Expression Of Tight Junction Proteins Research Articles

Impact of maternal Lactiplantibacillus plantarum S58 supplementation on offspring rat immunity and gut health.

Pregnancy and lactation provide several opportunities for maternal dietary interventions to confer health benefits to newborns. However, the effects of maternal probiotic supplementation during pregnancy and lactation on offspring immunity and intestinal health remain largely unknown. This study aimed to investigate the effects of supplementation with the probiotic Lactiplantibacillus plantarum S58 (LP.S58) during pregnancy and lactation on the intestinal health and immunity of rat offspring. The results demonstrated that LP.S58 was effectively transmitted to the gastrointestinal tissues of offspring rats following maternal supplementation during pregnancy, lactation, or both, without affecting the normal development of individual organs. Furthermore, maternal LP.S58 supplementation significantly increased the serum levels of IL-4, IL-10, SOD, and T-AOC, while reducing those of TNF-α, IL-1β, IL-6, LPS, and NOS in the offspring. Additionally, it upregulated the mRNA expression of tight junction proteins and downregulated pro-inflammatory factors in the offspring rats, thereby improving intestinal health. More importantly, LP.S58 supplementation significantly increased the levels of beneficial gut bacteria, including Akkermansia and Lactobacillus, in the offspring rats. In conclusion, these findings indicate that maternal supplementation with specific probiotics during pregnancy and lactation may positively influence the immune function and intestinal development of offspring.

Ebola Virus Glycoprotein Impairs Human Retinal Pigment Epithelial Barrier Function via the PI3K/Akt-Nrf2 Pathway.

Ebola virus (EBOV) causes deadly Ebola virus disease (EVD), and EVD survivors are at high risk of developing blinding ocular complications, which associate with the breakdown of human retinal pigment epithelial (RPE) barrier. Here, we demonstrated EBOV glycoprotein (GP) could directly impair RPE barrier function. EBOV GP significantly decreased expression of tight junction (TJ) proteins in RPE monolayers, resulting in an increase of monolayer permeability. EBOV GP activated PI3K/Akt pathway and induced oxidative stress in RPE cells as evidenced by an increase in the production of reactive oxygen species (ROS), decreased expression of an antioxidant factor, nuclear factor erythroid 2-related factor 2 (Nrf2), and its downstream proteins heme oxygenase 1 (HO-1) and NAD(P)H dehydrogenase (quinone) 1 (NQO1). We found activating Nrf2 could counteract EBOV GP-induced RPE barrier injury. Furthermore, GP2 subunit is the key region in the GP that impairs RPE barrier function. Destruction of RPE barrier function by EBOV GP leads to translocation of bacteria and HIV-1. We confirmed EBOV GP-mediated impairment of RPE barrier function in mice. As an Nrf2 activator, resveratrol displays protective effects on the RPE barrier function. Collectively, our study demonstrates EBOV GP impairs the RPE barrier function through PI3K/Akt-Nrf2 pathway and resveratrol is a promising therapeutic agent for EVD-associated retinal complications.

Irisin mitigates osteoporotic-associated bone loss and gut dysbiosis in ovariectomized mice by modulating microbiota, metabolites, and intestinal barrier integrity

