MicroRNA-140-5p and SMURF1 regulate pulmonary arterial hypertension.

Loss of the growth-suppressive effects of bone morphogenetic protein (BMP) signaling has been demonstrated to promote pulmonary arterial endothelial cell dysfunction and induce pulmonary arterial smooth muscle cell (PASMC) proliferation, leading to the development of pulmonary arterial hypertension (PAH). MicroRNAs (miRs) mediate higher order regulation of cellular function through coordinated modulation of mRNA targets; however, miR expression is altered by disease development and drug therapy. Here, we examined treatment-naive patients and experimental models of PAH and identified a reduction in the levels of miR-140-5p.

Ethnobotany, chemical constituents and biological activities of the flowers of Hydnora abyssinica A.Br. (Hydnoraceae).

Hydnora abyssinica A.Br. (Hydnoraceae), a holoparasitic herb, is for the first time recorded for Abyan governorate of South Yemen.

Herpes zoster and the search for an effective vaccine.

Primary infection with varicella zoster virus (VZV), an exclusively human neurotrophic alphaherpsesvirus, results in varicella, known more commonly as chickenpox. Like other alphaherpesviruses, VZV establishes latency in the sensory ganglia and can reactivate to cause herpes zoster (also known as shingles), a painful and debilitating disease, especially in elderly and immunocompromised individuals. The overall incidence of herpes zoster in Europe and the United States is three per 1000 people, but increases sharply after 60 years of age to 10 per 1000 people.

Minimal spaser threshold within electrodynamic framework: Shape, size and modes.

It is known (yet often ignored) from quantum mechanical or energetic considerations, that the threshold gain of the quasi-static spaser depends only on the dielectric functions of the metal and the gain material. Here, we derive this result from the purely classical electromagnetic scattering framework. This is of great importance, because electrodynamic modelling is far simpler than quantum mechanical one.

Head-to-head comparison of the impact of Aurora A, Aurora B, Repp86, CDK1, CDK2 and Ki67 expression in two of the most relevant gynaecological tumor entities.

Purpose: The dysregulation of cell cycle kinases plays a crucial role in carcinogenesis and the expression of various kinases has been attributed to aggressive tumor growth and an unfavourable prognosis in oncological patients. We, therefore, aimed to evaluate the expression of Ki67 among five additional cell cycle kinases in a collective of mammary and ovarian tumor specimens and to find a correlation with clinicopathological parameters.

Methods: 76 mammary and 93 ovarian benign and malignant tumor samples were immunohistochemically stained and evaluated for the expression of Aurora A and B, Repp86, CDK1 and 2 (only breast specimens) and Ki67.

Heart rate reduction with ivabradine promotes shear stress-dependent anti-inflammatory mechanisms in arteries.

Blood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. Low WSS promotes vascular inflammation and atherosclerosis whereas high uniform WSS is protective. Ivabradine decreases heart rate leading to altered haemodynamics.

New outcomes of Lewis base addition to diboranes(4): electronic effects override strong steric disincentives.

Two surprising new outcomes of the reaction of Lewis bases with dihalodiboranes(4) are presented, including sp(2)-sp(3) diboranes in which the Lewis base unit is bound to a highly sterically congested boron atom, and a rearranged double base adduct. The results provide a fuller understanding of the reactivity of diboranes, a poorly-understood class of molecule of critical importance to synthetic organic chemistry.

Chilenopeptins A and B, Peptaibols from the Chilean Sepedonium aff. chalcipori KSH 883.

The Chilean Sepedonium aff. chalcipori strain KSH 883, isolated from the endemic Boletus loyo Philippi, was studied in a polythetic approach based on chemical, molecular, and biological data. A taxonomic study of the strain using molecular data of the ITS, EF1-α, and RPB2 barcoding genes confirmed the position of the isolated strain within the S.

Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer.

Purpose: To characterise the prevalence of pathogenic germline mutations in BRCA1 and BRCA2 in families with breast cancer (BC) and ovarian cancer (OC) history.

Patients And Methods: Data from 21 401 families were gathered between 1996 and 2014 in a clinical setting in the German Consortium for Hereditary Breast and Ovarian Cancer, comprising full pedigrees with cancer status of all individual members at the time of first counselling, and BRCA1/2 mutation status of the index patient.

Results: The overall BRCA1/2 mutation prevalence was 24.

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.

Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).

Alteration of STR profiles in ovarian carcinoma cells during primary culture.

Purpose: Cell authentication is a necessary procedure to avoid scientific data from cell culture experiments with cross-contamination or false classification. A genetic fingerprint pattern of a specimen by short tandem repeats (STR) is self-evident. Due to high amount of chromosomal rearrangements, known in epithelia ovary cancer cells and the instable STR pattern described in other tumour entities like leukaemia, this study explores the suitability of STR profiling for primary cultured epithelial ovary cancer cells.

Structure and Absolute Configuration of Pseudohygrophorones A(12) and B(12), Alkyl Cyclohexenone Derivatives from Hygrophorus abieticola (Basidiomycetes).

Pseudohygrophorones A(12) (1) and B(12) (2), the first naturally occurring alkyl cyclohexenones from a fungal source, and the recently reported hygrophorone B(12) (3) have been isolated from fruiting bodies of the basidiomycete Hygrophorus abieticola Krieglst. ex Gröger & Bresinsky. Their structures were assigned on the basis of extensive one- and two-dimensional NMR spectroscopic analysis as well as ESI-HRMS measurements.

