Effect of oleic acid supplementation on prostaglandin production in maternal endometrial and fetal allantochorion cells isolated from late gestation ewes

Elevated circulating non-esterified fatty acids including oleic acid (OA) are associated with many pregnancy related complications. Prostaglandins (PGs) play crucial roles during parturition. We investigated the effect of OA supplementation on PG production using an in vitro model of ovine placenta

A rapid and reliable determination of doxycycline hyclate by HPLC with UV detection in pharmaceutical samples

An accurate, sensitive and reproducible high performance liquid chromatographic (HPLC) method for the quantification of doxycycline hyclate in pharmaceutical samples has been developed and validated. The drug and the standard were eluted from a Lichrosorb RP-8 (250 mm´4.6 mm, 10 mm particle size) at 20 °C with a mobile phase consisting of methanol, acetonitrile and 0.010 M aqueous solution of oxalic acid (2:3:5, v/v/v). The flow rate was 1.25 ml min-1. A UV detector set at 350 nm was used to monitor the effluent. Each analysis required no longer than 4 min. The limits of detection and quantification were 1.15 and 3.84 μg ml-1, respectively. Recoveries for different concentrations ranged from 99.58 to 101.93 %

What is the potential of p53 isoforms as a predictive biomarker in the treatment of cancer?

Introduction: For decades, p53 was researched as a single protein with alterations described as mutants. The discovery of 12 human p53 isoforms expressed from 9 transcripts changed this perception, eloquently explaining the numerous roles p53 plays, including apoptosis, senescence, and regeneration. Area covered: Here, we summarise the p53 isoforms and their relevance to cancer to establish an understanding and theorise on potential applications of the isoforms in clinical practice. Expert commentary: Pertaining to the different expression of isoforms in different tumors, it is concluded that the clinical use of isoforms as prognostic and predictive biomarkers will be different depending on the cell type, the tissue origin of the tumors, the position of the TP53 mutation and the driver-oncogene.</p

Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers and shows resistance to any therapeutic strategy used. Here we tested small-molecule inhibitors targeting chromatin regulators as possible therapeutic agents in PDAC. We show that JQ1, an inhibitor of the bromodomain and extraterminal (BET) family of proteins, suppresses PDAC development in mice by inhibiting both MYC activity and inflammatory signals. The histone deacetylase (HDAC) inhibitor SAHA synergizes with JQ1 to augment cell death and more potently suppress advanced PDAC. Finally, using a CRISPR-Cas9–based method for gene editing directly in the mouse adult pancreas, we show that de-repression of p57 (also known as KIP2 or CDKN1C) upon combined BET and HDAC inhibition is required for the induction of combination therapy–induced cell death in PDAC. SAHA is approved for human use, and molecules similar to JQ1 are being tested in clinical trials. Thus, these studies identify a promising epigenetic-based therapeutic strategy that may be rapidly implemented in fatal human tumors

Phenolic Profile and Antioxidant Activity of Pulp and Peel from Peach and Nectarine Fruits

Peach (Prunus persica L.) is a fruit of high nutritional and economic value. Carbohydrates, dietary fibers, minerals and organic acids are among the major constituents of peach fruit, which contribute to the nutritional quality of both fresh fruits and juice. Polyphenolic compounds found in peach may play an important role in physiological functions related to human health. Different polyphenolics may have varied biological activities including antioxidant activity. In this study antioxidant characteristics between peel and pulp of different peach cultivars (‘RadmilovÄanka’, ‘June Gold’, ‘Blake’, ‘Hale’, ‘Vesna’, ‘Adria’) and one of nectarine (‘Fantasia’) were investigated. The peel and pulp extracts showed a huge amount of total phenolics (TP), total flavonoids (TF), total hydroxycinnamates (TH) and total flavonols (TFL), ranging from 42.7-211.4, 11.1-128.5 mg GAE/100 g fresh weight (f.w.) (TP), 21.9 -94.9, 5.0-58.9 mg CE/100 g f.w. (TF), 28.4-389.2, 8.5-165.8 mg kg-1 f.w. (TH) and 17.3-54 mg kg-1 f.w. (TFL). High contents of phenolic compounds were significantly correlated with high antioxidant capacities. Peach pulp and peel differ significantly in their phenolic profiles: the pulp contains mainly chlorogenic, neochlorogenic and p-coumaric acids, whereas the peel possesses chlorogenic, neochlorogenic and p-coumaric acids together with several flavonol glycosides in huge amounts. Our results indicate that cultivar and extraction solvent play important roles in phenolic compositions and antioxidant properties of peach and nectarine extracts, which was shown using statistical analysis (ANOVA). There are high correlations between extracted phenolic compounds and peach and nectarine cultivars, and used solvent and part of the fruit (peel and pulp)

