The genetic landscape of neuro-related proteins in human plasma.

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL.

Counteracting Angiotensinogen Small-Interfering RNA-Mediated Antihypertensive Effects With REVERSIR.

Background: Small-interfering RNA (siRNA) targeting hepatic AGT (angiotensinogen) mRNA depletes AGT, lowering blood pressure for up to 6 months. However, certain situations may require a rapid angiotensin increase. The REVERSIR (RVR) - reverse siRNA silencing technology a potential approach to counteract siRNA effects.

Targeting Angiotensinogen With -Acetylgalactosamine-Conjugated Small Interfering RNA to Reduce Blood Pressure.

Blood pressure management involves antihypertensive therapies blocking the renin-angiotensin system (RAS). Yet, it might be inadequate due to poor patient adherence or the so-called RAS escape phenomenon, elicited by the compensatory renin elevation upon RAS blockade. Recently, evidence points toward targeting hepatic AGT (angiotensinogen) as a novel approach to block the RAS pathway that could circumvent the RAS escape phenomenon.

Sulfur and nitrogen-containing compounds from the whole bodies of Blaps japanensis.

Pipajiains H-J (1-3), three new phenolic derivatives with an unusual sulfone group, pipajiamides A-C (4-6), three new amide derivatives, pipajiaine A (7), one new imidazole analogue, and pipajiaine B (8), a pair of new pyrrolidine derivatives, along with three known compounds were isolated from the insect Blaps japanensis. Their structures were identified by spectroscopic and computational methods. Chiral HPLC was used to separate the (-)- and (+)-antipodes of 4 and 8.

Prevention of progression of pulmonary hypertension by the Nur77 agonist 6-mercaptopurine: role of BMP signalling.

Pulmonary arterial hypertension (PAH) is a progressive fatal disease characterised by abnormal remodelling of pulmonary vessels, leading to increased vascular resistance and right ventricle failure. This abnormal vascular remodelling is associated with endothelial cell dysfunction, increased proliferation of smooth muscle cells, inflammation and impaired bone morphogenetic protein (BMP) signalling. Orphan nuclear receptor Nur77 is a key regulator of proliferation and inflammation in vascular cells, but its role in impaired BMP signalling and vascular remodelling in PAH is unknown.

Search for rare decays of and Higgs bosons to and a photon in proton-proton collisions at = 13 .

A search is presented for decays of and Higgs bosons to a meson and a photon, with the subsequent decay of the to . The analysis uses data from proton-proton collisions with an integrated luminosity of 35.9 at collected with the CMS detector at the LHC.

Increased Pancreatic Echogenicity with US: Relationship to Glycemic Progression and Incident Diabetes.

Purpose To evaluate the association between increased pancreatic echogenicity (IPE) and the risk of glycemic progression and incident diabetes. Materials and Methods This retrospective study was approved by the institutional review board, with waiver of informed consent. Consecutive individuals who had undergone abdominal ultrasonography as part of a health examination at a tertiary hospital between January 2005 and December 2011 were included.

Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

Background: The beneficial effects of parasympathetic stimulation have been reported in left heart failure, but whether it would be beneficial for pulmonary arterial hypertension (PAH) remains to be explored. Here, we investigated the relationship between parasympathetic activity and right ventricular (RV) function in patients with PAH, and the potential therapeutic effects of pyridostigmine (PYR), an oral drug stimulating the parasympathetic activity through acetylcholinesterase inhibition, in experimental pulmonary hypertension (PH).

Methods: Heart rate recovery after a maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity.

Dimeric furanocoumarins from the roots of Angelica dahurica.

Three new dimeric furanocoumarins, dahuribiethrins H-J (1-3), and a new ester coumarin, dahurinol A (4), were isolated from the roots of Angelica dahurica. Their structures were elucidated on the basis of extensive spectroscopic data including UV, IR, HRESIMS, 1D and 2D NMR. Compounds 2 and 3 exhibited inhibition of nitric oxide production in the lipopolysaccharide (LPS)-stimulated RAW 264.

Nonalcoholic Fatty Liver Disease Is Associated With QT Prolongation in the General Population.

Background: Nonalcoholic fatty liver disease (NAFLD) is independently associated with QT prolongation among patients with diabetes. It has not yet been determined whether this association remains valid in the general population. We designed an observational study to explore this association.

Ischemic electrocardiographic abnormalities and prognosis in decompensated heart failure.

Background: Identification of coronary ischemia may enable targeted diagnostic and therapeutic strategies for acute heart failure. We determined the risk of 30-day mortality associated with ischemic ECG abnormalities in patients with acute heart failure.

Methods And Results: Among 8772 patients (53.

The contribution of human OCT1, OCT3, and CYP3A4 to nitidine chloride-induced hepatocellular toxicity.

Nitidine chloride (NC), a quaternary ammonium alkaloid, has numerous pharmacological effects, such as anticancer activity. However, it was found that NC also has hepatocellular toxicity. Because organic cation transporters 1 and 3 (OCT1 and OCT3) might mediate the influx of NC into hepatocytes, multidrug and toxin extrusion 1 (MATE1) probably mediates the efflux of NC from hepatocytes, while cytochrome P450 (P450) enzymes might contribute to NC metabolism, the present study was to evaluate the contribution of OCT1, OCT3, MATE1, and P450 enzymes to NC-induced hepatocellular toxicity.

Three new triterpene saponins from Clematis chinensis.

Three new triterpene saponins, clematochinenosides H-J (1-3), were isolated from the roots and rhizomes of Clematis chinensis. Their structures were elucidated on the basis of spectroscopic means including 1D and 2D NMR experiments and hydrolysis products.