Expression Levels Of E-cadherin Research Articles

3,5,6,7,8,3’,4’- Heptamethoxyflavonoid inhibits TGF-β1-induced epithelial–mesenchymal transition by regulating oxidative stress and autophagy through MEK/ERK/PI3K/AKT/mTOR signaling pathway

Epithelial–mesenchymal transition (EMT) is a crucial pathological process in the pathogenesis of fibrosis. 3,5,6,7,8,3′,4′-hepmethoxyflavone (HMF), the main active ingredient extracted from the Chinese herb Breynia fruticosa (L.) Hook. f., has been shown to have beneficial effects on regulating apoptosis and inhibiting collagen deposition. However, it remains unclear whether and how HMF alleviates transforming growth factor-β1 (TGF-β1)-induced EMT. The objective of this study was to investigate the impact of HMF on TGF-β1-induced EMT in human alveolar Type II epithelial cells (A549) and its underlying mechanism. In vitro culture of TGF-β1-induced EMT in A549 cells revealed that HMF reduced cell viability and migration, inhibited collagen deposition, decreased expression levels of mesenchymal cell markers and fibrosis markers α-SMA, MMP2, TIMP1, β-catenin, and Snail. Meanwhile, the expression level of E-cadherin increased as an epithelial cell marker. Additionally, we discussed the effects of HMF on oxidative stress and autophagy. Various experiments confirmed that HMF regulated the expression levels of Nrf2, keap-1, HO-1, ROS, MDA, SOD, GSH, and played a role in reducing oxidative stress. At the same time, HMF significantly activated autophagy by increasing expressions of Beclin-1 and LC3B as well as enhancing autophagosome content. The addition 3-MA, an autophagy inhibitor attenuated these beneficial effects. Furthermore, HMF significantly inhibited phosphorylation levels of MEK, ERK, PI3K, AKT, and mTOR through various pathways. In conclusion, HMF effectively inhibits TGF-β1-induced EMT in A549 cells by targeting the MEK/ERK/PI3K/AKT/mTOR signaling pathway. Moreover, it exhibits a close correlation with the suppression of oxidative stress and induction of autophagy.

Photobiomodulation inhibits retinal degeneration in diabetic mice through modulation of stem cell mobilization and gene expression.

The number of people suffering from type 2 diabetes (DM2) is increasing and over 30 percent of DM2 patients will develop diabetic retinopathy (DR). Available therapeutic approaches for DR have their limitations. It is of great significance to search for other effective alternate therapeutic approaches. The present study aimed to explore the beneficial effects of photobiomodulation (PBM) on the diabetic retinopathy and underlying mechanisms. Streptozotocin was administered to male mice to establish diabetic model. The mice in the diabetic group (DM) received no treatment, and the mice in DM+PBM group received LED illumination (wavelength 670nm) once a day for 20 consecutive weeks. Retinal vessel degenerate changes, the expression levels of E-Cadherin, N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α in retina, the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 were determined. PBM could significantly inhibit the degenerative change of diabetic retinal vessels, decrease the expression levels of E-Cadherin and N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α and increase VEGF mRNA levels in retina. PBM could also increase the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 in diabetic mice. PBM at 4min/day for 20 consecutive weeks significantly inhibit the degenerative change of diabetic retinal vessels, and PBM is likely to produce its beneficial effects on the retina through promoting the migration of bone marrow stem cells to circulation and diabetic retinal tissue. The present study provides a new therapeutic direction and experimental foundation for the treatment of diabetic retinopathy.

Integrating E-cadherin expression levels with TNM staging for enhanced prognostic prediction in colorectal cancer patients

PurposeThis study aimed to investigate the clinical significance of E-cadherin expression levels in colorectal cancer tissues and explore the relationship between E-cadherin expression and tumor node metastasis (TNM) stage. The goal was to establish a more accurate prognostic prediction for colorectal cancer patients by analyzing E-cadherin expression levels alongside TNM staging.MethodsThe study examined colorectal cancer patients by dividing them into groups based on E-cadherin expression levels. It then assessed their 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs). Additionally, the prognosis of patients was analyzed by combining E-cadherin expression levels with TNM staging, particularly focusing on patients in stages III and IV.ResultsThe E-cadherinLow group had significantly worse outcomes, with HRs of 2.30 for EFS and 2.76 for DSS compared to the E-cadherinHigh group. When combined with TNM stage III/IV, patients with E-cadherinLow expression showed a poor prognosis, with HRs of 1.93 for EFS and 2.35 for DSS compared to those with E-cadherinHigh expression at the same TNM stage.ConclusionsLow levels of E-cadherin expression are associated with a poor prognosis and decreased survival in colorectal cancer patients. Combining E-cadherin expression levels with TNM staging provides a more precise prediction of patient prognosis and survival, potentially guiding personalized treatment strategies.

Mesua ferrea L. extract inhibits cell invasion and tumor growth in breast cancer in vitro and in vivo.

