Dioscin ameliorates inflammatory bowel disease by up-regulating miR-125a-5p to regulate macrophage polarization.

PURPOSE: Dioscin has been proven to have anti-cancer, anti-inflammatory, and anti-infection roles. However, the role of Dioscin in inflammatory bowel disease (IBD) and its related mechanisms is unclear and needs further study. METHODS: The colitis model in mice was established. After Dioscin (20, 40, or 80 mg/kg) treatment, the colon length was measured by a ruler. Histopathology, inflammatory cytokines, gut permeability, tight junction proteins, macrophage infiltration, macrophage polarization, and miR-125a-5p level were detected by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), FITC-dextran, Western blot, and flow cytometry. In vitro experiments, after RAW264.7 cells induced by lipopolysaccharide (LPS)/interleukin-4 (IL-4), were treated with Dioscin and miR-125a-5p inhibitor, miR-125a-5p level, cell vitality, inflammatory cytokines, and M1/M2 marker genes were measured by qRT-PCR and MTT assay. RESULTS: Dioscin (20, 40, or 80 mg/kg) relieved DSS-triggered colitis and restrained the serum and colon of pro-inflammatory cytokines expression. Meanwhile, different concentrations' Dioscin weakened M1 macrophage polarization but facilitated tight junction protein expressions, M2 macrophage polarization, and miR-125a-5p level in colitic mice. Moreover, miR-125a-5p inhibitor reversed the modulation of Dioscin on miR-125a-5p expression, cell vitality, and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW264.7 cells. We further discovered that Dioscin restrained M1 marker gene (CD16) expression while intensifying M2 marker genes (CD206 and Arginase-1) expressions in vitro, which was reversed by miR-125a-5p inhibitor. CONCLUSION: Dioscin modulated macrophage polarization by increasing miR-125a-5p, thereby improving the intestinal epithelial barrier function and reducing IBD.

Crystallographic snapshots of the interplay between reactive guest and host molecules in a porous coordination polymer: stereochemical coupling and feedback mechanism of three photoactive centers triggered by UV-induced isomerization, dimerization, and polymerization reactions.

We carried out photopolymerization by [2 + 2] dimerization of a photoreactive guest molecule in the channels of a photoreactive porous coordination polymer. The photoreactions of the guest and two host ligands were monitored by single-crystal X-ray crystallography, providing snapshots of the interplay between the reactive centers. By correlating the structures of these three photocenters, a strong synergism was discovered among three reaction (quasi)equilibria and three types of photochemical reactions (isomerization, dimerization, and polymerization). This result indicates a strong coupling and feedback mechanism among the photocenters moderated by the coordination backbone.

The variation of expression of CD4+ CD25+ Foxp3+ regulatory T cells in patients with Helicobacter pylori infection and eradication.

BACKGROUND/AIMS: H. pylori persists for the virtual life of its host. Recent studies suggested that CD4 CD25+ regulatory T cells may be involved in this process. However, the alteration of CD4+ CD25+ regulatory T cells after eradication of H. pylori remains a question. METHODOLOGY: By using biopsies from 45 H. pylori-positive patients and the ones after eradication of H. pylori and 35 H. pylori-negative adults, real-time PCR and general PCR were used to quantify the expression of Foxp3 mRNA. IHC was used to semi- quantify the number of CD4+ CD25+ T cells in gastric mucosa. RESULTS: We found that proportion ofCD25+ T cell in CD4+ T cells accounted for 0.739% in H. pylori-negative individuals, while it was accounted for 5.012% in H. pylori-positive patients. After eradication of H. pylori, proportion of CD25+ T cell in CD4+ T cells declined (P mRNA significantly decreased (P < 0.01) in gastric mucosa of patients after eradication of H. pylori. CONCLUSIONS: CD4+ CD25+ regulatory T cells decreased in gastric mucosa when patients received eradication of H. pylori. Eradication of H. pylori results in the significant decrease of Foxp3 mRNA in gastric mucosal, or using the drugs of anti-H. pylori induce the reduction of gastric mucosal Foxp3 mRNA expression, which is the a key regulatory gene for the development and function of CD4+ CD25+ regulatory T cells, thus contributing to the eradication of H. pylori. All the data offer new possibilities that Foxp3 gene may be the new target of immunization intervention strategies for eradication of H. pylori.

Associations between the compositional patterns of blood volatile organic compounds and chronic respiratory diseases and ages at onset in NHANES 2003-2012.

BACKGROUND: and Purpose Volatile organic compounds (VOCs) pose a serious respiratory hazard. This study evaluated the relationship between the compositional patterns of blood VOCs and the risk and age at onset of chronic respiratory diseases (CRDs), including asthma, emphysema and chronic bronchitis, with the objective of preventing or delaying CRDs. METHODS: Participants from five cycles of the NHANES survey were included. Blood VOCs were clustered using k-means clustering. Differences in VOCs and age at onset between multiple groups were compared with the Kruskal‒Wallis test. Logistic regression and a generalized linear model were applied to examine the associations between different compositional patterns of blood VOCs and risk and age at onset of CRDs. RESULTS: 12,386 participants were enrolled in this study. Three VOC compositional patterns were identified after clustering nine species of blood VOCs. The concentration of VOCs in pattern 2 was relatively low and stable. The concentrations of benzene, ethylbenzene, o-xylene, styrene, toluene and m-p-xylene in pattern 3 and the concentrations of 1,4-dichlorobenzene and MTBE in pattern 1 were significantly higher than those in pattern 2. After adjustment for covariates, the participants with VOC pattern 3 had an increased risk of asthma (OR = 1.23, 95% CI: 1.02, 1.49), emphysema (OR = 3.37, 95% CI: 2.24, 5.06) and chronic bronchitis (OR = 1.79, 95% CI: 1.30, 2.45). Meanwhile, VOC pattern 3 was negatively correlated with the age at onset of asthma (ß = -5.61, 95% CI: 9.69, -1.52) and chronic bronchitis (ß = -9.17, 95% CI: 13.96, -4.39). VOC pattern 1 was not associated with either risk or age at onset of the three CRDs after adjustment. CONCLUSIONS: Changing the compositional pattern of blood VOCs by reducing certain species of VOCs may be a new strategy to lengthen the ages at onset of CRDs and effectively prevent them.

Endoscopic ultrasonography in the evaluation of condition and prognosis of ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is usually diagnosed through histopathology, enteroscopy, clinical symptoms, and physical findings; however, it is difficult to accurately evaluate disease severity. AIM: To investigate the value of endoscopic ultrasonography (EUS) in the evaluation of the severity and prognosis of UC. METHODS: Patients with UC who were seen in our hospital from March 2019 to December 2020 were eligible, and disease severity was evaluated according to the modified Truelove and Witts and Mayo scores. We performed EUS, calculated the UC endoscopic index of severity (UCEIS) and EUS-UC scores, and administered appropriate treatment. The UCEIS and EUS-UC scores of patients were assessed in relation to disease severity, and the correlations between UCEIS and EUS-UC scores and disease severity was also analyzed. The UCEIS and EUS-UC scores before and after treatment were also compared. RESULTS: A total of 79 patients were included in this study. According to the Mayo Index, 23, 32, and 24 patients had mild, moderate and severe UC, respectively. The UCEIS and EUS-UC scores were higher in moderate cases (4.98 ± 1.04 and 5.01 ± 0.99, respectively) than in mild cases (1.56 ± 0.82 and 1.64 ± 0.91, respectively, P < 0.05). Furthermore, the UCEIS and EUS-UC scores (7.31 ± 1.10 and 7.59 ± 1.02, respectively) were higher in severe cases than in moderate cases (P < 0.05). According to the modified Truelove and Witts scores, 21, 36, and 22 patients were classified as having mild, moderate and severe disease, respectively. The UCEIS and EUS-UC scores were significantly higher in moderate disease (4.79 ± 1.11 and 4.96 ± 1.23, respectively) than in mild disease (1.71 ± 0.78 and 1.69 ± 0.88, respectively, P < 0.05). Additionally, the UCEIS and EUS-UC scores in severe disease (7.68 ± 1.22 and 7.81 ± 0.90, respectively) were significantly higher than in moderate disease (P < 0.05). The UCEIS and EUS-UC scores were significantly and positively correlated with disease severity according to the modified Truelove and Witts score and Mayo score (P < 0.05). The UCEIS and EUS-UC scores after 2 mo of treatment (3.88 ± 0.95 and 4.01 ± 1.14, respectively) and after 6 mo of treatment (1.59 ± 0.63 and 1.64 ± 0.59, respectively) were lower than the respective scores before treatment (5.93 ± 1.79 and 6.04 ± 2.01) (P < 0.05). CONCLUSION: EUS can clarify the status of UC and accurately evaluate the treatment response, providing an objective basis for formulation and adjustment of the treatment plan.

