Protective Effects of an Octapeptide Identified from Riceberry™ () Protein Hydrolysate on Oxidative and Endoplasmic Reticulum (ER) Stress in L929 Cells.

Reactive oxygen species (ROS) play a critical role in oxidative stress and cellular damage, underscoring the importance of identifying potent antioxidants. This research focuses on the antioxidant capabilities of Riceberry™-derived peptides and their protective effects against oxidative and endoplasmic reticulum (ER) stress in L929 cells. By simulating human digestion, Riceberry™ protein hydrolysate was generated, from which antioxidant peptides were isolated using OFFGEL electrophoresis and LC-MS/MS.

Solanum melongena L. Extract Promotes Intestinal Tight Junction Re-Assembly via SIRT-1-Dependent Mechanisms.

Tight junction disruption can lead to pathogenesis of various diseases without therapeutic strategy to recover intestinal barrier integrity. The main objective of this study is to demonstrate the effect of Solanum melongena L. extract (SMLE) on intestinal tight junction recovery and its underlying mechanism.

Inter-claudin antagonism of paracellular pore function: mechanism and beyond.

Claudin-2-dependent pore function mediates paracellular cation permeability and can result in pathogenesis of many diseases. Although existing various types of claudins, including barrier-forming and pore-forming claudins, their heterodimeric interaction affecting barrier and pore functions has never been fully elucidated yet. Recently, Shashikanth and colleagues demonstrated that expression of claudin-4 was able to antagonize paracellular pore activity of claudin-2.

Discovery of Fungus-Derived Nornidulin as a Novel TMEM16A Inhibitor: A Potential Therapy to Inhibit Mucus Secretion in Asthma.

Introduction: Inhibition of Ca-activated transmembrane protein 16A (TMEM16A) Cl channels has been proposed to alleviate mucus secretion in asthma. In this study, we identified a novel class of TMEM16A inhibitors from natural sources in airway epithelial Calu-3 cells and determine anti-asthmatic efficacy of the most potent candidate in a mouse model of asthma.

Methods: For electrophysiological analyses, IL-4-primed Calu-3 cell monolayers were mounted in Ussing chamber and treated with various fungus-derived depsidones prior to the addition of UTP, ionomycin, thapsigargin, or E to stimulate TMEM16A Cl current.

Matrix metalloproteinase-7 and claudin-7 as novel identified therapeutic targets for restoration of intestinal epithelial barrier in inflammatory bowel diseases.

Intestinal tight junction disruption and mucosal immune dysregulation contribute to pathogenesis and progression of inflammatory bowel diseases (IBD). A proteolytic enzyme matrix metalloproteinase 7 (MMP-7), which is highly expressed in intestinal tissue, is implicated to IBD and other immune overactivation-associated diseases. In the issue of the Frontiers in Immunology, Ying Xiao and colleagues demonstrate that MMP-7-mediated claudin-7 degradation promotes IBD pathogenesis and disease progression.

Butylene Glycol Used as a Sustainable Solvent for Extracting Bioactive Compounds from Flowers with Ultrasound-Assisted Extraction.

The research aims to assess the yield of bioactive compounds and their antioxidant activities obtained from tea flowers using an ultrasound-assisted extraction method with butylene glycol (BG-UAE) through Box-Behnken design. It investigates the bioactive compounds including the total phenolic content (TPC), total flavonoid content (TFC), and total tannin content (TTC) and analyzes their antioxidant activities, bioactive compound composition by liquid chromatography triple quadrupole tandem mass spectrometry, and their cellular activities via UAE and maceration using BG or ethanol as the solvent. Under optimal conditions, the values of the TPC, TFC, TTC, 1,1-diphenyl-2-picrylhydrazil radical scavenging assay, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical scavenging assay, and ferric reducing antioxidant power assay (FRAP) of the BG-UAE extract were 54.

Relief Effects of Icariin on Inflammation-Induced Decrease of Tight Junctions in Intestinal Epithelial Cells.

