Mice Brain

Background: The present study compares the protective properties of aqueous extracts of six medicinal plants, Phyllanthus emblica, Terminaliachebula (black and yellow), Terminalia arjuna, Balsamodendron Mukul and Alium sativum against lipid per-oxidation in mice brain.Methods: The antioxidant activities were analyzed by lipid per-oxidation assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay, total antioxidantactivity and metal chelation.Results: The extracts (fruits and bark) showed inhibition against thiobarbituric acid reactive species (TBARS) induced by pro-oxidant (10 µM FeSO4) in mice brain. Moreover, the free radical scavenging activities of the extracts was evaluated by the scavenging of DPPH radical (IC50, 23.23±1.2 µg/ml (Phyllanthus emblica), 20.24±0.9 µg/ml (Terminalia chebula yellow) and 17.33±1.1 µg/ml (Terminalia chebula black), 19.44±0.45 µg/ml (Terminalia arjuna), 56.59±2.1 µg/ml (Balsamodendron Mukul) and . 200 µg/ml (Alium sativum).Conclusion: The higher antioxidant and inhibitory effect of Terminalia chebula black in this study could be attributed to its significantly higherphenolic content, Fe(II) chelating ability, reducing ability and free radical scavenging activity. Therefore oxidative stress in brain could be potentiallyprevented by the intake of these plants.Key words: Antioxidant activity, Balb c mice, iron chelation, phenolics, oxidative stress, medicinal plants

Influence of autozygosity on common disease risk across the phenotypic spectrum.

Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (FROH) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of FROH. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between FROH and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity

Analysis of transcriptional response to heat stress in Rhazya stricta

Clusters of assembled transcripts of R. stricta SRA in mature leaves (A5-L8) at different time points of the day (A, morning; F-H, midday & L, dusk). Grey lines indicate expression patterns of individual transcripts in a given cluster. Blue lines indicate overall expression pattern across different transcripts of a given cluster. (PDF 397 kb

Adverse psychosocial working conditions and minor psychiatric disorders among bank workers

<p>Abstract</p> <p>Background</p> <p>In most countries, the financial service sector has undergone great organizational changes in the past decades, with potential negative impact on bank workers' mental health. The aim of this paper is to estimate the prevalence of minor psychiatric disorders (MPD) among Brazilian bank workers and to investigate whether they are associated with an adverse psychosocial working environment.</p> <p>Methods</p> <p>A cross-sectional study of a random sample of 2,500 workers in a Brazilian state bank in 2008. The presence of MPD was determined by the General Health Questionnaire.(GHQ). Psychosocial work conditions were assessed by means of the Effort-Reward Imbalance (ERI) and Job Content Questionnaire (JCQ). The presence and magnitude of the independent associations between MPD and adverse psychosocial working conditions were determined by Prevalence Ratios, obtained by Poisson regression.</p> <p>Results</p> <p>From 2,337 eligible workers, 88% participated. The prevalence of MPD was greater among women (45% vs. 41%; p > 0.05). In the multivariate analysis, the prevalence of MPD was twice as high among bank workers exposed to high psychological demand and low control at work and under high effort and low reward working conditions. The lack of social support at work and the presence of over-commitment were also associated with higher prevalence of MPD. A negative interaction effect was found between over-commitment and effort-reward imbalance.</p> <p>Conclusion</p> <p>The prevalence of MPD is high among bank workers. The results reinforce the association between MPD and adverse psychosocial working conditions, assessed by the JCQ and ERI models. The direction of the interaction observed between over-commitment and ERI was contrary to what was expected.</p