BackgroundOsteoporotic bone defects significantly affect patient health and quality of life. The gut-bone axis plays a crucial role in osteoporosis, and disruptions in gut microbiota are linked to systemic inflammation and compromised bone metabolism. Irisin, a myokine, has shown potential in protecting against osteoporosis, but its mechanisms of action on the gut-bone axis remain unclear. This study aimed to investigate the role of irisin in mitigating osteoporotic bone defects by examining its effects on gut microbiota, related metabolites, and intestinal barrier integrity.MethodsAn osteoporosis model was created using ovariectomized (OVX) mice. The mice were divided into Sham, OVX, and r-irisin groups. Mice in the r-irisin group received intraperitoneal injections of 100 μg/kg irisin twice weekly for five weeks. Bone parameters were analyzed by micro-CT and histological staining. Gut microbiota composition was examined via 16S rDNA sequencing. Intestinal cytokines and barrier proteins were measured using immunohistochemistry and ELISA. Fecal metabolomic profiling was conducted using liquid chromatography-tandem mass spectrometry (LC–MS/MS), and correlations between gut microbiota, metabolites, and bone metabolism markers were evaluated.ResultsIrisin treatment improved bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and trabecular number (Tb.N), and reduced trabecular separation (Tb.Sp) in OVX mice. It enhanced new bone formation and collagen deposition. Irisin restored intestinal barrier integrity by increasing tight junction protein expression and reducing inflammatory cytokines in intestinal tissues. It also modulated gut microbiota diversity, reducing Firmicutes and increasing Verrucomicrobiota abundance. Key fecal metabolites, including atractylon (r = − 0.60, P < 0.01) and enterodiol (r = + 0.83, P < 0.01), showed strong correlations with BMD.ConclusionIrisin mitigates osteoporotic bone defects by enhancing bone formation, restoring intestinal barrier integrity, modulating gut microbiota composition, and influencing fecal metabolites. These preclinical findings highlight irisin’s potential to mitigate osteoporosis via the gut-bone axis.

HFD-induced LPS translocation and elevated blood lipids exacerbated the inflammatory response in allergic rhinitis

Allergic rhinitis (AR) is one of the most prevalent chronic diseases, with studies indicating that a high-fat diet (HFD) may heighten susceptibility to AR. This study aims to investigate the impact of HFD on ovalbumin (OVA)-induced AR using both an OVA-sensitized rat model and a macrophage model treated with palmitic acid (PA). The systemic effects of HFD were explored with respect to intestinal barrier integrity, serum lipids and lipopolysaccharide (LPS) levels, and inflammatory response. In AR rats fed with HFD, there was a reduction in the expression of tight junction proteins in colon tissues, increased serum levels of lipids and LPS, and elevated inflammatory responses in both nasal lavage fluid (NLF) and serum. Additionally, there was enhanced NF-κB and NLRP3 inflammasome activity observed in both nasal and colon tissues. In vitro experiments demonstrated that PA and LPS synergistically amplified inflammatory responses in THP-1-derived macrophages, paralleling the systemic findings. These results suggest that HFD-induced intestinal barrier dysfunction facilitates the translocation of LPS into the bloodstream. Elevated serum LPS level, together with increased blood lipids levels, may exacerbate the inflammatory response in AR through the activation of NF-κB and NLRP3 inflammasome.

Six Weeks of Moderate-Intensity Treadmill Exercise Improves Intestinal Barrier and Intestinal Inflammation in Parkinson's Disease Mice.

More than 80% of patients with Parkinson's disease (PD) exhibit severe gastrointestinal symptoms, which seriously affect life quality of life. Several large-scale epidemiological studies have confirmed that exercise can improve motor symptoms of PD patients, but the influence on gastrointestinal symptoms has not been reported. To clarify whether exercise can enhance intestinal barrier and ameliorate intestinal inflammation in PD mice, we examined whether moderate-intensity treadmill exercise for 6weeks could alleviate gastrointestinal symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute PD mice. Our results demonstrated that 6weeks moderate-intensity treadmill exercise enhanced the expression of Muc-2 and tight junction proteins, while reducing the expression of cytokines and chemokines, in the distal colon. Moreover, 6weeks of treadmill exercise reduced the concentrations of short-chain fatty acids (SCFAs) and the expression of G protein-coupled receptor 43 (GPR43) to maintain the intestinal barrier and alleviate intestinal inflammation. Further data showed that 6weeks of moderate-intensity treadmill exercise enhanced insulin-like growth factor 1 (IGF-1) expression and activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Taken as a whole, these results revealed that 6weeks of moderate-intensity treadmill exercise enhanced intestinal barrier function, reduced intestinal inflammation and corrected abnormal concentrations of SCFAs by activating IGF-1/PI3K/Akt pathway in MPTP-induced subacute PD mice.

Lactobacillus paracasei Expressing Porcine Trefoil Factor 3 and Epidermal Growth Factor: A Novel Approach for Superior Mucosal Repair

Trefoil factor 3 (TFF3) and epidermal growth factor (EGF) exert a promotive effect on the functions of intestinal epithelial cells and offer protection to the intestinal mucosa. Lactobacillus paracasei can ameliorate intestinal mucosal damage. In this study, pPG-pTFF3/27-2, pPG-pEGF/27-2, and pPG-pTE/27-2 were constructed to express porcine TFF3, EGF, and a fusion protein (pTE). Functional assays showed they promoted Immortalized Porcine Enterocyte Cell line J2 (IPEC-J2) proliferation and migration, with pTE having a greater migratory effect. In dextran sulfate sodium (DSS)-induced colitis mice, oral administration of pPG-pTE/27-2 reduced colitis, improved mucosal integrity, increased the expression of tight-junction proteins and the serum level of Interleukin-10 (IL-10), and decreased the levels of pro-inflammatory Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-1β (IL-1β). These results imply that recombinant L. paracasei 27-2 strains engineered to express pTFF3 and pEGF represent a promising approach for augmenting intestinal epithelial cell function and facilitating mucosal restitution, and they possess significant potential in the treatment of intestinal mucosal injury and inflammatory bowel disease (IBD).

Effects of co-exposure to microplastics and perfluorooctanoic acid on the Caco-2 cells.

Effects of co-exposure to microplastics and perfluorooctanoic acid on the Caco-2 cells.

Current Approaches and Future Directions for the Treatment of Solid Tumour Brain Metastases

Brain metastases (BrM) are most common among patients with metastatic lung cancer, breast cancer, and melanoma. Historically, management of BrM consisted of local treatments with surgical resection and/or radiation therapy, with either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Current guidelines recommend SRS as the initial therapy for patients who have up to four BrM, but several studies have demonstrated that upfront SRS may be considered for some patients who have more than four BrM given additional clinical benefits of improved memory function and quality of life compared to WBRT. Systemic therapies are increasingly understood to cross the blood-brain barrier (BBB) following disruption of its integrity upon BrM development. Disseminated tumour cells intravasate into the circulation and spread hematogenously with a “seed and soil” tropism for the brain that provides a suitable tumour microenvironment. Tumour cells extravasate and increase the permeability of the BBB by decreasing tight junction protein expression, decreasing astrocyte pedicles, reducing pericyte coverage, and increasing neoangiogenesis. The altered integrity of the BBB allows penetration of large drug molecules, such as antibody-drug conjugates (ADCs), which exert their therapeutic effects on BrM by binding to tumour cell-specific epitopes and releasing a cytotoxic payload, even in the absence of radiation. Other therapeutic mechanisms of action include molecular (passive or receptor-mediated transport), physical (radiation or focused ultrasound), direct delivery to the brain (intrathecal or intratumoral), and cell‑mediated (immune cell extravasation) (Figure 1).

A Cascade of Microbiota-Leaky Gut-Inflammation- Is it a Key Player in Metabolic Disorders?

This review addresses critical gaps in knowledge and provides a literature overview of the molecular pathways connecting gut microbiota dysbiosis to increased intestinal permeability (commonly referred to as "leaky gut") and its contribution to metabolic disorders. Restoring a healthy gut microbiota holds significant potential for enhancing intestinal barrier function and metabolic health. These interventions offer promising therapeutic avenues for addressing leaky gut and its associated pathologies in metabolic syndrome. In metabolic disorders such as obesity and type 2 diabetes (T2D), beneficial microbes such as those producing short-chain fatty acids (SCFAs) and other key metabolites like taurine, spermidine, glutamine, and indole derivatives are reduced. Concurrently, microbes that degrade toxic metabolites such as ethanolamine also decline, while proinflammatory, lipopolysaccharide (LPS)-enriched microbes increase. These microbial shifts place a higher burden on intestinal epithelial cells, which are in closest proximity to the gut lumen, inducing detrimental changes that compromise the structural and functional integrity of the intestinal barrier. Such changes include exacerbation of tight junction protein (TJP)s dysfunction, particularly through mechanisms such as destabilization of zona occludens (Zo)-1 mRNA or post-translational modifications. Emerging therapeutic strategies including ketogenic and Mediterranean diets, as well as probiotics, prebiotics, synbiotics, and postbiotics have demonstrated efficacy in restoring beneficial microbial populations, enhancing TJP expression and function, supporting gut barrier integrity, reducing leaky gut and inflammation, and ultimately improving metabolic disorders. This review summarizes the mechanisms by which gut microbiota contribute to the development of leaky gut and inflammation associated with metabolic syndrome. It also explores strategies for restoring gut microbiota balance and functionality by promoting beneficial microbes, increasing the production of beneficial metabolites, clearing toxic metabolites, and reducing the proportion of proinflammatory microbes. These approaches can alleviate the burden on intestinal epithelial cells, reduce leaky gut and inflammation, and improve metabolic health.

Selenomethionine combined with allicin delays reactive oxidative stress-induced apoptosis, inflammation, endoplasmic reticulum stress, and barrier damage in IPEC-J2 cells via the GPX4 signaling pathway.

Selenomethionine combined with allicin delays reactive oxidative stress-induced apoptosis, inflammation, endoplasmic reticulum stress, and barrier damage in IPEC-J2 cells via the GPX4 signaling pathway.

Protective effect of Stropharia rugosoannulata polysaccharide and its derivatives on dextran sodium sulfate-induced colitis

Abstract Ulcerative colitis is a common inflammatory bowel disease. This study evaluated the protective effect and potential mechanism of Stropharia rugosoannulata polysaccharide (SP-1a) and its carboxymethylated and phosphorylated derivatives (CSP-1a and PSP-1a) against dextran sulfate sodium (DSS)-induced ulcerative colitis. The results showed that treatment with SP-1a and its derivatives alleviated the symptoms of weight loss, colon shortening, and blood in the stool induced by . SP-1a and its derivatives restore the integrity of the intestinal barrier by controlling the expression of tight junction proteins. Furthermore, they play an anti-inflammatory role by reducing oxidative stress and inhibiting the expression of pro-inflammatory factors, pro-inflammatory proteins, and nuclear factor kappa-B (NF-κB) signaling pathways. The anti-inflammatory effects of CSP-1a and PSP-1a were greater than those of SP-1a. These results indicate that SP-1a could be a potential natural medicine to protect against DSS-induced colitis.

Molecular mechanisms of the anchang group prescription in treating radiation enteritis: network pharmacology analysis and experimental evidence

BackgroundThe “Anchang” Group Prescription (ACZF), based on the traditional Bai Tou Weng Decoction and Si Jun Zi Decoction, has demonstrated clinical efficacy in alleviating symptoms of radiation enteritis (RE). Nevertheless, the precise active components and their underlying molecular mechanisms in ACZF’s effect on RE require further elucidation. This investigation seeks to delineate the active components and explore the molecular mechanisms by which ACZF mitigates RE, utilizing both network pharmacology and experimental approaches to provide a solid theoretical base for subsequent research and clinical applications.MethodsUtilizing network pharmacology, this research constructed a comprehensive “drug-active ingredient-target gene-disease” model leveraging resources such as TCMSP, SwissTargetPrediction, GeneCard, and OMIM. Cytoscape 3.8.2 along with the STRING database were instrumental in developing a protein-protein interaction (PPI) network for the identification of pivotal targets. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, were conducted via the DAVID database. Experimentally, a mouse model of RE was induced by X-ray exposure to assess the physiological and pathological responses. Parameters measured included body weight, survival rate, incidences of diarrhea, and hematochezia; histological assessments involved hematoxylin and eosin (H&amp;amp;E) and Masson’s trichrome staining to examine morphological alterations and collagen deposition in colonic tissues. Levels of cytokines such as interleukin-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor-α (TNF-α) were quantified using enzyme-linked immunosorbent assays (ELISA). Additionally, immunohistochemistry (IHC) and Western blotting (WB) were employed to evaluate the expression of tight junction proteins zonula occludens-1 (ZO-1) and claudin-1, as well as proteins linked to the PI3K/AKT pathway.ResultsKey bioactive constituents of ACZF in treating RE include quercetin, kaempferol, isorhamnetin, and luteolin, with core target proteins such as SRC, STAT3, AKT, HSP90AA1, and EGFR. Involved signaling pathways include PI3K/AKT, RAP1, and MAPK. In vivo results revealed that mice treated with ACZF showed enhanced survival, increased body weight, and extended colon lengths compared to controls. Although Masson staining showed no significant differences, H&amp;amp;E staining indicated that radiation-induced mucosal damage, including extensive ulcer formation, inflammatory cell infiltration, crypt structure destruction, and epithelial layer injury, could all be ameliorated by ACZF. Notable reductions were observed in TNF-α, IL-1β, and IL-6 levels, while IL-10 levels saw a significant rise. There was also a marked increase in the expression of ZO-1 and claudin-1. WB analyses demonstrated the activation of the PI3K/AKT pathway in RE, which was significantly curtailed by ACZF, lowering phosphorylation levels within the colonic tissues. Concurrent administration of the PI3K activator YS-49 with ACZF reversed the inhibitory effects on the PI3K/AKT pathway and mitigated impacts on epithelial TJ protein expression and inflammatory cytokine levels, highlighting the critical role of the PI3K/AKT pathway in mediating ACZF’s therapeutic effects in RE.ConclusionACZF alleviates RE by inhibiting PI3K/AKT activation, reducing inflammation, and preserving intestinal mucosal integrity.

3'-Sialyllactose and B. infantis synergistically alleviate gut inflammation and barrier dysfunction by enriching cross-feeding bacteria for short-chain fatty acid biosynthesis

ABSTRACT Ulcerative colitis (UC) poses significant threats to human health and quality of life worldwide, as it is a chronic inflammatory bowel disease. 3'-sialyllactose (3'−SL) is a key functional component of milk oligosaccharides. This study systematically evaluates the prebiotic effects of 3'-SL and its therapeutic potential in combination with Bifidobacterium infantis (B. infantis) for UC. The findings reveal that 3'-SL and B. infantis synergistically mitigate intestinal inflammation and barrier dysfunction by promoting the production of short-chain fatty acids (SCFAs) through cross-feeding mechanisms among gut microbiota. Individually, 3'-SL, B. infantis, and the synbiotic treatment all effectively alleviated UC symptoms, including reduced weight loss, improved disease activity scores, and prevention of colon shortening. Histopathological and immunofluorescence analyses further demonstrated that the synbiotic treatment significantly ameliorated colonic injury, enhanced barrier function, restored goblet cell counts, increased glycoprotein content in crypt goblet cells, and upregulated the expression of tight junction proteins (ZO-1, occludin, and claudin-1). Notably, the synbiotic treatment outperformed the individual components by better restoring gut microbiota balance, elevating SCFA levels, and modulating serum cytokine profiles, thereby reducing inflammation. These findings provide mechanistic insights into the protective effects of the synbiotic and underscore its therapeutic potential for UC and other intestinal inflammatory disorders.

Edgeworthia gardneri (Wall.) Meisn protects against HFD-induced murine atherosclerosis through improving gut microbiota-mediated intestinal barrier integrity.

Edgeworthia gardneri (Wall.) Meisn protects against HFD-induced murine atherosclerosis through improving gut microbiota-mediated intestinal barrier integrity.

Zinc Glycine supplementation improves bone quality in meat geese by modulating gut microbiota, SCFA's, and gut barrier function through Wnt10b/NF-κB axis.

Zinc Glycine supplementation improves bone quality in meat geese by modulating gut microbiota, SCFA's, and gut barrier function through Wnt10b/NF-κB axis.

Elucidating the mechanism of the first Chinese herbal formula Shuangxia Decoction to alleviate insomnia using multi-omics technologies.

Elucidating the mechanism of the first Chinese herbal formula Shuangxia Decoction to alleviate insomnia using multi-omics technologies.