Mesua ferrea L. was commonly used in Uyghur medicine, and the flowering buds of M. ferrea extract exhibited significant inhibitory effects on the proliferation of breast cancer cells in our preliminary research; however, the underlying active components remain to be elucidated. In this study, firstly, we extracted the flowering buds of M. ferrea with methanol and obtained eleven bioactive sub-fractions (MF-P-1-MF-P-11), and MF-P-5 showed the strongest inhibitory activity against MDA-MB-231 and 4T1 cells. Subsequently, 52 compounds from MF-P-5 were identified by UPLCQ-TOFMS/MS. In addition, ten compounds (MF1-MF10) from MF-P-5 were separated and identified, and MF5 could inhibit MDA-MB-231 and 4T1 cells proliferation as MTT and colony formation assay, suppress the migration of MDA-MB-231 and 4T1 cells by means of wound healing assay, reduce the expression level of E-cadherin, and induce MDA-MB-231 and 4T1 cells apoptosis by Annexin V-FITC/PI double staining assay and up-regulate the expression of Bax and down-regulate the expression of PARP. Ultimately, we evaluated the effects of MF-P-5 on breast cancer via MDA-MB-231 cell xenograft in nude mice. The results of tumor volume and weight and immunohistochemistry revealed that MF-P-5 could significantly inhibit the growth of MDA-MB-231 cells in vivo. Besides, the expression levels of E-cadherin significantly increased and MMP-2 decreased. The above results suggested that MF-P-5 could suppress the invasion of breast cancer cells in vivo. Furthermore, the expression level of Bcl-2 was prominently reduced which revealed that MF-P-5 stimulated the mitochondrial apoptosis pathway in vivo. As a result, MF5 could inhibit MDA-MB-231 and 4T1 cells proliferation, migration and tumor growth in vitro and MF-P-5 could suppress tumor growth in vivo which had laid a theoretical foundation for further clinical application.

Tumor Microenvironment Responsive Key Nanomicelles for Effective Against Invasion and Metastasis in Ovarian Cancer Using Mice Model.

Ovarian cancer is difficult to detect in its early stages, and it has a high potential for invasion and metastasis, along with a high rate of recurrence. These factors contribute to the poor prognosis and reduced survival times for patients with this disease. The effectiveness of conventional chemoradiotherapy remains limited. Nano-particles, as a novel drug delivery system, have significant potential for improving therapeutic efficacy and overcoming these challenges. According to the high expression level of matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment, MMP-2 responsive nano-particles (PVGLIG-MTX-D/T-NMs) containing docetaxel and triptolide were prepared by the thin-film dispersion method. The synergistic effect between docetaxel and triptolide was systematically investigated, the ratio of the two drugs was optimized, and the physicochemical properties of the nano-particles and their ability to inhibit ovarian cancer cell growth and metastasis were evaluated in vitro and in vivo. PVGLIG-MTX-D/T-NMs enhanced the targeting, stability, and bioavailability of the drug, while reducing the dose and toxicity. In addition, by regulating the expression levels of E-Cadherin, N-Cadherin, matrix metalloproteinases (MMPs), hypoxia-inducible factor 1-alpha (HIF-1α), and vascular endothelial growth factor (VEGF), it exhibited an inhibitory effect on epithelial-mesenchymal transformation (EMT) and tumor cell angiogenesis, and effectively inhibited the invasion and metastasis of ovarian cancer cells. PVGLIG-MTX-D/T-NMs achieved passive targeting of tumor sites by enhancing permeability and retention (EPR) effects. Subsequently, the uptake of the drug by tumor cells was enhanced by MMP-2 responsiveness and the modification of methotrexate targeting ligands. By regulating the expression levels of invasion- and metastasis-related proteins in tumor tissues, the nano-particles affected the EMT process, inhibited tumor angiogenesis, and suppressed the malignant potential of invasion and metastasis in ovarian cancer. These findings provided a new direction for further exploration of tumor-targeted therapy.

Stem Cells Within Three-Dimensional-Printed Scaffolds Facilitate Airway Mucosa and Bone Regeneration and Reconstruction of Maxillary Defects in Rabbits.

