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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. Notably, an octapeptide (VPAGVAHW) from the hydrolysate demonstrated significant antioxidant activity, particularly against oxidative stress induced by iodoacetic acid (IAA) or hydrogen peroxide (H2O2) and ER stress caused by tunicamycin (TM) in L929 cells. This peptide's effectiveness was evident in its dose-dependent ability to enhance cell viability and mitigate stress effects, although its efficiency varied with the stress inducer. Our study suggests that Riceberry™-derived peptides could serve as a promising natural antioxidant with potential benefits for health promotion and applications in the food industry, offering an environmentally friendly alternative to synthetic antioxidants. [ABSTRACT FROM AUTHOR]

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. We sought to define the impact of claudin-2 channels on disease. Transgenic claudin-2 overexpression or IL-13-induced claudin-2 upregulation increased intestinal small cation permeability in vivo. IL-13 did not, however, affect permeability in claudin-2-knockout mice. Claudin-2 is therefore necessary and sufficient to effect size- and charge-selective permeability increases in vivo. In chronic disease, T cell transfer colitis severity was augmented or diminished in claudin-2-transgenic or -knockout mice, respectively. We translated the in vitro observation that casein kinase-2 (CK2) inhibition blocks claudin-2 channel function to prevent acute, IL-13-induced, claudin-2-mediated permeability increases in vivo. In chronic immune-mediated colitis, CK2 inhibition attenuated progression in claudin-2-sufficient, but not claudin-2-knockout, mice, i.e., the effect was claudin-2 dependent. Paracellular flux mediated by claudin-2 channels can therefore promote immune-mediated colitis progression. Although the mechanisms by which claudin-2 channels intensify disease remain to be defined, these data suggest that claudin-2 may be an accessible target in immune-mediated disorders, including inflammatory bowel disease., Introduction Barriers that define distinct tissue compartments and separate self from non-self are necessary for survival of multicellular organisms. In some organs, for example the integument and bladder, the barrier [...]

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. Therefore, inhibition of MMP-7 enzymatic activity can be a therapeutic strategy for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Introduction: Stress disturbs the gut-brain axis and contributes to the development of mood disorders and memory impairment. Recent findings on the anti-stress effects of monoamine modulators have shown that the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine (Vlx) is more effective in stressed rodents. However, the effects of Vlx on microbiota and memory impairment- and stress-related behaviors are still unknown. Synbiotics (Syn), a mixture of probiotics and prebiotics, can modify the gut microbiome; however, the effects of anti-anxiety and anti-memory deficits are still not well understood. Therefore, this study proposed to compare the effectiveness of Vlx and Syn in the reduction of learned fearand memory impairment-like behaviors in an animal model of stress. Methods: Forty male adult Wistar rats were subjected to stress by immobilization in a restrainer for 2h per day and were administered 10mg/kg Vlx and/or 2g of Syn containing 1.0x1010 CFU probiotic strains and prebiotic oligosaccharides daily for 14 days. Learned fear, recognition memory and locomotor activity were evaluated by the elevated-T maze, novel objective recognition and open field tests. Blood samples and adrenal glands were collected to measure the circulating corticosterone levels and relative adrenal weights, which were used as markers of stress responses. Results: The immobilized-stressed rats showed hyperactivity in stress responses, as demonstrated by increased relative adrenal weights and serum corticosterone levels. Both Vlx and Syn reduced the increase in serum corticosterone levels in stressed rats. Furthermore, Vlx- and/or Syn-treated stressed rats had fewer learned fear-like behaviors and a higher discrimination index without any locomotor activity changes than vehicle-treated stressed rats. Conclusion: Syn supplementation had comparable effects to SNRIs in alleviating the risk of developing anxiety disorders and memory impairment in stressed individuals or psychiatric patients. [ABSTRACT FROM AUTHOR]

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. In fact, intestinal tight junctions that seal the paracellular space can restrict mucosal-to-serosal transport of hostile luminal contents. Tight junctions can form both an absolute barrier and a paracellular ion channel. Although defective tight junctions potentially lead to compromised intestinal barrier and the development and progression of gastrointestinal (GI) diseases, no FDA-approved therapies that recover the epithelial tight junction barrier are currently available in clinical practice. Here, we discuss the impacts and regulatory mechanisms of tight junction disruption in the gut and related diseases. We also provide an overview of potential therapeutic targets to restore the epithelial tight junction barrier in the GI tract. [ABSTRACT FROM AUTHOR]

Cholera is caused by infection with Vibrio cholerae. This study aimed to investigate the pathophysiology of diarrhea caused by the V. cholerae O1 El Tor variant (EL), a major epidemic strain causing severe diarrhea in several regions. In the ligated ileal loop model of EL-induced diarrhea in the ICR mice, a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor and a calciumactivated chloride channel (CaCC) inhibitor similarly inhibited intestinal fluid secretion. In addition, barrier disruption and NF-κB-mediated inflammatory responses, e.g., iNOS and COX-2 expression, were observed in the infected ileal loops. Interestingly, intestinal fluid secretion and barrier disruption were suppressed by NF-κB and COX-2 inhibitors, whereas an iNOS inhibitor suppressed barrier disruption without affecting fluid secretion. Furthermore, EP2 and EP4 PGE2 receptor antagonists ameliorated the fluid secretion in the infected ileal loops. The amount of cholera toxin (CT) produced in the ileal loops by the EL was ~2.4-fold of the classical biotype. The CT transcription inhibitor virstatin, a toll-like receptor-4 (TLR-4) antibody and a CT antibody suppressed the ELinduced intestinal fluid secretion, barrier disruption and COX-2 expression. The CT at levels detected during EL infection induced mild intestinal barrier disruption without inducing inflammatory responses in mouse intestine. Collectively, this study indicates that CT-induced intestinal barrier disruption and subsequent TLR-4-NF-κB-mediated COX-2 expression are involved in the pathogenesis of EL-induced diarrhea and represent promising novel therapeutic targets of cholera. [ABSTRACT FROM AUTHOR]

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 2+ concentration affects tight junction assembly. Therefore, the removal and re-addition of Ca 2+ into cell culture medium of cultured intestinal epithelial cells causes destabilization and reassembly of tight junction to membrane periphery near apical surface, respectively. Based on this principle, the Ca 2+ -switch assay was established to investigate tight junction assembly in fully differentiated intestinal epithelial cells. This chapter provides a stepwise protocol for culture of intestinal epithelial cell monolayers using T84 cell line as an in vitro model and the Ca 2+ -switch assay for evaluating tight junction assembly.