Bifidobacterium bifidum postbiotics prevent Salmonella Pullorum infection in chickens by modulating pyroptosis and enhancing gut health

Bifidobacterium bifidum postbiotics prevent Salmonella Pullorum infection in chickens by modulating pyroptosis and enhancing gut health

Long term exposure to multiple environmental stressors induces mitochondrial dynamics imbalance in testis: Insights from metabolomics and transcriptomics.

Long term exposure to multiple environmental stressors induces mitochondrial dynamics imbalance in testis: Insights from metabolomics and transcriptomics.

Iota-carrageenan oligosaccharide ameliorates DSS-induced colitis in mice by mediating gut microbiota dysbiosis and modulating SCFAs-PI3K-AKT pathway.

Iota-carrageenan oligosaccharides (iCOs), derived from marine red algae, are traditionally used as antithrombotic and anti-inflammatory agents in folk medicinal practice. Despite the prevailing emphasis on these aspects in their applications, the potential of iCOs as a prebiotic agent for gut health and its subsequent impact on intestinal disorders such as colitis remains largely unexplored. A DSS-induced colitis model was employed in C57BL/6 male mice to analyze the gut microbiota via 16S rRNA sequencing. Fecal microbiota transplantation (FMT) was used to assess the therapeutic effects of iCOs on colitis. RNA sequencing (RNA-Seq) identified pathways and genes affected by iCOs. ELISA measured inflammatory cytokines, while western blot and RT-qPCR evaluated protein and gene expressions, respectively. The iCOs increased beneficial bacteria, such as Lactobacillus, Bifidobacterium, and Akkermansia. They enhanced short-chain fatty acid production and upregulated GPR41, GPR43, and GPR109A mRNA, influencing cytokine secretion. The iCOs reduced mRNA of SPHK1, BDKRB1, LCN2, and so on, potentially through PI3K-Akt pathway inhibition, and promoted tight junction protein expression. Our findings highlight the novel therapeutic potential of iCOs in colitis, indicating a multifaceted approach to treatment that includes gut microbiota modulation, intestinal barrier restoration, and the suppression of inflammatory responses.

Bupleuri Radix Ameliorates Vascular Inflammation in Human Umbilical Vein Endothelial Cells via Modulation of Tight Junction Protein Expression and Inhibition of Nuclear Factor-κB Activation.

The vascular endothelium plays a central role in the maintenance of vascular homeostasis. Inflammation of vascular endothelial cells has been closely related to the development of a wide range of cardiovascular diseases, including atherosclerosis. Bupleuri Radix (BR) possesses several biological properties, including anticancer, antimicrobial, antiviral, immunomodulatory, and anti-inflammatory properties. Furthermore, it can prevent and cure several diseases, such as the common cold, hepatitis, menoxenia, and hyperlipidemia. However, it is unclear whether BR can regulate vascular endothelial function under inflammatory conditions induced by interleukin-1β (IL-1β), a key proinflammatory cytokine. Therefore, in this study, we aimed to investigate the effect of BR on endothelial cell function using human umbilical vein endothelial cells (HUVECs) with IL-1β-induced inflammation. The effects of BR on cell migration, angiogenesis, and monocyte adhesion were determined using scratch wound-healing assay, tube-formation assay, cell adhesion assay, fluorescein isothiocyanate-dextran Transwell assay, and transepithelial electrical resistance assay. The expression of tight junction (TJ) protein and adhesion molecules was estimated using western blotting and immunofluorescence assay. The generation of reactive oxygen species was assessed using flow cytometry. BR significantly suppressed the proliferation, migration, and tube-formation ability of IL-1β-stimulated HUVECs, and the expression of adhesion molecules, especially intracellular adhesion molecule-1. BR also regulated TJ protein expression, thereby restoring the transepithelial electrical resistance value to a level comparable to that of IL-1β-treated HUVECs. Moreover, BR decreased the production of intracellular reactive oxygen species and the nuclear translocation of the nuclear factor-kappa-B p65 subunit. These findings revealed for the first time that BR prevents IL-1β-induced inflammation of blood vessel. Therefore, BR has the potential to protect the damage of vascular endothelial cells and prevent the progression of cardiovascular diseases.