Plasticity of the Muscle Stem Cell Microenvironment

Satellite cells (SCs) are adult muscle stem cells capable of repairing damaged and creating new muscle tissue throughout life. Their functionality is tightly controlled by a microenvironment composed of a wide variety of factors, such as numerous secreted molecules and different cell types, including blood vessels, oxygen, hormones, motor neurons, immune cells, cytokines, fibroblasts, growth factors, myofibers, myofiber metabolism, the extracellular matrix and tissue stiffness. This complex niche controls SC biology-quiescence, activation, proliferation, differentiation or renewal and return to quiescence. In this review, we attempt to give a brief overview of the most important players in the niche and their mutual interaction with SCs. We address the importance of the niche to SC behavior under physiological and pathological conditions, and finally survey the significance of an artificial niche both for basic and translational research purposes

Integrity and life estimation of turbine runner cover in a hydro power plant

This paper presents integrity and life estimation of turbine runner cover in a vertical pipe turbines,Kaplan 200 MW nominal output power, produced in Russia, and built in six hydro-generation units ofhydroelectric power plant „Đerdap 1” in Serbia. Fatigue and corrosion-fatigue interaction have been taken intoaccount using experimentally obtained material properties, as well as analytical and numerical calculations ofstress state, to estimate appropriate safety factors. Fatigue crack growth rate, da/dN, was also calculated,indicated that internal defects of circular or elliptical shape, found out by ultrasonic testing, do not affect reliableoperation of runner cover

Selected derivatives of erythromycin B- in silico and anti-malarial studies

Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their in silico molecular docking into segments of the exit tunnel of the apicoplast ribosome from Plasmodium falciparum. This is believed to be the target of the erythromycin A derivative, azithromycin, which has mild anti-malarial activity. The erythromycin B derivatives were evaluated on the multi-drug (chloroquine, pyrimethamine, and sulfadoxine)-resistant strain K1 of P. falciparum for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of P. falciparum with low micro-molar IC50 values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC50 of 68.6 µM, d-erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of P. falciparum. Based on the molecular docking, it seems that a small number of favourable interactions or the presence of unfavourable interactions of investigated derivatives of erythromycin B with in silico constructed segment from the exit tunnel from the apicoplast of P. falciparum is the reason for their weak in vitro anti-malarial activities

HPLC ANALYSIS OF EXTRACTS OF FRESH PETALS OF PAPAVER RHOEAS L.

Papaver rhoeas L. (Papaveraceae) is an annual grass native to many regions of the world, which is known to possess several pharmacological properties. It is also known that represent a rich source of anthocyanins. In this study, the content of the anthocyanin was determined in the examined various extracts of fresh petals by HPLC analysis. The most represented anthocyanins in the extracts of Papaver rhoeas L. are delphinidin-3-O-glucoside, cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside, peonidin-3-O-glucoside, petunidin-3-O-glucoside, petunidin-3-acetylglucoside, and delphinidin-3-p-coumaroylglucoside. Acyl derivatives of anthocyanins in the water extract have not been identified. By comparing the contents of individual anthocyanins, the glycosides (polar) are better extracted with 50% alcohol solution, and their acyl derivatives are better extracted with pure alcohol. The water solution is the least suitable for anthocyanin extraction

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation