The laboratory rat emerges as a useful tool for studying the interaction between the host and its microbiome. To advance principles relevant to the human microbiome, we systematically investigated and defined the multitissue microbial biogeography of healthy Fischer 344 rats across their lifespan. Microbial community profiling data were extracted and integrated with host transcriptomic data from the Sequencing Quality Control consortium.
View Article and Find Full Text PDFCircular RNAs (circRNAs) belong to a unique class of endogenously expressed non-protein-coding RNAs with a distinct circularized structure, characterized by the absence of 5'-cap and 3'-polyadenylate ends. They are generally formed through back-splicing from pre-mRNAs. They serve as regulators of transcription and splicing, and act as sponges for microRNAs (miRNAs) and RNA-binding proteins, thereby modulating the expression of target genes.
View Article and Find Full Text PDFThe laboratory rat emerges as a useful tool for studying the interaction between the host and its microbiome. To advance principles relevant to the human microbiome, we systematically investigated and defined a multi-tissue full lifespan microbial biogeography for healthy Fischer 344 rats. Microbial community profiling data was extracted and integrated with host transcriptomic data from the Sequencing Quality Control (SEQC) consortium.
View Article and Find Full Text PDFLong non-coding RNAs (lncRNAs) are endogenously expressed RNAs longer than 200 nt that are not translated into proteins. In general, lncRNAs bind to mRNA, miRNA, DNA, and proteins and regulate gene expression at various cellular and molecular levels, including epigenetics, transcription, post-transcription, translation, and post-translation. LncRNAs play important roles in many biological processes, such as cell proliferation, apoptosis, cell metabolism, angiogenesis, migration, endothelial dysfunction, endothelial-mesenchymal transition, regulation of cell cycle, and cellular differentiation, and have become an important topic of study in genetic research in health and disease due to their close link with the development of various diseases.
View Article and Find Full Text PDFSmall nucleolar RNAs (snoRNAs) are non-coding RNA molecules that range from 60 to 300 nucleotides in length and are primarily located in the nucleoli of cells. They play a critical role in modifying ribosomal RNA and can also regulate alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression can affect numerous cellular processes, including cell proliferation, apoptosis, angiogenesis, fibrosis, and inflammation, making them a promising target for diagnostics and treatment of various human pathologies.
View Article and Find Full Text PDFELK3 is upregulated in blood and pulmonary vascular cells of PAH patients and may play a significant role in PAH potentially through modulating BMPR2 signaling.
View Article and Find Full Text PDFBone morphogenic protein receptor 2 (BMPR2) expression and signaling are impaired in pulmonary arterial hypertension (PAH). How BMPR2 signaling is decreased in PAH is poorly understood. Protein tyrosine phosphatases (PTPs) play important roles in vascular remodeling in PAH.
View Article and Find Full Text PDFNutraceuticals have emerged as potential compounds to attenuate the COVID-19 complications. Precisely, these food additives strengthen the overall COVID treatment and enhance the immunity of a person. Such compounds have been used at a large scale, in almost every household due to their better affordability and easy access.
View Article and Find Full Text PDFCircular RNAs (circRNAs) are endogenous, covalently circularised, non-protein-coding RNAs generated from back-splicing. Most circRNAs are very stable, highly conserved, and expressed in a tissue-, cell- and developmental stage-specific manner. circRNAs play a significant role in various biological processes, such as regulation of gene expression and protein translation sponging of microRNAs and binding with RNA-binding proteins.
View Article and Find Full Text PDFExtrachromosomal DNA (ecDNA) is often found in cancerous cells, and numerous scientific investigations have already shown that ecDNA-mediated oncogene amplification which contributes to cancer therapy resistance. This ecDNA is found to be essential for enhancing gene transcription and resistance to chemotherapeutic drugs, as well as promoting tumor heterogeneity and reversing tumor phenotypes, suggesting that it plays a key role in carcinogenesis. The ecDNA induces tumors to become hostile which results in a lower survival rate and chemotherapy tolerance.
View Article and Find Full Text PDFBackground: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COPD overlap (ACO). Patients characterized with ACO have increased disease severity; however, the mechanisms driving this have not been widely studied.
Objectives: This study sought to characterize the phenotypic and transcriptomic features of experimental ACO in mice induced by chronic house dust mite antigen and cigarette smoke exposure.