Inflammatory cytokines including TNF-α and IL-1β impair intestinal barrier function in aging by disrupting intestinal tight junction integrity. Icariin (ICA) has a variety of pharmacological effects. Indeed, ICA produces anti-inflammatory, anti-oxidative stress, and inhibitory effects on microRNA (miRNA) expression.

Tight junctions: from molecules to gastrointestinal diseases.

Intestinal epithelium functions as a tissue barrier to prevent interaction between the internal compartment and the external milieu. Intestinal barrier function also determines epithelial polarity for the absorption of nutrients and the secretion of waste products. These vital functions require strong integrity of tight junction proteins.

β-eudesmol but not atractylodin exerts an inhibitory effect on CFTR-mediated chloride transport in human intestinal epithelial cells.

Oriental herbal medicine with the two bioactive constituents, β-eudesmol (BE) and atractylodin (AT), has been used as a remedy for gastrointestinal disorders. There was no scientific evidence reporting their antidiarrheal effect and underpinning mechanisms. Therefore, we aimed to investigate the anti-secretory activity of these two compounds in vitro.

Electrophysiologic Analysis of Tight Junction Size and Charge Selectivity.

Tight junctions form selectively permeable barriers that limit paracellular flux across epithelial-lined surfaces. Rather than being absolute barriers, tight junctions in many tissues allow ions, water, and other small molecules to cross on the basis of size and charge selectivity via the high-capacity pore pathway. Most probes currently used to assess tight junction permeability exceed the maximum size capacity of the pore pathway.

Establishment of Intestinal Epithelial Cell Monolayers and Their Use in Calcium Switch Assay for Assessment of Intestinal Tight Junction Assembly.

Intestinal barrier function relies primarily on the assembly and integrity of tight junctions, which forms a size-selective barrier. This barrier restricts paracellular movement of solutes in various types of epithelia. Of note, extracellular Ca concentration affects tight junction assembly.

Culture of Intestinal Epithelial Cell Monolayers and Their Use in Multiplex Macromolecular Permeability Assays for In Vitro Analysis of Tight Junction Size Selectivity.

Tight junctions form a selectively permeable barrier that limits paracellular flux across epithelial-lined surfaces. Small molecules (less than ∼8 Å diameter) can traverse the junction via the size- and charge-selective, high-conductance pore pathway. In contrast, the low-conductance leak pathway accommodates larger macromolecules (up to ∼100 Å diameter) and is not charge-selective.

Myosin light chain kinase is a potential target for hypopharyngeal cancer treatment.

Hypopharyngeal cancer is squamous cell carcinoma (SCC) with the worst prognosis among the head and neck cancers. Overall, the 5-year survival rate remains poor although diagnostic imaging, radiation, chemotherapy, and surgical techniques have been improved. The mortality of patients with hypopharyngeal cancer is partly due to an increased likelihood of developing a second primary malignancy and metastasis.

A prebiotic fructo-oligosaccharide promotes tight junction assembly in intestinal epithelial cells via an AMPK-dependent pathway.

Tight junctions play an important role in maintaining barrier integrity of intestinal epithelia. Activation of AMP-activated protein kinase (AMPK) promotes tight junction assembly in intestinal epithelial cells (IEC). Fructo-oligosaccharides (FOS), well-known prebiotics, have previously been shown to alleviate inflammation-associated intestinal epithelial disruption although the mechanisms were unclear.

Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice.

The tight junction protein claudin-2 is upregulated in disease. Although many studies have linked intestinal barrier loss to local and systemic disease, these have relied on macromolecular probes. In vitro analyses show, however, that these probes cannot be accommodated by size- and charge-selective claudin-2 channels.

A G-protein coupled receptor 39 agonist stimulates proliferation of keratinocytes via an ERK-dependent pathway.

Keratinocyte proliferation serves as a crucial process in skin wound healing. The zinc-sensing G-protein coupled receptor 39 (GPR39), which is highly expressed in keratinocytes, has been shown to promote skin wound healing. The aim of this study was to investigate the effect of GPR39 activation on proliferation of keratinocytes and its underlying mechanism using immortalized human keratinocytes (HaCaT) as an in vitro model.

