C-type natriuretic peptide/cGMP/FoxO3 signaling attenuates hyperproliferation of pericytes from patients with pulmonary arterial hypertension.

Pericyte dysfunction, with excessive migration, hyperproliferation, and differentiation into smooth muscle-like cells contributes to vascular remodeling in Pulmonary Arterial Hypertension (PAH). Augmented expression and action of growth factors trigger these pathological changes. Endogenous factors opposing such alterations are barely known.

Isolation and characterization of a newly discovered plant growth-promoting endophytic fungal strain from the genus Talaromyces.

In the Kandi zone of Punjab, India, root and rhizospheric soil samples were collected from the local vegetation near the Shivalik mountain foothills. Fifteen fungal colonies exhibiting distinct cultural morphology on Potato Dextrose Agar (PDA) plates were selected for plant-microbe interaction studies. Among these, the isolate HNB9 was identified as a nonpathogenic root colonizer.

Network pharmacology and molecular docking analysis on potential molecular targets and mechanism of action of BRAF inhibitors for application in wound healing.

Topical application of BRAF inhibitors has been shown to accelerate wound healing in murine models, which can be extrapolated into clinical applications. The aim of the study was to identify suitable pharmacological targets of BRAF inhibitors and elucidate their mechanisms of action for therapeutic applicability in wound healing, by employing bioinformatics tools including network pharmacology and molecular docking. The potential targets for BRAF inhibitors were obtained from SwissTargetPrediction, DrugBank, CTD, Therapeutic Target Database, and Binding Database.

Interaction studies of and sp. ISTPL4 and their synergistic role in growth promotion in rice.

Rapid urbanization and globalization demand increasing agricultural productivity. Soil nutrient supply capacity is continuously decreasing due to soil erosion, degradation, salt deposition, undesired element, metal deposition, water scarcity, and an uneven nutrient delivery system. Rice cultivation requires a large amount of water which is becoming detrimental due to these activities.

Deciphering the Precise Target for Saroglitazar Associated Antiangiogenic Effect: A Computational Synergistic Approach.

Antidiabetic drugs that have a secondary pharmacological effect on angiogenesis inhibition may help diabetic patients delay or avoid comorbidities caused by angiogenesis including malignancies. In recent studies, saroglitazar has exhibited antiangiogenic effects in diabetic retinopathy. The current study investigates the antiangiogenic effects of saroglitazar utilizing the chicken chorioallantoic membrane (CAM) assay and then identifies its precise mode of action on system-level protein networks.

Targeting Wnt-ß-Catenin-FOSL Signaling Ameliorates Right Ventricular Remodeling.

Background: The ability of the right ventricle (RV) to adapt to an increased pressure afterload determines survival in patients with pulmonary arterial hypertension. At present, there are no specific treatments available to prevent RV failure, except for heart/lung transplantation. The wingless/int-1 (Wnt) signaling pathway plays an important role in the development of the RV and may also be implicated in adult cardiac remodeling.

Protocol for competition and sequencing of mycobacterium isolated from infected guinea pigs.

We describe steps for gDNA isolation from mycobacterium strains isolated from guinea pig lungs. We detail steps for infection of guinea pigs with , followed by growth, gDNA isolation, and whole genome sequencing. We also describe an competition experiment to determine the selective advantage of one strain over another.

Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life.

Obesity is a pre-disposing condition for chronic obstructive pulmonary disease, asthma, and pulmonary arterial hypertension. Accumulating evidence suggests that metabolic influences during development can determine chronic lung diseases (CLD). We demonstrate that maternal obesity causes early metabolic disorder in the offspring.

Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival.

Rationale: The MSTs (mammalian Ste20-like kinases) 1/2 are members of the HIPPO pathway that act as growth suppressors in adult proliferative diseases. Pulmonary arterial hypertension (PAH) manifests by increased proliferation and survival of pulmonary vascular cells in small PAs, pulmonary vascular remodeling, and the rise of pulmonary arterial pressure. The role of MST1/2 in PAH is currently unknown.

Compromised base excision repair pathway in Mycobacterium tuberculosis imparts superior adaptability in the host.

Tuberculosis caused by Mycobacterium tuberculosis (Mtb) is a significant public health concern, exacerbated by the emergence of drug-resistant TB. To combat the host's dynamic environment, Mtb encodes multiple DNA repair enzymes that play a critical role in maintaining genomic integrity. Mtb possesses a GC-rich genome, rendering it highly susceptible to cytosine deaminations, resulting in the occurrence of uracils in the DNA.

A survey of fasting practices and acceptance of an intervention for achieving control in diabetes during Ramadan.

Background: Many people with diabetes, who practise Islam, are passionate about fasting during Ramadan despite their medical condition and exemption from the religion. These patients are at risk of hypoglycaemia, hyperglycaemia, diabetic ketoacidosis, dehydration and thrombosis. We evaluated the acceptability of an individualized management plan for such people.

C-type natriuretic peptide moderates titin-based cardiomyocyte stiffness.

Heart failure is often accompanied by titin-dependent myocardial stiffness. Phosphorylation of titin by cGMP-dependent protein kinase I (PKGI) increases cardiomyocyte distensibility. The upstream pathways stimulating PKGI-mediated titin phosphorylation are unclear.

Isoform-specific characterization of class I histone deacetylases and their therapeutic modulation in pulmonary hypertension.

Pharmacological modulation of class I histone deacetylases (HDAC) has been evaluated as a therapeutic strategy for pulmonary hypertension (PH) in experimental models of PH. However, information of their expression, regulation and transcriptional targets in human PH and the therapeutic potential of isoform-selective enzyme modulation are lacking. Comprehensive analysis of expression and regulation of class I HDACs (HDAC1, HDAC2, HDAC3 and HDAC8) was performed in cardiopulmonary tissues and adventitial fibroblasts isolated from pulmonary arteries (PAAF) of idiopathic pulmonary arterial hypertension (IPAH) patients and healthy donors.

Biopriming with Piriformospora indica ameliorates cadmium stress in rice by lowering oxidative stress and cell death in root cells.

Piriformospora indica is known for plant growth promotion and abiotic stress alleviation potential in several agricultural crops. However, a systemic analysis is warranted to explore potential application of this important fungus to augment heavy metal tolerance in rice. The present study explores potential of P.

A RASSF1A-HIF1α loop drives Warburg effect in cancer and pulmonary hypertension.

Hypoxia signaling plays a major role in non-malignant and malignant hyperproliferative diseases. Pulmonary hypertension (PH), a hypoxia-driven vascular disease, is characterized by a glycolytic switch similar to the Warburg effect in cancer. Ras association domain family 1A (RASSF1A) is a scaffold protein that acts as a tumour suppressor.

Silver-Catalyzed Carboxylative Cyclization of Primary Propargyl Alcohols with CO.

By using silver complexes with bulky ligands such as DavePhos or N-heterocyclic carbenes, propargylic alcohols are smoothly converted with CO into a unique class of unexplored cyclic alkylidene carbonates. These systems, for the first time, also achieve the direct carboxylative cyclization of primary propargylic alcohols. The silver-DavePhos catalyst is further applied for the bis-carboxylative cyclization of primary propargyl derivatives, thereby providing an effective route to a series of previously inaccessible and industrially relevant α-alkylidene cyclic carbonates.

3'-Deoxy-3'-[18F]Fluorothymidine Positron Emission Tomography Depicts Heterogeneous Proliferation Pathology in Idiopathic Pulmonary Arterial Hypertension Patient Lung.

Background: Pulmonary vascular cell hyperproliferation is characteristic of pulmonary vascular remodeling in pulmonary arterial hypertension. A noninvasive imaging biomarker is needed to track the pathology and assess the response to novel treatments targeted at resolving the structural changes. Here, we evaluated the application of radioligand 3'-deoxy-3'-[18F]-fluorothymidine (FLT) using positron emission tomography.

FoxO3 an important player in fibrogenesis and therapeutic target for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal parenchymal lung disease with limited therapeutic options, with fibroblast-to-myofibroblast transdifferentiation and hyperproliferation playing a major role. Investigating -cultured (myo)fibroblasts from human IPF lungs as well as fibroblasts isolated from bleomycin-challenged mice, Forkhead box O3 (FoxO3) transcription factor was found to be less expressed, hyperphosphorylated, and nuclear-excluded relative to non-diseased controls. Downregulation and/or hyperphosphorylation of FoxO3 was reproduced by exposure of normal human lung fibroblasts to various pro-fibrotic growth factors and cytokines (FCS, PDGF, IGF1, TGF-β1).

Human Cyclophilin B forms part of a multi-protein complex during erythrocyte invasion by Plasmodium falciparum.

Invasion of human erythrocytes by Plasmodium falciparum merozoites involves multiple interactions between host receptors and their merozoite ligands. Here we report human Cyclophilin B as a receptor for PfRhopH3 during merozoite invasion. Localization and binding studies show that Cyclophilin B is present on the erythrocytes and binds strongly to merozoites.

Selective enzymatic esterification of lignin model compounds in the ball mill.

A lipase-catalyzed esterification of lignin model compounds in the ball mill was developed combining the advantages of enzyme catalysis and mechanochemistry. Under the described conditions, the primary aliphatic hydroxy groups present in the substrates were selectively modified by the biocatalyst to afford monoesterified products. Amongst the tested lipases, CALB proved to be the most effective biocatalyst for these transformations.

Organic Dye-Catalyzed Atom Transfer Radical Addition-Elimination (ATRE) Reaction for the Synthesis of Perfluoroalkylated Alkenes.

An atom transfer radical addition elimination (ATRE) reaction of terminal alkenes with perfluoroalkyl halides under visible light is described. The photoredox catalysis with Eosin Y provides perfluoroalkenes in good yields. The reaction has been utilized for the late stage perfluoroalkenylation of an estrone-derived alkene.

Organocatalytic Chemoselective Primary Alcohol Oxidation and Subsequent Cleavage of Lignin Model Compounds and Lignin.

A one-pot two-step degradation of lignin β-O-4 model compounds initiated by preferred oxidation of the primary over the secondary hydroxyl groups with a TEMPO/DAIB system has been developed [TEMPO=2,2,6,6-tetramethylpiperidine-N-oxyl, DAIB=(diacetoxy)iodobenzene]. The oxidised products are then cleaved by proline-catalysed retro-aldol reactions. This degradation methodology produces simple aromatics in good yields from lignin model compounds at room temperature with an extension to organosolv beech-wood lignin (L1) resulting in known cleavage products.

Role of exchange protein directly activated by cAMP (EPAC1) in breast cancer cell migration and apoptosis.

Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death.

A novel Pfs38 protein complex on the surface of Plasmodium falciparum blood-stage merozoites.

Background: The Plasmodium genome encodes for a number of 6-Cys proteins that contain a module of six cysteine residues forming three intramolecular disulphide bonds. These proteins have been well characterized at transmission as well as hepatic stages of the parasite life cycle. In the present study, a large complex of 6-Cys proteins: Pfs41, Pfs38 and Pfs12 and three other merozoite surface proteins: Glutamate-rich protein (GLURP), SERA5 and MSP-1 were identified on the Plasmodium falciparum merozoite surface.