Background and Objectives: Current craniofacial reconstruction surgical methods have limitations because they involve facial deformation. The craniofacial region includes many areas where the mucosa, exposed to air, is closely adjacent to bone, with the maxilla being a prominent example of this structure. Therefore, this study explored whether human neural-crest-derived stem cells (hNTSCs) aid bone and airway mucosal regeneration during craniofacial reconstruction using a rabbit model. Materials and Methods: hNTSCs were induced to differentiate into either mucosal epithelial or osteogenic cells in vitro. hNTSCs were seeded into polycaprolactone scaffold (three-dimensionally printed) that were implanted into rabbits with maxillary defects. Four weeks later, tissue regeneration was analyzed via histological evaluation and immunofluorescence staining. Results: In vitro, hNTSCs differentiated into both mucosal epithelial and osteogenic cells. hNTSC differentiation into respiratory epithelial cells was confirmed by Alcian Blue staining, cilia in SEM, and increased expression levels of FOXJ1 and E-cadherin through quantitative RT-PCR. hNTSC differentiation into bone was confirmed by Alizarin Red staining, increased mRNA expression levels of BMP2 (6.1-fold) and RUNX2 (2.3-fold) in the hNTSC group compared to the control. Four weeks post-transplantation, the rabbit maxilla was harvested, and H&E, SEM, and immunohistofluorescence staining were performed. H&E staining and SEM showed that new tissue and cilia around the maxillary defect were more prominent in the hNTSC group. Also, the hNTSCs group showed positive immunohistofluorescence staining for acetylated α-tubulin and cytokerin-5 compared to the control group. Conclusions: hNTSCs combined with PCL scaffold enhanced the regeneration of mucosal tissue and bone in vitro and promoted mucosal tissue regeneration in the in vivo rabbit model.

PTEN inhibits epithelial mesenchymal transition of thyroid cancer cells by regulating the Wnt/β-Catenin signaling pathway

ObjectiveThe global incidence of thyroid cancer (THCA) has significantly risen in recent years. This study aims to investigate the role and mechanisms of PTEN in epithelial mesenchymal transition (EMT), invasion and migration of THCA cells.MethodsPTEN expression in THCA was analyzed through bioinformatics databases. RT-qPCR and Western blot analyses were performed to quantify PTEN levels in the Nthy-ori 3–1 cell line and three THCA cell types (TPC-1, B-CPAP, FTC-133). TPC-1 cells were transfected with a PTEN overexpression plasmid and treated with the Wnt activator. Cell viability and apoptosis were assessed via CCK-8 and flow cytometry, respectively. The expression levels of E-Cadherin, N-Cadherin, and Vimentin in TPC-1 cells were evaluated using Western blot. The invasive, migratory, and wound-healing abilities of the cells were examined using Transwell and scratch assays. Activation of the Wnt/β-catenin pathway was assessed through Western blot.ResultsPTEN expression was significantly lower in THCA cells, particularly in TPC-1 cells compared to other cell lines. PTEN overexpression led to decreased viability in TPC-1 cells, increased apoptosis, and a rise in E-Cadherin levels while reducing N-Cadherin and Vimentin levels, thereby inhibiting EMT. Furthermore, PTEN overexpression diminished the invasive, migratory and wound-healing capabilities of TPC-1 cells and suppressed activation of the Wnt/β-catenin pathway. Treatment with the Wnt activator partially counteracted the effects of PTEN overexpression on TPC-1 cells.ConclusionPTEN functions to inhibit EMT and the invasive and migratory characteristics of THCA cells by blocking the activation of the Wnt/β-catenin pathway.

SIRT1 Activation Suppresses Corneal Endothelial-Mesenchymal Transition via the TGF-β/Smad2/3 Pathway.

Endothelial-mesenchymal transition (EnMT) is the transversion of endothelial cells to mesenchymal cells under certain physiological or pathological conditions. When EnMT occurs in the corneal endothelium, corneal endothelial cells (CECs) lose their normal function and thus cannot maintain corneal clarity. Studies have shown that the mechanism of EnMT in CECs involves the transforming growth factor-β (TGF-β) signaling pathway, and one of the important inhibitors of the TGF-β/Smad2/3 pathway is sirtuin-1 (SIRT1). In this study, we used a rat model of corneal endothelium injury and TGF-β1-treated human CECs to induce EnMT, aiming to explore whether SIRT1 activation inhibits corneal EnMT in vivo and in vitro. SIRT1 was activated and suppressed using resveratrol (RSV) and EX527, respectively. The endothelial markers and mesenchymal markers were measured by immunofluorescence and Western blot assays. Co-immunoprecipitation was used to detect the interaction between SIRT1 and Smad2/3. The results showed that after mechanical injury, the group treated with RSV-activated SIRT1 regained corneal transparency and recovered from edema faster than the control group. Moreover, RSV-activated SIRT1 downregulated the expression levels of alpha smooth muscle actin (α-SMA), vimentin, and Snail and upregulated the expression levels of E-cadherin and Na+/K+-ATPase both in vivo and in vitro, but these effects were reversed when SIRT1 was inhibited by EX527. SIRT1 also upregulated the expression levels of TGF-β receptor 1 and phosphorylated Smad2/3. The interaction between SIRT1 and Smad2/3 in vitro was confirmed by co-immunoprecipitation. Overall, our results indicate that SIRT1 activation inhibits corneal EnMT via the TGF-β/Smad2/3 pathway, which may be a potential therapeutic target for corneal endothelium dysfunction.

Effect of silencing Ras homolog family member C on proliferation, invasion, and migration of salivary adenoid cystic carcinoma.