The variation of expression of CD4+ CD25+ Foxp3+ regulatory T cells in patients with Helicobacter pylori infection and eradication.

BACKGROUND/AIMS: H. pylori persists for the virtual life of its host. Recent studies suggested that CD4+ CD25+ regulatory T cells may be involved in this process. However, the alteration of CD4+ CD25+ regulatory T cells after eradication of H. pylori remains a question. METHODOLOGY: By using biopsies from 45 H. pylori-positive patients and the ones after eradication of H. pylori and 35 H. pylori-negative adults, real-time PCR and general PCR were used to quantify the expression of Foxp3 mRNA. IHC was used to semi-quantify the number of CD4+ CD25+ T cells in gastric mucosa. RESULTS: We found that proportion of CD25+ T cell in CD4+ T cells accounted for 0.739% in H. pylori-negative individuals, while it was accounted for 5.012% in H. pylori-positive patients. After eradication of H. pylori, proportion of CD25+ T cell in CD4+ T cells declined (p < 0.01) and it accounted for 0.551%. The level of Foxp3 mRNA significantly decreased (p < 0.01) in gastric mucosa of patients after eradication of H. pylori. CONCLUSIONS: CD4+ CD25+ regulatory T cells decreased in gastric mucosa when patients received eradication of H. pylori. Eradication of H. pylori results in the significant descrease of Foxp3 mRNA in gastric mucosal, or using the drugs of anti-H. pylori induce the reduction of gastric mucosal Foxp3 mRNA expression, which is the a key regulatory gene for the development and function of CD4+ CD25+ regulatory T cells, thus contributing to the eradication of H. pylori. All the data offer new possibilities that Foxp3 gene may be the new target of immunization intervention strategies for eradication of H. pylori.

10H-Phenothia-zine 5-oxide.

In the title compound, C(12)H(9)NOS, the sulfoxide O atom is disordered over two sites with occupancies of 0.907 (4) and 0.093 (4). The dihedral angle betweeen the two aromatic rings is 18.40 (14)°. Different types of supramolecular interactions including inter-molecular N-H⋯O hydrogen bonds and π-π contacts [centroid-centroid distances = 3.9096 (16) and 4.1423 (16) Å] between the aromatic rings of symmetry-related mol-ecules are observed in the crystal structure.

The role of CXCL chemokine family in the development and progression of gastric cancer.

