Ion channel regulation of gut immunity

Mounting evidence indicates that gastrointestinal (GI) homeostasis hinges on communications among many cellular networks including the intestinal epithelium, the immune system, and both intrinsic and extrinsic nerves innervating the gut. The GI tract, especially the colon, is the home base for gut microbiome which dynamically regulates immune function. The gut\u27s immune system also provides an effective defense against harmful pathogens entering the GI tract while maintaining immune homeostasis to avoid exaggerated immune reaction to innocuous food and commensal antigens which are important causes of inflammatory disorders such as coeliac disease and inflammatory bowel diseases (IBD). Various ion channels have been detected in multiple cell types throughout the GI tract. By regulating membrane properties and intracellular biochemical signaling, ion channels play a critical role in synchronized signaling among diverse cellular components in the gut that orchestrates the GI immune response. This work focuses on the role of ion channels in immune cells, non-immune resident cells, and neuroimmune interactions in the gut at the steady state and pathological conditions. Understanding the cellular and molecular basis of ion channel signaling in these immune-related pathways and initial testing of pharmacological intervention will facilitate the development of ion channel-based therapeutic approaches for the treatment of intestinal inflammation

Asymptotically Sharp Upper Bound for the Column Subset Selection Problem

This paper investigates the spectral norm version of the column subset selection problem. Given a matrix $\mathbf{A}\in\mathbb{R}^{n\times d}$ and a positive integer $k\leq\text{rank}(\mathbf{A})$, the objective is to select exactly $k$ columns of $\mathbf{A}$ that minimize the spectral norm of the residual matrix after projecting $\mathbf{A}$ onto the space spanned by the selected columns. We use the method of interlacing polynomials introduced by Marcus-Spielman-Srivastava to derive an asymptotically sharp upper bound on the minimal approximation error, and propose a deterministic polynomial-time algorithm that achieves this error bound (up to a computational error). Furthermore, we extend our result to a column partition problem in which the columns of $\mathbf{A}$ can be partitioned into $r\geq 2$ subsets such that $\mathbf{A}$ can be well approximated by subsets from various groups. We show that the machinery of interlacing polynomials also works in this context, and establish a connection between the relevant expected characteristic polynomials and the $r$-characteristic polynomials introduced by Ravichandran and Leake. As a consequence, we prove that the columns of a rank-$d$ matrix $\mathbf{A}\in\mathbb{R}^{n\times d}$ can be partitioned into $r$ subsets $S_1,\ldots S_r$, such that the column space of $\mathbf{A}$ can be well approximated by the span of the columns in the complement of $S_i$ for each $1\leq i\leq r$

Effects of Syringic Acid on Apoptosis, Inflammation, and AKT/mTOR Signaling Pathway in Gastric Cancer Cells

Gastric cancer is one of the most common cancer and deadly disease worldwide. Despite substantial advances made in the treatment of gastric cancer, existing therapies still encounter bottlenecks. Chemotherapy, for instance, could lead to serious side effects, high drug resistance and treatment failure. Phytochemical-derived compounds from plants offer novel strategies as potent drug molecules in cancer therapy. Given the low toxicity and higher tolerance rate of naturally occurring compounds, the present study evaluated the effects of syringic acid on cytotoxicity, oxidative stress, mitochondrial membrane potential, apoptosis, and inflammatory responses in gastric cancer cell line (AGS). AGS cells were treated with various concentrations (5–40 μg/mL) of syringic acid for 24 h, after which cytotoxicity was analyzed. Reactive Oxygen Species (ROS), antioxidant enzyme activities, mitochondrial membrane potential (MMP, Δψm), cell morphologies, the expression of apoptotic markers and protein expression patterns were also investigated. Results indicated that syringic acid-treated cells developed anti-cancer activities by losing MMP, cell viability, and enhancing intracellular ROS. Syringic acid selectively developed apoptosis in a dose-dependent manner via enhanced regulation of caspase-3, caspase-9 and Poly ADP-ribose Polymerase (PARP) whereas decreasing the expression levels of p53 and BCL-2. Syringic acid also lowered activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) whereas Thio Barbituric Acid Reactive Substances (TBARS) increased. Syringic acid suppressed gastric cancer cell proliferation, inflammation, and induced apoptosis by upregulating mTOR via AKT signaling pathway. The study suggests syringic acid may constitute a promising chemotherapeutic candidate for gastric cancer treatment. Our study is the first report on the anti-cancer effects of syringic acid against gastric cancer cells via apoptosis, inhibition of inflammation, and the suppression of the mTOR/AKT signaling pathway

The role of VdSti1 in Verticillium dahliae: insights into pathogenicity and stress responses

Sti1/Hop, a stress-induced co-chaperone protein, serves as a crucial link between Hsp70 and Hsp90 during cellular stress responses. Despite its importance in stress defense mechanisms, the biological role of Sti1 in Verticillium dahliae, a destructive fungal pathogen, remains largely unexplored. This study focused on identifying and characterizing Sti1 homologues in V. dahliae by comparing them to those found in Saccharomyces cerevisiae. The results indicated that the VdSti1-deficient mutant displayed increased sensitivity to drugs targeting the ergosterol synthesis pathway, leading to a notable inhibition of ergosterol biosynthesis. Moreover, the mutant exhibited reduced production of microsclerotia and melanin, accompanied by decreased expression of microsclerotia and melanin-related genes VDH1, Vayg1, and VaflM. Additionally, the mutant’s conidia showed more severe damage under heat shock conditions and displayed growth defects under various stressors such as temperature, SDS, and CR stress, as well as increased sensitivity to H2O2, while osmotic stress did not impact its growth. Importantly, the VdSti1-deficient mutant demonstrated significantly diminished pathogenicity compared to the wild-type strain. This study sheds light on the functional conservation and divergence of Sti1 homologues in fungal biology and underscores the critical role of VdSti1 in microsclerotia development, stress response, and pathogenicity of V. dahliae

Modification of neurogenic colonic motor behaviours by chemogenetic ablation of calretinin neurons

How the enteric nervous system determines the pacing and propagation direction of neurogenic contractions along the colon remains largely unknown. We used a chemogenetic strategy to ablate enteric neurons expressing calretinin (CAL). Mice expressing human diphtheria toxin receptor (DTR) in CAL neurons were generated by crossin