This study aimed to investigate the effects of silencing Ras homolog family member C (RhoC) on the proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) of salivary adenoid cystic carcinoma (SACC) and its molecular mechanisms. A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1, 2019 to March 1, 2024 were selected, and the expression levels of RhoC were detected by Western blot and immunohistochemistry. Three small interfering RNA (siRNAs) were designed to target the RhoC gene sequence, transfected into SACC-LM and SACC-83 cell lines, and evaluated for transfection efficiency. The protein expression levels of RhoC, Rho-associated protein kinase-1 (ROCK1), p38 mitogen-activated protein kinase (p38MAPK), phosphorylated-p38MAPK (p-p38MAPK), twist family bHLH transcription factor 1 (TWIST1), E-cadherin, N-cadherin, and Vimentin were compared using Western blot. CCK-8 assay, flow cytometry, transwell invasion assay, and wound healing assay were conducted to assess the differences in cell proliferation, apoptosis, invasion, and migration abilities among the groups. Bioinformatics methods were also used to predict possible upstream micro RNAs (miRNAs) of RhoC and their expression levels in SACC. Moreover, dual-luciferase reporter gene experiments were performed to verify the binding sites of miR-138-5p and RhoC. RhoC was highly expressed in SACC (P<0.05). After silencing RhoC, the test group showed a significant decrease in the expression level of ROCK1, p-p38MAPK, TWIST1, N-cadherin, and Vimentin, as well as a significant increase in the expression level of E-cadherin (P<0.05). No significant difference in the expression level of p38MAPK was observed (P>0.05). The cell proliferation, invasion, and migration ability decreased in the test group, whereas the apoptosis rates significantly increased (P<0.05). miR-138-5p was lowly expressed in SACC, and miR-138-5p mimic can significantly downregulated the luciferase activity of 293T cells after transfection with a RhoC wild-type plasmid (P<0.05). RhoC is highly expressed in SACC, and RhoC silencing may target the downstream ROCK1/p38MAPK/TWIST1 signaling pathway, thereby inhibiting the proliferation, invasion, migration, and EMT of SACC while promoting its apoptosis. On the contrary, miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC, and there may be binding sites between the two genes.

NLRP3 activation maintains intestinal epithelial barrier and reduces liver injury in alcoholic liver disease mice.

Alcoholic liver disease (ALD) patients with bacterial infections usually exhibit high mortality rates. Infections frequently involve bacteria such as Vibrio vulnificus and Enterococcus faecalis. Nevertheless, the mechanisms predisposing ALD patients to bacterial infections and the role of the NLRP3 inflammasome in the intestinal epithelial barrier in ALD remain unclear. We established ALD mice models of WT, Nlrp3-/- and Gsdmd-/- through chronic alcohol consumption feeding and acute alcohol induction. We compared alterations in gut microbiota, ileitis, and adhesion protein expression, to analyze the role and potential mechanism of NLRP3 in the early onset of ALD. Concurrently, we examined the changes in inflammation and liver damage in the ileum of ALD and healthy mice following foodborne infection with V. vulnificus. Compared with the control group, the expression levels of ZO-1, Claudin-1 and E-cadherin were reduced in the ileum of ALD mice, while those of NLRP3, caspase-1(p20), GSDMD-N and IL-1β were elevated. Nlrp3-/- and Gsdmd-/- ALD mice showed an increased gut bacterial load, decreased ileal expression of E-cadherin, more severe ileitis, pronounced liver damage, steatosis and higher plasma levels of FITC-dextran, D-LA and ZO-1 compared with WT mice. Notably, Nlrp3-/- ALD mice exhibited a higher presence of Deferribacterota and Enterobacteriaceae. Furthermore, ALD mice infected with V. vulnificus infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream infections. This study indicated that NLRP3 activation in the ileum of ALD mice stabilizes the inflammation-related gut microbiota, preserves the intestinal epithelial barrier, and diminishes inflammation and liver injury. Furthermore, the compromised immune defence in ALD mice may contribute to their heightened susceptibility to bacterial pathogens. Activation of the NLRP3-GSDMD pathway in the ileum of Alcoholic liver disease (ALD) mice. NLRP3 activation maintains homeostasis of gut microbiota and intestinal epithelial barrier in ALD mice. ALD mice infected with V. vulnificus infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream infections.

LncRNA H19 improves mesenchymal characteristics of buffalo (Bubalus bubalis) bone marrow-derived mesenchymal stem cells under hypoxic conditions