Effect of propolis gel on the in vitro reduction of dentin permeability

OBJECTIVE: The aim of this study was to evaluate the capacity of potassium oxalate, fluoride gel and two kinds of propolis gel to reduce the hydraulic conductance of dentin, in vitro. MATERIAL AND METHODS: The methodology used for the measurement of hydraulic conductance of dentin in the present study was based on a model proposed in literature. Thirty-six 1-mm-thick dentin discs, obtained from extracted human third molars were divided into 4 groups (n=9). The groups corresponded to the following experimental materials: GI-10% propolis gel, pH 4.1; GII-30% propolis gel; GIII-3% potassium oxalate gel, pH 4,1; and GIV-1.23% fluoride gel, pH 4.1, applied to the dentin under the following surface conditions: after 37% phosphoric acid and before 6% citric acid application. The occluding capacity of the dentin tubules was evaluated using scanning electron microscopy (SEM) at ×500, ×1,000 and ×2,000 magnifications. Data were analyzed statistically by two-way ANOVA and Tukey's test at 5% significance level. RESULTS: Groups I, II, III, IV did not differ significantly from the others in any conditions by reducing in hydraulic conductance. The active agents reduced dentin permeability; however they produced the smallest reduction in hydraulic conductance when compared to the presence of smear layer (P<0.05). The effectiveness in reducing dentin permeability did not differ significantly from 10% or 30% propolis gels. SEM micrographs revealed that dentin tubules were partially occluded after treatment with propolis. CONCLUSIONS: Under the conditions of this study, the application of 10% and 30% propolis gels did not seem to reduce the hydraulic conductance of dentin in vitro, but it showed capacity of partially obliterating the dentin tubules. Propolis is used in the treatment of different oral problems without causing significant great collateral effects, and can be a good option in the treatment of patients with dentin sensitivity

Effect of mineral-enriched diet and medicinal herbs on Fe, Mn, Zn, and Cu uptake in chicken

<p>Abstract</p> <p>Background</p> <p>The goal of our study was to evaluate the effects of different medicinal herbs rich in polyphenol (Lemon balm, Sage, St. John's wort and Small-flowered Willowherb) used as dietary supplements on bioaccumulation of some essential metals (Fe, Mn, Zn and Cu) in different chicken meats (liver, legs and breast).</p> <p>Results</p> <p>In different type of chicken meats (liver, legs and breast) from chickens fed with diets enriched in minerals and medicinal herbs, beneficial metals (Fe, Mn, Zn and Cu) were analysed by flame atomic absorption spectrometry. Fe is the predominant metal in liver and Zn is the predominant metal in legs and breast chicken meats. The addition of metal salts in the feed influences the accumulations of all metals in the liver, legs and breast chicken meat with specific difference to the type of metal and meat. The greatest influences were observed in legs meat for Fe and Mn. Under the influence of polyphenol-rich medicinal herbs, accumulation of metals in the liver, legs and breast chicken meat presents specific differences for each medicinal herb, to the control group that received a diet supplemented with metal salts only. Great influence on all metal accumulation factors was observed in diet enriched with sage, which had significantly positive effect for all type of chicken meats.</p> <p>Conclusions</p> <p>Under the influence of medicinal herbs rich in different type of polyphenol, accumulation of metals in the liver, legs and breast chicken meat presents significant differences from the group that received a diet supplemented only with metal salts. Each medicinal herb from diet had a specific influence on the accumulation of metals and generally moderate or poor correlations were observed between total phenols and accumulation of metals. This may be due to antagonism between metal ions and presence of other chelating agents (amino acids and protein) from feeding diets which can act as competitor for complexation of metals and influence accumulation of metals in chicken meat.</p> <p><b>Graphical abstract</b></p

Multistep Ion Channel Remodeling and Lethal Arrhythmia Precede Heart Failure in a Mouse Model of Inherited Dilated Cardiomyopathy

Background: Patients with inherited dilated cardiomyopathy (DCM) frequently die with severe heart failure (HF) or die suddenly with arrhythmias, although these symptoms are not always observed at birth. It remains unclear how and when HF and arrhythmogenic changes develop in these DCM mutation carriers. In order to address this issue, properties of the myocardium and underlying gene expressions were studied using a knock-in mouse model of human inherited DCM caused by a deletion mutation DK210 in cardiac troponinT. Methodology/Principal Findings: By 1 month, DCM mice had already enlarged hearts, but showed no symptoms of HF and a much lower mortality than at 2 months or later. At around 2 months, some would die suddenly with no clear symptoms of HF, whereas at 3 months, many of the survivors showed evident symptoms of HF. In isolated left ventricular myocardium (LV) from 2 month-mice, spontaneous activity frequently occurred and action potential duration (APD) was prolonged. Transient outward (Ito) and ultrarapid delayed rectifier K + (IKur) currents were significantly reduced in DCM myocytes. Correspondingly, down-regulation of Kv4.2, Kv1.5 and KChIP2 was evident in mRNA and protein levels. In LVs at 3-months, more frequent spontaneous activity, greater prolongation of APD and further down-regulation in above K + channels were observed. At 1 month, in contrast, infrequent spontaneous activity and down-regulation of Kv4.2, but not Kv1.5 or KChIP2, were observed

Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

<p>Abstract</p> <p>Background</p> <p>Growth hormone (GH) is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy) could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD) and explored the underlying molecular mechanisms.</p> <p>Methods</p> <p>Male C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW) adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism.</p> <p>Results</p> <p>Serum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; <it>P </it>< 0.001). GH1 therapy reversed HMW adiponectin levels to the normal levels in the alcohol-fed group. Alcohol feeding significantly reduced hepatic adipoR2 mRNA expression compared with that in the control group (0.71 ± 0.17 vs. 1.03 ± 0.19; <it>P </it>< 0.001), which was reversed by GH therapy. GH1 therapy also significantly increased the relative mRNA (1.98 ± 0.15 vs. 0.98 ± 0.15) and protein levels of SIRT1 (2.18 ± 0.37 vs. 0.99 ± 0.17) in the alcohol-fed group compared with those in the control group (both, <it>P </it>< 0.001). The alcohol diet decreased the phosphorylated and total protein levels of hepatic AMP-activated kinase-α (AMPKα) (phosphorylated protein: 0.40 ± 0.14 vs. 1.00 ± 0.12; total protein: 0.32 ± 0.12 vs. 1.00 ± 0.14; both, <it>P </it>< 0.001) and peroxisome proliferator activated receptor-α (PPARα) (phosphorylated protein: 0.30 ± 0.09 vs. 1.00 ± 0.09; total protein: 0.27 ± 0.10 vs. 1.00 ± 0.13; both, <it>P </it>< 0.001), which were restored by GH1 therapy. GH therapy also decreased the severity of fatty liver in alcohol-fed mice.</p> <p>Conclusions</p> <p>GH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.</p

Antimetastatic Effects of Phyllanthus on Human Lung (A549) and Breast (MCF-7) Cancer Cell Lines

BACKGROUND: Current chemotherapeutic drugs kill cancer cells mainly by inducing apoptosis. However, they become ineffective once cancer cell has the ability to metastasize, hence the poor prognosis and high mortality rate. Therefore, the purpose of this study was to evaluate the antimetastatic potential of Phyllanthus (P. niruri, P. urinaria, P. watsonii, and P. amarus) on lung and breast carcinoma cells. METHODOLOGY/PRINCIPAL FINDINGS: Cytotoxicity of Phyllanthus plant extracts were first screened using the MTS reduction assay. They were shown to inhibit MCF-7 (breast carcinoma) and A549 (lung carcinoma) cells growth with IC(50) values ranging from 50-180 µg/ml and 65-470 µg/ml for methanolic and aqueous extracts respectively. In comparison, they have lower toxicity on normal cells with the cell viability percentage remaining above 50% when treated up to 1000 µg/ml for both extracts. After determining the non-toxic effective dose, several antimetastasis assays were carried out and Phyllanthus extracts were shown to effectively reduce invasion, migration, and adhesion of both MCF-7 and A549 cells in a dose-dependent manner, at concentrations ranging from 20-200 µg/ml for methanolic extracts and 50-500 µg/ml for aqueous extracts. This was followed by an evaluation of the possible modes of cell death that occurred along with the antimetastatic activity. Phyllanthus was shown to be capable of inducing apoptosis in conjunction with its antimetastastic action, with more than three fold increase of caspases-3 and -7, the presence of DNA-fragmentation and TUNEL-positive cells. The ability of Phyllanthus to exert antimetastatic activities is mostly associated to the presence of polyphenol compounds in its extracts. CONCLUSIONS/SIGNIFICANCE: The presence of polyphenol compounds in the Phyllanthus plant is critically important in the inhibition of the invasion, migration, and adhesion of cancer cells, along with the involvement of apoptosis induction. Hence, Phyllanthus could be a valuable candidate in the treatment of metastatic cancers