Unprecedented Borane, Diborane(3), Diborene, and Borylene Ligands via Pt-Mediated Borane Dehydrogenation.

Reactions of an aryldihydroborane with a Pt(0) complex lead to a range of novel products, including complexes with bridging diborene and diborane(3) ligands and a complex with both borylene and borane (M → B) ligands. The products imply varying degrees of dehydrogenation of the boron centers with concomitant formation of boron-boron bonds, which in one case is later broken. These reactions show that although the dehydrocoupling of dihydroboranes is not a straightforward process in this case, the reactions are capable of connecting boron atoms in unusual ways, leading to unprecedented bonding motifs.

Bromoenol Lactone Attenuates Nicotine-Induced Breast Cancer Cell Proliferation and Migration.

Objectives: Calcium independent group VIA phospholipase A2 (iPLA2β) and Matrix Metalloproteinase-9 (MMP-9) are upregulated in many disease states; their involvement with cancer cell migration has been a recent subject for study. Further, the molecular mechanisms mediating nicotine-induced breast cancer cell progression have not been fully investigated. This study aims to investigate whether iPLA2β mediates nicotine-induced breast cancer cell proliferation and migration through both in-vitro and in-vivo techniques.

Pulmonary artery denervation reduces pulmonary artery pressure and induces histological changes in an acute porcine model of pulmonary hypertension.

Background: Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level.

Heme oxygenase-1 suppresses a pro-inflammatory phenotype in monocytes and determines endothelial function and arterial hypertension in mice and humans.

Aims: Heme oxygenase-1 (HO-1) confers protection to the vasculature and suppresses inflammatory properties of monocytes and macrophages. It is unclear how HO-1 determines the extent of vascular dysfunction in mice and humans.

Methods And Results: Decreased HO-1 activity and expression was paralleled by increased aortic expression and activity of the nicotinamide dinucleotide phosphate oxidase Nox2 in HO-1 deficient Hmox1⁻/⁻ and Hmox1(⁺/⁻) compared with Hmox1⁺/⁺ mice.

A study on the biosynthesis of hygrophorone B(12) in the mushroom Hygrophorus abieticola reveals an unexpected labelling pattern in the cyclopentenone moiety.

The hitherto unknown natural formation of hygrophorones, antibacterial and antifungal cyclopentenone derivatives from mushrooms, was investigated for hygrophorone B(12) in Hygrophorus abieticola Krieglst. ex Gröger & Bresinsky by feeding experiments in the field using (13)C labelled samples of D-glucose and sodium acetate. The incorporation of (13)C isotopes was extensively studied using 1D and 2D NMR spectroscopy as well as ESI-HRMS analyses.

Discovery and Optimization of 4-(8-(3-Fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic Acid, an Improved PDE4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease (COPD).

Herein we describe the optimization of a series of PDE4 inhibitors, with special focus on solubility and pharamcokinetics, to clinical compound 2, 4-(8-(3-fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic acid. Although compound 2 produces emesis in humans when given as a single dose, its exemplary pharmacokinetic properties enabled a novel dosing regime comprising multiple escalating doses and the resultant achievement of high plasma drug levels without associated nausea or emesis.

Methylated derivatives of myricetin enhance life span in Caenorhabditis elegans dependent on the transcription factor DAF-16.

Only certain flavonoids have been shown to enhance life span. This was pointed out for e.g.

Comparative Chemical Composition and Antioxidant Properties of the Essential Oils of three Sideritis libanotica Subspecies.

The phytochemical composition of the essential oils of three Sideritis libanotica subspecies, namely S. libanotica ssp. libanotica, S.

Composition, antibacterial, antioxidant and antiproliferative activities of essential oils from three Origanum species growing wild in Lebanon and Greece.

The essential oils from Origanum dictamnus, Origanum libanoticum and Origanum microphyllum were analysed by GC-MS, finding carvacrol, p-cymene, linalool, γ-terpinene and terpinen-4-ol as major components. The antioxidant activity by the DPPH and FRAP tests and the antiproliferative activity against two human cancer cell lines, LoVo and HepG2, were investigated, showing that the essential oil of O. dictamnus was statistically the most inhibitory on both the cell lines, while all the oils exerted a weak antioxidant activity.

Ethnopharmacological survey of medicinal plants used in traditional medicine by the communities of Mount Hermon, Lebanon.

Ethnopharmacological Relevance: Medicinal plant species in Lebanon are experiencing severe threats because of various environmental conditions, human expansion footprints and recent growing global demand. Organized research and information on indigenous medicinal plants and knowledge have been very limited and little efforts have been invested to develop a complete inventory for native medicinal plants and associated traditional knowledge in the country. Recognized as a key biodiversity area of the Mediterranean Basin, Mount Hermon hosts important richness of medicinal plants that has been traditionally used in treatment of many illnesses since generations.

A fluorescence-based bioassay for antibacterials and its application in screening natural product extracts.

The reliable assessment of the biological activity of a minor component embedded in a complex matrix of several hundred compounds is a difficult but common task in the search for natural product-based antibiotics, for example, by bioassay-guided fractionation. To quantify the antibiotic properties, it is necessary to assess the cell viability. Direct measurements use CFU counts, OD measurements or detection via fluorescent or reducible dyes.