As adult stem cells with various advantages, Bone marrow-derived mesenchymal stem cells (BMSCs) are valuable resources for veterinary treatment and animal reproduction. Previous studies have shown that hypoxia can induce epithelial-mesenchymal transition (EMT) and improve mesenchymal characteristics of BMSCs in vitro culture. However, the mechanism by which hypoxia improves the interstitial characteristics of buffalo BMSCs (bBMSCs) remains unclear. In this study, the effects of hypoxia on the mesenchymal characteristics of bBMSCs and the expression level of lncRNA H19 were examined, and then the effects of lncRNA H19 on maintaining the mesenchymal characteristics of bBMSCs under hypoxic culture conditions (5% oxygen) as well as its mechanism also were explored, so as to further understand the molecular mechanism of mesenchymal characteristics maintenance of bBMSCs. The results showed that hypoxic culture conditions promoted EMT of bBMSCs, with lncRNA H19 expression up-regulated. When lncRNA H19 was knocked down in hypoxia, the expression level of Vimentin was down-regulated, the expression level of E-Cadherin was up-regulated, and EMT was inhibited. Meanwhile, the genes (p-PI3K and p-AKT1) involved in PI3K/AKT signaling pathway were inhibited by lncRNA H19 Knockdown. IGF-1 (10ng/mL), an activator of PI3K/AKT signaling pathway, was added to rescued the inhibition of PI3K/AKT signaling pathway caused by lncRNA H19 Knockdown, with the effects of lncRNA H19 on EMT related genes also partially reversed. These findings not only provide theoretical guidance to elucidate the detailed regulation mechanism of hypoxia on mesenchymal nature maintenance of bBMSCs, but also provide positive support to further establish the stable in vitro culture system of bBMSCs.

Research on the expression of E-cadherin in lung cancer tumors with different histological structures

Purpose of the study. To conduct a comparative analysis of E-cadherin expression in inoperable patients with non-small cell lung cancer (NSCLC) cells and with different survival rates.Materials and methods. The study included 96 patients with inoperable NSCLC: 84 (87.5 %) men and 12 (12.5 %) women, whose average age was 62.4 ± 0.68 years. Squamous cell carcinoma (SCC) was diagnosed in 78 (81.25 %) patients, and adenocarcinoma (AC) with a tumor differentiation grade of G2-G3 in 18 (18.75 %). The patients were treated and monitored at the National Medical Research Centre for Oncology. The expression of cadherins was determined in the tumor cells of the biopsy specimens. The obtained data have been processed using the Statistica 13.0 program (StatSoftInc., USA). The studied data have been checked for compliance with the normal distribution using the Shapiro-Wilk criterion.Results. The following distribution of patients with NSCLC was noted: IIA – 2 (2.1 %), IIB – 14 (14.6 %), IIIA – 51 (53.1 %), IIIB – 29 (30.2 %), i. e. the frequency of stage III is higher than stage II (83.3 % (n = 80) versus 16.7 % (n = 16), p &lt; 0.001). Fatal outcome occurred in the SCC group within 1 year in 28 patients, within 1 to 2 years – in 30, 20 patients survived for 3 years or more. For AC, these figures were 6,5 and 7 respectively. The analysis revealed that E-cadherin expression was noted in both squamous cell carcinoma and lung adenocarcinoma: Me 55 [LQ 37; UQ 65] and Me 50 [LQ 40; UQ 70], respectively.Conclusions. 1. The analysis revealed that E-cadherin expression was observed in both squamous cell carcinoma and lung adenocarcinomas without statistically significant differences between the compared groups (p = 0.25). 2. Statistically significant differences in the levels of E-cadherin expression were noted in the biopsy samples of the 2 groups only with survival up to 1 year and up to 3 years or more (p &lt; 0.05).

Alanyl-Glutamine Inhibits the Epithelial-Mesenchymal Transition of Airway Epithelial Cells in Asthmatic Mice via DPP4-SIRT1 Pathway

Introduction: Alanyl-glutamine (Ala-Gln) is a compound known for its protective effects in various tissue injuries. However, its role in asthma-related lung injuries remains underexplored. This study investigates the mechanisms by which Ala-Gln modulates sDPP4-induced airway epithelial-mesenchymal transition and ovalbumin (OVA)-induced asthma in a mouse model. Methods: An asthma model was established in female C57BL/6 J mice by using OVA. CD4+ T cells and bronchial epithelial cells (BECs) were isolated from the spleen and bronchi of the mice, respectively. Interventions included recombinant sCD26/sDPP4 protein, Ala-Gln, and EX527 (a SIRT1 inhibitor). Flow cytometry was used to assess Th17 and Treg cell populations. Mice were treated with Ala-Gln, EX527, and budesonide (BUD). Histopathological changes in lung tissues were evaluated using hematoxylin-eosin and Masson staining. White blood cell counts were measured with a hematology analyzer. The expression levels of DPP4, IL-17, SIRT1, SMAD2/3, N-cadherin, E-cadherin, MMP9, and α-SMA proteins were analyzed. Results: Treatment with recombinant sCD26/sDPP4 resulted in decreased E-cadherin expression in BECs and increased levels of α-SMA, MMP9, and N-cadherin, effects that were mitigated by Ala-Gln. Ala-Gln also prevented the reduction in SIRT1 expression in BECs and the increase in Th17 cell differentiation induced by recombinant sCD26/sDPP4. EX527 administration alongside Ala-Gln reversed these changes and enhanced the phosphorylation of SMAD2/3 through SIRT1 signaling. BUD alone reduced inflammation and fibrosis in bronchial tissue and lowered the Th17/Treg ratio in peribronchial lymph nodes. The therapeutic effect of BUD was further improved with concurrent Ala-Gln treatment. Conclusion: Ala-Gln can inhibit BEC fibrosis and Th17 cell differentiation mediated by recombinant sCD26/sDPP4 through the SIRT1 pathway. Combined with BUD, Ala-Gln enhanced therapeutic efficacy in OVA-induced asthma in mice, which could offer improved outcomes for asthmatic patients with elevated DPP4 levels.