Fructo-oligosaccharides alleviate inflammation-associated apoptosis of GLP-1 secreting L cells via inhibition of iNOS and cleaved caspase-3 expression.

Glucagon-like peptide 1 (GLP-1) released from enteroendocrine (L) cells regulates insulin secretion. Intestinal inflammation and impaired GLP-1 release have been found in type 2 diabetes mellitus (T2DM) patients. Fructo-oligosaccharides (FOS), a known prebiotic, improve GLP-1 release and glucose homeostasis in T2DM models.

Galactomannan Pentasaccharide Produced from Copra Meal Enhances Tight Junction Integration of Epithelial Tissue through Activation of AMPK.

Mannan oligosaccharide (MOS) is well-known as an effective fed supplement for livestock to increase their nutrients absorption and health status. Pentasaccharide of mannan (MOS5) was reported as a molecule that possesses the ability to increase tight junction of epithelial tissue, but the structure and mechanism of action remains undetermined. In this study, the mechanism of action and structure of MOS5 were investigated.

Activation of constitutive androstane receptor inhibits intestinal CFTR-mediated chloride transport.

Constitutive androstane receptor (CAR) belonging to the nuclear receptor superfamily plays an important role in the xenobiotic metabolism and disposition. It has been reported that CAR regulates the expression of the ATP-binding cassette (ABC) transporters in the intestine, such as multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 2/3 (MRP2 and MRP3). In this study, we investigated the role of CAR in the regulation of cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride transport in T84 human colonic epithelial cells and mouse intestinal tissues.

An agonist of a zinc-sensing receptor GPR39 enhances tight junction assembly in intestinal epithelial cells via an AMPK-dependent mechanism.

Intestinal barrier function depends on integrity of tight junctions, which serve as barriers to transepithelial influx of noxious substances/microorganisms from gut lumen. The G-protein coupled receptor 39 (GPR39) is a zinc-sensing receptor, which is expressed in several cell types including intestinal epithelial cells (IECs). The main objective of this study was to investigate the effect of GPR39 activation on tight junction assembly in IECs.

Cellular mechanisms underlying the inhibitory effect of flufenamic acid on chloride secretion in human intestinal epithelial cells.

Intestinal Cl secretion is involved in the pathogenesis of secretory diarrheas including cholera. We recently demonstrated that flufenamic acid (FFA) suppressed Vibrio cholerae El Tor variant-induced intestinal fluid secretion via mechanisms involving AMPK activation and NF-κB-suppression. The present study aimed to investigate the effect of FFA on transepithelial Cl secretion in human intestinal epithelial (T84) cells.

Fatty acid and mineral receptors as drug targets for gastrointestinal disorders.

Nutrient-sensing receptors, including fatty acid receptors (FFA1-FFA4), Ca-sensing receptors and Zn-sensing receptors, are involved in several biological processes. These receptors are abundantly expressed in the GI tract, where they have been shown to play crucial roles in regulating GI function. This review provides an overview of the GI functions of fatty acid and mineral receptors, including the regulation of gastric and enteroendocrine functions, GI motility, ion transport and cell growth.

Flufenamic acid protects against intestinal fluid secretion and barrier leakage in a mouse model of Vibrio cholerae infection through NF-κB inhibition and AMPK activation.

Nuclear factor kappa B (NF-κB)-mediated inflammatory responses play crucial roles in the pathogenesis of diarrhea caused by the Vibrio cholerae El Tor variant (EL), which is a major bacterial strain causing recent cholera outbreaks. Flufenamic acid (FFA) has previously been demonstrated to be a potent activator of AMP-activated protein kinase (AMPK), which is a negative regulator of NF-κB signaling. This study aimed to investigate the anti-diarrheal efficacy of FFA in a mouse model of EL infection and to investigate the mechanisms by which FFA activates AMPK in intestinal epithelial cells (IEC).