Lung diseases, such as asthma, chronic obstructive pulmonary diseases (COPD), and cystic fibrosis (CF), are among the leading causes of mortality and morbidity globally. They contribute to substantial economic burdens on society and individuals. Currently, only a few treatments are available to slow the development and progression of these diseases.
View Article and Find Full Text PDFIncreased inflammasome responses are strongly implicated in inflammatory diseases; however, their specific roles are incompletely understood. Therefore, we sought to examine the roles of nucleotide-binding oligomerization domain-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) and absent in melanoma-2 (AIM2) inflammasomes in cigarette smoke-induced inflammation in a model of experimental chronic obstructive pulmonary disease (COPD). We targeted NLRP3 with the inhibitor MCC950 given prophylactically or therapeutically and examined Aim2 mice in cigarette smoke-induced experimental COPD.
View Article and Find Full Text PDFMaternal iron deficiency occurs in 40-50% of all pregnancies and is associated with an increased risk of respiratory disease and asthma in children. We used murine models to examine the effects of lower iron status during pregnancy on lung function, inflammation and structure, as well as its contribution to increased severity of asthma in the offspring. A low iron diet during pregnancy impairs lung function, increases airway inflammation, and alters lung structure in the absence and presence of experimental asthma.
View Article and Find Full Text PDFBackground: Obesity is a risk factor for asthma, and obese asthmatic individuals are more likely to have severe, steroid-insensitive disease. How obesity affects the pathogenesis and severity of asthma is poorly understood. Roles for increased inflammasome-mediated neutrophilic responses, type 2 immunity, and eosinophilic inflammation have been described.
View Article and Find Full Text PDFArteriovenous malformations are a vascular anomaly typically present at birth, characterized by an abnormal connection between an artery and a vein (bypassing the capillaries). These high flow lesions can vary in size and location. Therapeutic approaches are limited, and AVMs can cause significant morbidity and mortality.
View Article and Find Full Text PDFPulmonary arterial hypertension (PAH) is a debilitating condition of the pulmonary circulatory system that occurs in patients of all ages and if untreated, eventually leads to right heart failure and death. Despite existing medical treatment options that improve survival and quality of life, the disease remains incurable. Thus, there is an urgent need to develop novel therapies to treat this disease.
View Article and Find Full Text PDFCurr Opin Pharmacol
August 2021
Pulmonary arterial hypertension (PAH) is a debilitating multifactorial disease characterized by progressive pulmonary vascular remodeling, elevated pulmonary arterial pressure, and pulmonary vascular resistance, resulting in right ventricular failure and subsequent death. Current available therapies do not reverse the disease, resulting in a persistent high morbidity and mortality. Thus, there is an urgent unmet medical need for novel effective therapies to better treat patients with PAH.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
September 2021
Right ventricular (RV) function is the predominant determinant of survival in patients with pulmonary arterial hypertension (PAH). In preclinical models, pharmacological activation of BMP (bone morphogenetic protein) signaling with FK506 (tacrolimus) improved RV function by decreasing RV afterload. FK506 therapy further stabilized three patients with end-stage PAH.
View Article and Find Full Text PDFPulmonary Arterial Hypertension (PAH) is a disease of the pulmonary arteries, that is characterized by progressive narrowing of the pulmonary arterial lumen and increased pulmonary vascular resistance, ultimately leading to right ventricular dysfunction, heart failure and premature death. Current treatments mainly target pulmonary vasodilation and leave the progressive vascular remodeling unchecked resulting in persistent high morbidity and mortality in PAH even with treatment. Therefore, novel therapeutic strategies are urgently needed.
View Article and Find Full Text PDFNo prior proteomic screening study has centred on the right ventricle (RV) in pulmonary arterial hypertension (PAH). This study investigates the circulating proteomic profile associated with right heart maladaptive phenotype (RHMP) in PAH.Plasma proteomic profiling was performed using multiplex immunoassay in 121 (discovery cohort) and 76 (validation cohort) PAH patients.
View Article and Find Full Text PDFEstrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study, we demonstrate that at physiological concentrations, sex steroids, including testosterone and estriol, induce membrane stress responses in This is characterized by increased virulence and consequent inflammation and release of proinflammatory outer membrane vesicles promoting persistence of the bacteria.
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