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Hypertension Research

11:52 EDT 21st August 2018 | BioPortfolio

Design, synthesis and structure-activity relationship of diaryl-ureas with novel isoxazol3,4-bpyridine-3-amino-structure as multi-target inhibitors against receptor tyrosine kinase.

Inspired by that the multi-target inhibitors against receptor tyrosine kinases (RTKs) have significantly improved the effect of clinical treatment for cancer, and based on the chemical structure of Linifanib (ABT-869, Abbott), two series of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure were designed and synthesized as multi-target inhibitors against RTKs. The preliminary biolog...

Medical Therapy for Systemic Right Ventricles: A Systematic Review (Part 1) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Patients with systemic morphological right ventricles (RVs), including congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries with a Mustard or Senning atrial baffle repair, have a high likelihood of developing systemic ventricular dysfunction. Unfortunately, there are a limited number of clinical studies on the efficacy of medical therapy for sys...

Genetic deletion of the Angiotensin-(1-7) receptor Mas leads a reduced ovulatory rate.

Angiotensin-(1-7) [Ang-(1-7)] is a component of Renin-Angiotensin System (RAS) that acts through activation of the G-protein-coupled receptor Mas. Recent studies highlight Ang-(1-7) as an intermediate of gonadotropin in ovarian physiology. Genetically Mas-deficient mice allow the investigation of Ang-(1-7) in the ovulatory process. Therefore, the present study aimed to analyze the effects of Mas g...

Nanoformulations of anticancer FGFR inhibitors with improved therapeutic index.

Fibroblast growth factor receptor (FGFR) inhibitors like ponatinib and nintedanib are clinically approved for defined cancer patient cohorts but often exert dose-limiting adverse effects. Hence, we encapsulated FGFR inhibitors ponatinib, PD173074, and nintedanib into polylactic acid nanoparticles and liposomes to enable increased tumor accumulation/specificity and reduce side effects. Different me...

Enzyme action at RNA-protein interface in DTD-like fold.

The contemporary `RNA-protein world' is exemplified by close associations between many RNAs and proteins which are necessary to carry out important biological processes. DTD-like fold, which is involved in translational proofreading, represents such RNA-protein complexes (RNPCs). Interestingly, it interacts with the substrates in the active site mostly through the main chain, and side chains are d...

Structural characterization and rheological properties of β-D-glucan from hull-less barley (Hordeum vulgare L. var. nudum Hook. f.).

A high purity of β-D-glucan (80.8%) from hull-less barley (Hordeum vulgare L. var. nudum Hook. f.) (HBBG) was isolated by alkali extraction and multi-precipitation with ethanol. The molecular weight (Mw) of HBBG was determined as 571.4 kDa with a broad distribution (Mw/Mn = 1.6) by using HPSEC. According to methylation and GC-MS analysis, HBBG was identified to be composed of (1 → 4)-...

Phytotoxicity and bioaccumulation of zinc oxide nanoparticles in rice (Oryza sativa L.).

This work focused on the toxicity evaluation of ZnO NPs and their uptake and transportation in a significant crop plant, Rice (Oryza sativa L.). Under hydroponic condition, 25, 50 and 100 mg/L ZnO NPs could inhibit the growth of rice seedlings by reducing their biomass comparing with Zn (13.82 mg/L) treatment and the control. In addition, physiological index was determined, involving the decre...

Alcohol inhibits T-cell glucose metabolism and hepatitis in ALDH2-deficient mice and humans: roles of acetaldehyde and glucocorticoids.

Aldehyde dehydrogenase 2 (ALDH2), a key enzyme to detoxify acetaldehyde in the liver, exists in both active and inactive forms in humans. Individuals with inactive ALDH2 accumulate acetaldehyde after alcohol consumption. However, how acetaldehyde affects T-cell hepatitis remains unknown.

Histological anomalies and alterations in enzyme activities of the earthworm Glyphidrillus tuberosus exposed to high concentrations of phosphogypsum.

Phosphogypsum (PG) is the major solid waste generated by phosphate fertilizer plants and is used worldwide as sulfur and calcium supplement in agricultural soil. Considering the probability of elevated doses of PG during agricultural applications, this study was carried out to assess its impact on the connective tissue, tissue cholinesterase (ChE) activity, lactate dehydrogenase (LDH) activity, an...

The IDO genetic polymorphisms and postpartum depressive symptoms: an association study in Chinese parturients who underwent cesarean section.

Postpartum depressive symptoms (PDS) are not an uncommon mood disorder in postpartum women. Our previous research indicated a role for increased tryptophan (TRP) metabolism along the kynurenine pathway (KP) in the pathogenesis of PDS. Accordingly, this study was going to investigate the association of indoleamine-2,3-dioxygenase (IDO, a key enzyme of KP) genetic polymorphisms with PDS. Seven hundr...

Association Between GSTP1 Ile105Val Genetic Polymorphism and Dependency to Heroin and Opium.

Relationship between glutathione S-transferase P1 (GSTP1, OMIM: 134660) variants and the risk of drug dependency is unknown. Chronic use of illegal drugs leads to oxidative stress, which can be alleviated by cellular detoxification mechanisms. There are several polymorphisms in the GSTP1, including Ile105Val (rs1695). This polymorphism leads to an Ile105Val amino acid change and may alter the GSTP...

Lethal Factor Domain-Mediated Delivery of Nurr1 Transcription Factor Enhances Tyrosine Hydroxylase Activity and Protects from Neurotoxin-Induced Degeneration of Dopaminergic Cells.

The orphan transcription factor nuclear receptor-related 1 protein (Nurr1, also known as NR4A2) plays a key role in embryonic development and maintenance of mesencephalic dopaminergic neurons in the substantia nigra. Nurr1 deficiency is associated with Parkinson's disease where dopaminergic neurons degenerate suggesting that counter-regulation of Nurr1 activity may have therapeutic effects. Here, ...

Microenvironmental control of glucose metabolism in tumors by regulation of pyruvate dehydrogenase.

During malignant progression cancer cells undergo a series of changes, which promote their survival, invasiveness and metastatic process. One of them is a change in glucose metabolism. Unlike normal cells, which mostly rely on the tricarboxylic acid cycle (TCA), many cancer types rely on glycolysis. Pyruvate dehydrogenase complex (PDC) is the gatekeeper enzyme between these two pathways and is res...

Cyanophycin synthesis optimizes nitrogen utilization in the unicellular cyanobacterium sp. PCC 6803.

Cyanophycin is a carbon/nitrogen storage polymer widely distributed in most cyanobacterial strains and in a few heterotrophic bacteria. It is a non-ribosomal polypeptide consisting of equimolar amounts of aspartate and arginine. Here, we focused on the physiological function and cell biology of cyanophycin in the unicellular non-diazotrophic cyanobacterium sp. PCC 6803. To study the cellular loca...

Variability in the ocular phenotype in mucopolysaccharidosis.

Mucopolysaccharidoses (MPSs) are a heterogeneous group of lysosomal storage disorders. Ocular complications (such as corneal clouding, retinopathy and optic neuropathy) are common. Notably, there is a paucity of data on the effect of genotype and systemic treatments (enzyme replacement therapy or haematopoietic stem cell transplantation) on the ocular phenotype in MPS. We prospectively studied th...

An elusive adenylate cyclase complicit in cholera is exposed.

The intestinal consequences of cholera enterotoxin are caused by activation of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel through the actions of an as-yet-unknown adenylate cyclase. A new study hunts down this elusive enzyme, showing that mouse and human intestinal epithelium functionally and structurally pair adenylate cyclase isoform 6 (AC6) with CFTR. These fin...

Coupled Transmembrane Substrate Docking and Helical Unwinding in Intramembrane Proteolysis of Amyloid Precursor Protein.

Intramembrane-cleaving proteases (I-CLiPs) play crucial roles in physiological and pathological processes, such as Alzheimer's disease and cancer. However, the mechanisms of substrate recognition by I-CLiPs remain poorly understood. The aspartic I-CLiP presenilin is the catalytic subunit of the γ-secretase complex, which releases the amyloid-β peptides (Aβs) through intramembrane proteolysis of...

Extracellular vesicles protect glucuronidase model enzymes during freeze-drying.

Extracellular vesicles (EVs) are natural nanoparticles that play important roles in intercellular communication and are increasingly studied for biosignalling, pathogenesis and therapy. Nevertheless, little is known about optimal conditions for their transfer and storage, and the potential impact on preserving EV-loaded cargoes. We present the first comprehensive stability assessment of different...

Cardiovascular Interactions between Fibroblast Growth Factor-23 and Angiotensin II.

Both the activation of the renin angiotensin aldosterone system (RAAS) and elevations of circulating Fibroblast Growth Factor-23 (FGF-23) have been implicated in the pathogenesis of left ventricular hypertrophy (LVH) in chronic kidney disease. To investigate potential cross-talk between RAAS and FGF-23, we administered angiotensin II (Ang II) to wild-type rodents and the Hyp mouse model of excess ...

Intracerebroventricular administration of bone marrow-derived cells attenuates angiotensin II-initiated neurogenic hypertension in rats.

Bone marrow-derived cells exert anti-inflammatory actions and can migrate into the brain. However, their role in the development of neurogenic hypertension remains unclear. A hyperactive renin-angiotensin system and inflammation in the brain are mechanisms that contribute to angiotensin II-initiated neurogenic hypertension. We hypothesized that bone marrow-derived cells in the brain attenuate the ...

Hypertension-induced cognitive impairment: insights from prolonged angiotensin II infusion in mice.

The causal relation between hypertension and cerebral small vessel disease (cSVD) remains elusive, and appropriate animal models are scarce. We aimed to assess the relevance of prolonged angiotensin II-induced hypertension in mice for the study of cSVD.Adult male C57BL/6 mice were continuously infused for 3 months with Angiotensin II (Ang II; 2 µg/kg/min, sc) or saline (control) via osmotic min...

In a pilot study, reduced fatty acid desaturase 1 function was associated with nonalcoholic fatty liver disease and response to treatment in children.

FADS1 gene encodes delta 5 desaturase, a rate-limiting enzyme in the metabolism of n-3 and n-6 polyunsaturated fatty acids (PUFAs). Minor alleles of FADS1 locus polymorphisms are associated with reduced FADS1 expression and intra-hepatic fat accumulation. However, the relationship between FADS1 expression and pediatric nonalcoholic fatty liver disease (NAFLD) risk remains to be explored.

Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice.

Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinctio...

Levansucrase from Halomonas smyrnensis AAD6: first halophilic GH-J clan enzyme recombinantly expressed, purified, and characterized.

Fructans, homopolymers of fructose produced by fructosyltransferases (FTs), are emerging as intriguing components in halophiles since they are thought to be associated with osmotic stress tolerance and overall fitness of microorganisms and plants under high-salinity conditions. Here, we report on the full characterization of the first halophilic FT, a levansucrase from Halomonas smyrnensis AAD6 (H...

Predictive classification models and targets identification for betulin derivatives as Leishmania donovani inhibitors.

Betulin derivatives have been proven effective in vitro against Leishmania donovani amastigotes, which cause visceral leishmaniasis. Identifying the molecular targets and molecular mechanisms underlying their action is a currently an unmet challenge. In the present study, we tackle this problem using computational methods to establish properties essential for activity as well as to screen betulin ...

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