Korean Red Ginseng Polysaccharides Enhance Intestinal IgA Production and Barrier Function via Peyer's Patch Activation in Mice.

Background: Natural products are gaining attention for their potential benefits in gastrointestinal health. Plant-derived polysaccharides are essential for boosting intestinal immunity and maintaining gut homeostasis. This study investigated the effects of Korean red ginseng polysaccharides (KRG-P) on intestinal homeostasis including IgA and SCFA production and mucosal barrier integrity. Methods: Mice were orally administered KRG-P at doses of 50 mg/kg or 200 mg/kg for 10 days. Fecal IgA levels were measured on days 3, 5, and 11 and IgA from cultured Peyer's patch cells from KRG-P-treated mice were analyzed. Additionally, mRNA and protein expression levels of α-defensin, lysozyme, and E-cadherin in the small intestine were examined. Short-chain fatty acids (SCFAs) content in the cecum was also assessed. Results: KRG-P-treated groups showed a significant increase in fecal IgA levels on days 5 and 11, with no notable change on day 3. Cultured Peyer's patch cells from mice demonstrated heightened IgA production. Additionally, KRG-P administration upregulated α-defensin and lysozyme mRNA expression, along with elevated protein expression of E-cadherin, α-defensin, and lysozyme, in the small intestine. KRG-P treatment also led to increased cecal SCFA levels, including acetate, butyrate, and propionate. Conclusions: KRG-P may promote intestinal homeostasis and host defense mechanisms by activating immune cells in Peyer's patches, stimulating IgA production, enhancing antimicrobial peptide expression, and modulating gut microbiota metabolism through increased SCFA production.

Effect of phosphorylated HSP27 on the proliferation and metastasis of nasopharyngeal carcinoma and its mechanism

Objective:To investigate the effect of phosphorylated HSP27 on the proliferation and metastasis of nasopharyngeal carcinoma and its molecular mechanism. Methods:①Western blot assay was used to detect the expression levels of HSP27 and p-HSP27 in CNE1 and CNE2 cells of nasopharyngeal carcinoma. Inhibited the phosphorylation of HSP27, Transwell assay detected the metastasis ability of nasopharyngeal carcinoma cells. ②Nasopharyngeal carcinoma cell lines（CNE2-OE1 and CNE2-OE2） overexpressing phosphorylated and dephosphorylated mutants of HSP27 were synthesized, empty vector transfected CNE2 cells（CNE2-NC） were used as controls. The proliferation ability of the three groups of cells was detected by CCK8, and the expression levels of CyclinD1, Bax and Bcl-2 were detected by Western blot. Transwell was used to detect the migration and invasion ability of cells, and Western blot was used to detect the expression levels of E-cadherin, Vimentin, MMP2 and MMP9. Results:The expression level of HSP27 in CNE2 was higher than that of CNE1 cells, while the expression level of p-HSP27 was opposite. After inhibition of HSP27 phosphorylation, the invasion and migration ability of CNE1 cells decreased significantly, with no significant change in CNE2 cells. Compared with CNE2-NC, the growth rate of CNE2-OE1 decreased, and the growth rate of CNE2-OE2 increased. The expression level of CyclinD1 was down-regulated in CNE2-OE1 and higher in CNE2-OE2. The expression level of Bax in CNE2-OE1 was increased, while the expression of Bcl-2 was decreased. There was no significant change in the expression of Bax and Bcl-2 in CNE2-OE2. Compared with CNE2-NC, the migration ability of CNE2-OE1 was enhanced and the invasion ability was weakened, while the migration ability of CNE2-OE2 was weakened and the invasion ability was enhanced. There was no significant difference in the expression levels of E-cadherin was decreased in CNE2-OE1 and increased in CNE2-OE2. There was no significant difference in the expression levels of Vimentin among the three groups. The expression levels of MMP2 and MMP9 were up-regulated in CNE2-OE2, and slightly down-regulated in CNE2-OE1. Conclusion:HSP27 and p-HSP27 were differentially expressed in different nasopharyngeal carcinoma cells, and the metastasis ability of nasopharyngeal carcinoma was not only related to the expression level of HSP27, but also related to the level of p-HSP27. The p-HSP27 inhibited CNE 2 cell proliferation and promoted their apoptosis. As p-HSP27 plays different roles in different stages of nasopharyngeal carcinoma metastasis, it can increase the migration ability of CNE2 cells and reduce its invasion ability. p-HSP27 may induce EMT changes in CNE2 by down-regulating E-cadherin, thus promoting CNE2 migration, and may inhibit CNE2 invasion by down-regulating MMPs expression.

