Upregulated Tß4 expression in inflammatory bowel disease impairs the intestinal mucus barrier by inhibiting autophagy in mice.

Disrupted intestinal barrier homeostasis is fundamental to inflammatory bowel disease. Thymosin ß4 (Tß4) improves inflammation and has beneficial effects in dry-eye diseases, but its effects on the intestinal mucus barrier remain unknown. Therefore, this study evaluated the underlying regulatory mechanisms and effects of Tß4 by examining Tß4 expression in a mouse model with dextran sodium sulfate (DSS)-induced colitis and colonic barrier damage. Additionally, we intraperitoneally injected C57BL/6 mice with Tß4 to assess barrier function, microtubule-associated protein 1 light chain 3 (LC3II) protein expression, and autophagy. Finally, normal human colon tissue and colon carcinoma cells (Caco2) were cultured to verify Tß4-induced barrier function and autophagy changes. Mucin2 levels decreased, microbial infiltration increased, and Tß4 expression increased in the colitis mouse model versus the control mice, indicating mucus barrier damage. Moreover, Tß4-treated C57BL/6 mice had damaged intestinal mucus barriers and decreased LC3II levels. Tß4 also inhibited colonic mucin2 production, disrupted tight junctions, and downregulated autophagy; these results were confirmed in Caco2 cells and normal human colon tissue. In summary, Tß4 may be implicated in colitis by compromising the integrity of the intestinal mucus barrier and inhibiting autophagy. Thus, Tß4 could be a new diagnostic marker for intestinal barrier defects.

Amplitude-phase modulated composite waves in coupled nonlocal system with self-induced PT symmetric potential.

We consider a coupled nonlocal nonlinear Schrödinger equation (nNLSE) with self-induced parity-time (PT) symmetric potential and investigate abundant amplitude-phase modulated composite waves manifesting diverse evolution patterns. It is found that the coupled nonlocal model can be decoupled into nNLSEs with self-induced PT symmetric potential under certain constraints through a general linear transformation with amplitude and phase modulation. Based on the exact solutions of the nNLSEs with self-induced PT potential, we study various composite waves superposed by bright and/or dark soliton solutions, rogue waves, bright/dark soliton and periodic soliton, and present the abundant evolution patterns under amplitude-phase modulation. The results here only demonstrate the characteristics of limited superposed composite waves. In fact, there exist infinite possible evolution patterns of composite waves due to the arbitrary amplitude-phase modulation in coupled nonlocal nonlinear system with self-induced PT symmetric potential.

A Novel Mast Cell Stabilizer JM25-1 Rehabilitates Impaired Gut Barrier by Targeting the Corticotropin-Releasing Hormone Receptors.

Mast cell (MC) plays a central role in intestinal permeability; however, few MC-targeting drugs are currently available for protection of the intestinal barrier in clinical practice. A nonfluorinated Lidocaine analog 2-diethylamino-N-2,5-dimethylphenyl acetamide (JM25-1) displays anti-allergic effect, but its impact on MC remains elusive. In this study, we explored whether JM25-1 has therapeutic potential on intestinal barrier defect through stabilizing MC. JM25-1 alleviated release of ß-hexosaminidase and cytokine production of MC. The paracellular permeability was redressed by JM25-1 in intestinal epithelial cell monolayers co-cultured with activated MC. In vivo, JM25-1 diminished intestinal mucosal MC amount and cytokine production, especially downregulating the expression of CRHR1, accompanied by an increase of CRHR2. Protective effects appeared in JM25-1-treated stress rats with a recovery of weight and intestinal barrier integrity. Through network pharmacology analysis, JM25-1 showed a therapeutic possibility for irritable bowel syndrome (IBS) with predictive targeting on PI3K/AKT/mTOR signaling. As expected, JM25-1 reinforced p-PI3K, p-AKT, p-mTOR signaling in MC, while the mTOR inhibitor Rapamycin reversed the action of JM25-1 on the expression of CRHR1 and CRHR2. Moreover, JM25-1 successfully remedied intestinal defect and declined MC and CRHR1 expression in rat colon caused by colonic mucus of IBS patients. Our data implied that JM25-1 possessed therapeutic capacity against intestinal barrier defects by targeting the CRH receptors of MC through PI3K/AKT/mTOR signaling.

[Expression of laminin and laminin receptor in gestational trophoblastic tumor and its significance].

OBJECTIVE: This study was conducted to detect the expression of laminin (LN) and laminin receptor (LN-R) in the specimens of hydatidiform mole (HM), invasive mole (IM) and choriocarcinoma(CC), respectively. METHODS: The immunohistological staining method was used. RESULTS: It was found that the level of the laminin expression was higher in the specimens of choriocarcinoma at more advanced stage. CONCLUSION: The results suggest that there may be relations between the invasion and metastasis of choriocacinoma cell and the malignant degree of this disease, chemotherapy has some effect on the expression of LN and LN-R in gestational trophablastic tumor (GTT), and that LN and LN-R may be of potential value in GTT treatment. However, referring whether LN and LN-R could be used as clinical prognosticators, further studies will be needed.