The chemokine (C-X-C motif) ligand (CXCL) family plays an important role in inflammation. In order to understand the role of CXC chemokine family in carcinogenesis, this study explored a group of early gastric cancer (GC) patients, and assessed the level of CXC chemokine ligand (CXCL) in blood samples of patients representing systemic circulation and tumor microenvironment, detected the expression of CXC chemokine receptor (CXCR) in tumor tissues, and measured tumor infiltrating immune cell subsets. 69 patients with GC were included in a single center prospective study and were followed up for 6 years. The level of CXCL1-14 was determined by ELISA and the concentration gradient of chemokine was calculated. Western blot was used to detect the expression of CXCR1, CXCR2, CXCR3, and CXCR4 in tumor tissue. CXCL1-14 expression was inhibited by siRNA in HGC27 cells and then the migration ability of HGC27 cells was detected by cell scratch test. The results of this study showed that the chemokine concentrations of CXCL1, CXCL2, CXCL5, CXCL8, CXCL11, and CXCL13 in peripheral blood and tumor drainage blood of patients without recurrence after treatment were significantly lower than those before treatment. The concentrations of CXCL1, CXCL2, CXCL4, CXCL5, CXCL7, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13, and CXCL14 in peripheral blood and tumor drainage blood were significantly higher than those in patients without recurrence. Patients with low expression of CXCR1 and CXCR3 had lower AFP (alpha fetoprotein), smaller tumor volume, and lower TNM tumor stage. Patients with lower expression of CXCR2 and CXCR4 had higher AFP (alpha fetoprotein) level, larger tumor volume, and higher TNM tumor stage. After down-regulation of CXCLs expression, the migration ability of most cell lines was significantly inhibited. This study suggests that CXCL chemokine family plays an important role in the pathogenesis of GC and can be used as a marker for the development of GC.

Complementary action of CXCL1 and CXCL8 in pathogenesis of gastric carcinoma.

Chemokine (C-X-C motif) ligand (CXCL) is a class of secreted growth factor that signals through a G-protein coupled receptor. CXCL protein family members play important roles in inflammation and aberrant expression is associated with growth and progression of certain tumors. To explore the expression pattern and action mechanism of CXCL1 and CXCL8 in development of gastric carcinoma (GC), 72 cases of GC and para-carcinoma tissue specimens were used for experimental study, and qPCR was used for analysis on the expression of CXCL1 and CXCL8 in GC specimens. For in vitro culture of GC cell HGC27, knockout of CXCL1 and CXCL8 genes for GC cell HGC27 was performed through RNA interference, proliferation of HGC27 cells was tested by MTT, apoptosis of HGC27 cells was tested by flow cytometry, and the influence of CXCL1 and CXCL8 on HGC27 cell migration was tested by transwell. CXCL1 and CXCL8 expression level in HGC27 cells was analyzed by Western blotting. Co-immunoprecipitation (co-IP) was used for identifying interaction of CXCL1 and CXCL8 with CXCR2 in GC cells. The results show that both CXCL1 and CXCL8 expression were significantly up-regulated. Relevant clinical data showed that low expression of CXCL1 and CXCL8 significantly correlated with features for poor prognosis of GC, including serum alpha-fetoprotein (AFP) level, tumor size, and TNM staging. Down-regulation of CXCL1 and CXCL8 may up-regulate expression of each other and thus silencing expression of CXCL1 and CXCL8 may significantly inhibit proliferation and migration capabilities of HGC27 cells, and induce the apoptosis. Downregulated CXCL1 and CXCL8 expression in GC cells may significantly intensify interaction of one another and with CXCR2. The above results indicate that CXCL1 and CXCL8 participate in GC proliferation, apoptosis, and migration processes through specific binding with CXCR2 by a synergistic effect.

REG3A promotes the proliferation, migration, and invasion of gastric cancer cells.

The mechanism underlying the metastasis of gastric cancer (GC) cells remains elusive. REG3A is considered an oncogene in various cancers, but in GC its role is unclear. Here, we report that the expression of REG3A was significantly increased in the tumor tissues of patients with GC compared with the matched normal tissues. Knockdown of REG3A induced by specific small interfering RNA (siRNA) significantly repressed the proliferation of GC cells for 24 h or 48 h. Moreover, knockdown of REG3A significantly suppressed the migration, invasion, and adhesion of GC cells in vitro. Furthermore, knockdown of REG3A reduced the phosphorylation of JAK2 and STAT3, and altered the messenger RNA (mRNA) and protein expression levels of E-cadherin, Snail, RhoC, MTA1, MMP-2, and MMP-9. Taken together, REG3A is overexpressed in GC and promotes the proliferation, migration, invasion, and adhesion of GC cells by regulating the JAK2/STAT3 signal pathway. REG3A may be a potential therapeutic target for GC.