A potential target of GXYLT2 affecting the prognosis of gastric cancer by enhancing the EMT process: A clinical retrospective study.

The present study aimed to investigate glucoside xylosyltransferase 2 (GXYLT2) as a potential prognostic marker for gastric cancer (GC). The expression levels of GXYLT2, Notch1, E-cadherin and vimentin in GC and adjacent tissues were detected by Elivision™️ Plus immunohistochemistry. The relationship between GXYLT2, Notch1, E-cadherin and vimentin, and clinicopathological parameters was also analyzed. Univariate and multivariate Cox regression analyses were conducted to evaluate the effect of GXYLT2 on survival. The results revealed that GC tissues exhibited a marked increase in GXYLT2, Notch1 and vimentin, and a marked reduction in E-cadherin. The expression of GXYLT2 was related to the differentiation degree of GC and the pathological tumor-node-metastasis (pTNM) stage; the expression of Notch1 was related to the vascular and nerve infiltration of GC; and E-cadherin and vimentin expression were related to patient age, tumor size, tumor differentiation degree, depth of infiltration, lymph node metastasis and pTNM stage. Positive associations existed between GXYLT2 and Notch1 expression, GXYLT2 and vimentin expression, and Notch1 and vimentin expression. Furthermore, the Kaplan-Meier analysis showed that survival and prognosis were associated with factors such as GXYLT2 protein levels, pTNM stage, tumor dimensions, depth of infiltration and lymph node metastasis. Through Cox regression analysis, GXYLT2 was identified as an independent predictor for GC. In conclusion, GXYLT2 may be related to the pathogenesis of GC, and its abnormal expression could be associated with epithelial-mesenchymal transition. Consequently, GXYLT2 may be considered a promising prognostic marker in the context of GC.

Scutellarein ameliorates dextran sulfate sodium-induced ulcerative colitis by inhibiting colonic epithelial cell proinflammation and barrier disruption.

Scutellarein (Scu) is a natural occurring flavonoid found in multiple traditional Chinese medicines such as Oroxylum indicum (L.) Kurz and Scutellaria baicalensis, with various pharmacological activities including anti-inflammation, anti-oxidation and myocardial protection. Here, we investigated the therapeutic efficacy of Scu on ulcerative colitis (UC) and the underlying mechanism. Efficacy of Scu on UC was evaluated in dextran sulfate sodium (DSS) induced colitis mouse model. Inflammation in colonic tissues was assessed by myeloperoxidase activity assay and RT-qPCR. Barrier proteins expression was examined using immunostaining and Western blot. IL-1β-treated HT-29 cells was used for mechanical investigation. Gavage of Scu significantly decreased the DAI score, improved colon shortening, ameliorated the pathological score in DSS-treated mice with better efficacy than the positive drug, 5-aminosalicylic acid. Scu also inhibited the expression levels of cytokines (Il-1β, Tnf-α, Il-1α, Il-6, and Cxcl1) as well as barrier proteins (E-cadherin, Occludin, and ZO-1) in colon tissues of DSS mice. In intestinal epithelial HT-29 cells, Scu attenuated the IL-1β-downregulated expression levels of E-cadherin, occludin, and ZO-1, while reduced IL-1β-upregulated IL-6 and IL-8 mRNA levels. Moreover, Scu inhibited the phosphorylation and nuclear translocation of NF-κB and suppression of NF-κB phosphorylation abolished IL-1β-disrupted epithelial barrier integrity and IL-1β-upregulated proinflammatory mediators expression in HT-29 cells. These data demonstrate that Scu is an efficacious therapeutic agent to treat UC. Inhibition of inflammatory responses and maintenance of epithelial barrier integrity through NF-κB signaling pathway underlines Scu therapeutic effect on UC.

Euphorbia helioscopia inhibits proliferation, invasion, and migration and promotes apoptosis of non-small cell lung cancer cells

To investigate the effect of Euphorbia helioscopia on biological behaviors of non-small cell lung cancer (NSCLC) cells. NSCLC cell lines PC-9 and A549 treated with different concentrations of Euphorbia helioscopia preparations were examined for changes in proliferation, apoptosis, invasion and migration using CCK-8 assay, colony formation assay, flow cytometry, wound healing assay and Transwell assay. Western blotting was performed to detect the changes in protein expressions of Bax, Bcl-2, E-cadherin, vimentin, MMP2, and MMP9 in the treated cells. PC-9 cells were injected subcutaneously into BALB/C nude mice to establish a nude mouse subcutaneous tumor model. According to the growth of subcutaneous tumors, mice were randomly divided into control group: gavaged daily with saline; Euphorbia helioscopia-treated group: gavaged daily with Euphorbia helioscopia 65 mg/mL, and Euphorbia helioscopia granules were dissolved in saline; cisplatin-treated group: injected intraperitoneally with cisplatin 4 mg/kg every 5 days, 6 mice per group. The subcutaneous tumor volume and mass changes of mice were measured, and the toxic effects of Euphorbia helioscopia on heart, liver, spleen, lung and kidney as well as the therapeutic effects of Euphorbia helioscopia were observed in the mice bearing tumor. Euphorbia helioscopia granules concentration-dependently inhibited the proliferation and survival of PC-9 and A549 cells, significantly promoted cell apoptosis, suppressed invasion and migration abilities of the cells, up-regulated the expression levels of E-cadherin and Bax, and down-regulated the expressions of Bcl-2, vimentin, MMP2, and MMP9. In the tumor-bearing mice, treatment with Euphorbia helioscopia significantly inhibited tumor growth without producing obvious toxicity in the vital organs. Euphorbia helioscopia can inhibit proliferation, invasion, and migration and induces apoptosis of NSCLC cells in vitro.

