OTUD3 prevents ulcerative colitis by inhibiting microbiota-mediated STING activation.

Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are believed to play crucial roles in the pathogenesis of UC, but the influence of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remains poorly understood. Here, we demonstrate that OTU deubiquitinase 3 (OTUD3) suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3'3'-cGAMP) in the colon by deubiquitinating stimulator of interferon genes (STING).

Intestinal Foxl1+ cell-derived CXCL12 maintains epithelial homeostasis by modulating cellular metabolism.

Several mesenchymal cell populations are known to regulate intestinal stem cell (ISC) self-renewal and differentiation. However, the influences of signaling mediators derived from mesenchymal cells other than ISC niche factors on epithelial homeostasis remain poorly understood. Here, we show that host and microbial metabolites, such as taurine and gamma-aminobutyric acid (GABA), act on PDGFRαhigh Foxl1high sub-epithelial mesenchymal cells to regulate their transcription.

Epithelial miR-215 negatively modulates Th17-dominant inflammation by inhibiting CXCL12 production in the small intestine.

MicroRNAs are a class of non-coding short-chained RNAs that control cellular functions by downregulating their target genes. Recent research indicates that microRNAs play a role in the maintenance of gut homeostasis. miR-215 was found to be highly expressed in epithelial cells of the small intestine; however, the involvement of miR-215 in gut immunity remains unknown.

TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes.

B cells produce high amounts of cytokines and immunoglobulins in response to lipopolysaccharide (LPS) stimulation. Calcium signaling cascades are critically involved in cytokine production of T cells, and the cytosolic calcium concentration is regulated by calcium-activated monovalent cation channels (CAMs). Calcium signaling is also implicated in B cell activation; however, its involvement in the cytokine production of LPS-stimulated B cells remains less well characterized.

Relationship of Central Venous Pressure to Body Fluid Volume Status and Its Prognostic Implication in Patients With Acute Decompensated Heart Failure.

Background: Although central venous pressure (CVP) is a surrogate measure of preload in patients with acute decompensated heart failure (ADHF), it is a multifactorial index influenced not only by fluid volume status, but also by cardiac pump function and other factors. We aimed to elucidate the individual pathophysiological factors of CVP elevation in patients with ADHF by assessing the relationship between CVP and extracellular fluid volume status (EVS).

Methods And Results: We quantified EVS in 100 patients with ADHF with the use of bioelectrical impedance analysis.

Non-Ischemic Heart Failure With Reduced Ejection Fraction Is Associated With Altered Intestinal Microbiota.

Background: Research suggests that heart failure with reduced ejection fraction (HFrEF) is a state of systemic inflammation that may be triggered by microbial products passing into the bloodstream through a compromised intestinal barrier. However, whether the intestinal microbiota exhibits dysbiosis in HFrEF patients is largely unknown.

Methods and results: Twenty eight non-ischemic HFrEF patients and 19 healthy controls were assessed by 16S rRNA analysis of bacterial DNA extracted from stool samples.

A novel scoring system to predict delirium and its relationship with the clinical course in patients with acute decompensated heart failure.

Background: Delirium is known to be a poor prognostic factor in patients with acute decompensated heart failure (ADHF). The purpose of this study was to determine predictors of delirium on admission of ADHF patients, and to establish a scoring formula to identify patients at high risk for delirium.

Methods And Results: We recorded the Intensive Care Delirium Screening Checklist (ICDSC) score in 120 ADHF patients during their stay in the coronary care unit (CCU).

Transtubular Potassium Concentration Gradient as a Surrogate Measure of Arterial Underfilling in Acute Decompensated Heart Failure.

Background: The monitoring of tissue hypoperfusion and the subsequent neurohumoral activation (ie, arterial underfilling) during decongestion is important for the management of acute decompensated heart failure (ADHF). The transtubular potassium concentration gradient (TTKG) has been reported to be a marker of renal aldosterone bioactivity. This study tested the hypothesis that TTKG can be a surrogate of arterial underfilling in patients with ADHF.

Quantitative Assessment of Fluid Accumulation Using Bioelectrical Impedance Analysis in Patients With Acute Decompensated Heart Failure.

Background: Acute decompensated heart failure (ADHF) is generally considered to be a problem of fluid volume overload, therefore accurately quantifying the degree of fluid accumulation is of critical importance in assessing whether adequate decongestion has been achieved. The aim of this study was to develop and validate a method to quantify the degree of fluid accumulation in patients with ADHF.

Methods and results: Using multi-frequency bioelectrical impedance analysis (BIA), we measured extracellular water (ECW) volume in 130 ADHF patients on admission and at discharge.

Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2beta and p38 MAP kinases.

Synaptic activity induces changes in the number of dendritic spines. Here, we report a pathway of regulated endocytosis triggered by arcadlin, a protocadherin induced by electroconvulsive and other excitatory stimuli in hippocampal neurons. The homophilic binding of extracellular arcadlin domains activates TAO2beta, a splice variant of the thousand and one amino acid protein kinase 2, cloned here by virtue of its binding to the arcadlin intracellular domain.