The effects of fumonisin B1 on intercellular communications and miRNA modulations: Non-genotoxic carcinogenesis mechanisms in human kidney cells

Fumonisin B1 (FB1), which is produced by Fusarium species, is one of the most prevalent mycotoxins known to exert several toxic effects, particularly nephrotoxicity. While its genotoxic carcinogenic mechanisms have been extensively studied, its influence on non-genotoxic pathways including intercellular communication and microRNA (miRNA) regulation remain underexplored. The present study investigates the effects of FB1 on gap junctions, miRNA expression profiles, and their relationship in human kidney cells (HK-2 and HEK293). Both cell lines showed increased apoptosis rates at 50 and 100 µM, while FB1 exposure significantly reduced gap junctional intercellular communication (GJIC) and decreased the expression levels of related genes, including Cx43, Cx45, e-cadherin, Cadherin-2, and β-catenin. After FB1 treatments alteration on the regulation of miRNAs including let-7a-5p, miR-125a-5p, miR-222-3p, miR-92a-3p, let-7b-5p, let-7e-5p, miR-21-5p, miR-155-5p, let-7i-5p, let-7d-5p, let-7f-5p, miR-181b-5p, miR-15b-5p, miR-23b-3p, miR-20b-5p, miR-196a-5p miRNAs have been shown. Let-7a-5p was selected among the altered miRNAs to elucidate the relationship between miRNAs and GJIC after FB1 exposure as it is one of the common miRNAs that changes in both cell lines and one of its target genes is Cx45, which is an important gene for GJIC. However, transfection analysis did not show any differences, resulting in Cx45 not being a direct target of let-7a-5p in HK-2 and HEK-293 cells. Through comprehensive analysis, we elucidated that FB1's impact on intercellular signaling cascades and its regulatory role on miRNA expression profiles, offering valuable insights into carcinogenesis beyond traditional genotoxic paradigms. Understanding these mechanisms is crucial for elucidating the mechanisms of FB1-induced toxicity.

Chrysene contribution to bronchial asthma: Activation of TRPA1 disrupts bronchial epithelial barrier via ERK pathway

Elevated polycyclic aromatic hydrocarbon (PAH) levels are associated with exacerbation of asthma. Chrysene is one of the most prevalent unsubstituted PAHs in the environment. Transient receptor potential ankyrin 1 (TRPA1) can be used as a chemoreceptor to detect inhaled stimuli and plays an important role in the occurrence and deterioration of asthma. Whether exposure to a high concentration of chrysene in the environment can activate TRPA1 and contribute to the development of asthma, potentially through the dysfunction of the bronchial epithelial barrier, remains unclear. A cell-based assay was performed to verify the downregulation of the expression of E-cadherin and tight junction (TJ) proteins by chrysene in bronchial epithelial cells to explore the role of chrysene-mediated TRPA1 activation in the regulation of TJ protein expression through the extracellular signal-regulated protein kinase (ERK) pathway. Animal tests were conducted to determine whether chrysene could enhance airway hyperresponsiveness (AHR) induced by house dust mites (HDMs) and disrupt barrier function, thereby contributing to asthma. The cell-based assay revealed that chrysene could disrupt the function of the bronchial epithelial barrier and decrease the expression levels of E-cadherin, zonula occludens-1 (ZO-1), occludin, and claudin-5 through the ERK pathway. Chrysene induced airway epithelial barrier dysfunction primarily through TRPA1 instead of transient receptor potential vanilloid 1. TRPA1 knockdown was able to attenuate chrysene-induced downregulation of TJ protein expression and downregulate ERK activation (p-ERK). Compared with exposure to HDM alone, coexposure to chrysene and HDM resulted in an increased incidence of AHR, disruption of barrier function, and eosinophilic inflammatory responses in a mouse model of asthma. Coexposure to chrysene and HDM increased TRPA1 expression. The animal test verified that the TRPA1 inhibitor HC030031 could suppress chrysene and HDM-induced asthma in mice. Our findings showed that chrysene contributed to the breakdown of the function of the bronchial epithelial barrier through the TRPA1-ERK axis and therefore acted as an adjuvant to contribute to asthma.