IL-17A Promotes Initiation and Development of Intestinal Fibrosis Through EMT.

BACKGROUND: Intestinal fibrosis is a common complication of Crohn's disease (CD). Its exact mechanism is still unclear, and effective treatments to control or reverse the fibrosis process are unavailable. Epithelial-mesenchymal transition (EMT) may promote intestinal fibrosis by increasing deposition of extracellular matrix protein. IL-17A is a pro-inflammatory cytokine, and it has been shown as a profibrotic factor as its association with fibrosis of multiple organs was reported. AIMS: To assess the roles of IL-17A and EMT in the initiation and development of intestinal fibrosis and to verify the potential inductive effect of IL-17A on EMT. METHODS: In this study, we evaluated the expression of IL-17A and EMT-related genes in colonic mucosal biopsy tissues of CD patients and control individuals. Then, we examined the changes of EMT-related genes and fibrosis-related genes of IEC-6 cells which cultured for 72 h under increasing concentrations of IL-17A or with TGF-ß1, to verify the potential inductive effect of IL-17A on EMT in vitro. We blocked the IL-17A of the mouse model of TNBS-induced experimental intestinal colitis and fibrosis to further verify the potential inductive effect of IL-17A on EMT in vivo. RESULTS: We found the occurrence of EMT and high-level expression of IL-17A in intestinal mucosa of CD patients. Using IEC-6 cells, we showed that IL-17A may induce EMT in intestinal epithelial cells that come with reduced E-cadherin expression and increased expression of vimentin, snail, and α-SMA. We further found that anti-IL-17A treatment alleviated intestinal fibrosis through reducing EMT in mouse intestine. CONCLUSIONS: Our study confirmed the involvement of IL-17A in the development of intestinal fibrosis through inducing EMT.

Mucosal esophageal carcinoma following endoscopic submucosal dissection with giant gastric metastasis: A case report and review of literature.

BACKGROUND: Esophageal carcinoma is a highly aggressive digestive cancer responsible for a notable proportion of cancer-related deaths worldwide. Its elevated metastatic rate contributes to a poor prognosis in affected patients. In this case review, we aim to summarize the metastatic characteristics of intramural gastric metastasis (IGM) in mucosal esophageal squamous carcinoma. CASE SUMMARY: A 56-year-old man was admitted to our hospital because of a dry cough with an esophageal sensation for one year. Endoscopic examination revealed a 2.0 cm 1.0 cm, superficial esophageal squamous cell carcinoma, and the patient underwent endoscopic submucosal dissection (ESD). Fifteen months after ESD, positron emission tomography/computed tomography revealed that the metabolism of the stomach cardia wall had increased slightly. However, the mucosa of the gastric cardia was smooth under gastroendoscopy. Two years after ESD, endoscopic examination revealed a giant gastric cardia carcinoma, while the esophageal mucosa was smooth, and no advanced cancer was found. A biopsy of the gastric cardia indicated squamous-cell carcinoma. The patient received immunochemotherapy and radiotherapy for esophageal cancer for 8 mo and is currently under follow-up. CONCLUSION: Early-stage esophageal carcinoma with IGM is rare. Despite the ESD of the primary lesion, IGM may still occur and should be closely monitored after ESD.

Endoscopic and pathological characteristics of de novo colorectal cancer: Retrospective cohort study.

BACKGROUND: Endoscopy has rapidly developed in recent years and has enabled further investigation into the origin and features of intestinal tumors. The small size and concealed position of these tumors make it difficult to distinguish them from nonneoplastic polyps and carcinoma in adenoma (CIA). The invasive depth and metastatic potential determine the operation regimen, which in turn affects the overall survival and distant prognosis. The previous studies have confirmed the malignant features and clinicopathological features of de novo colorectal cancer (CRC). AIM: To provide assistance for diagnosis and treatment, but the lack of a summary of endoscopic features and assessment of risk factors that differ from the CIA prompted us to conduct this retrospective study. METHODS: In total, 167 patients with small-sized CRCs diagnosed by endoscopy were reviewed. The patients diagnosed as advanced CRCs and other malignant cancers or chronic diseases that could affect distant outcomes were excluded. After screening, 63 cases were excluded, including 33 de novo and 30 CIA cases. Patient information, including their follow-up information, was obtained from an electronic His-system. The characteristics between two group and risk factors for invasion depth were analyzed with SPSS 25.0 software. RESULTS: Nearly half of the de novo CRCs were smaller than 1 cm (n = 16, 48.5%) and the majority were located in the distal colon (n = 26, 78.8%). The IIc type was the most common macroscopic type of de novo CRC. In a Pearson analysis, the differential degree, Sano, JNET, and Kudo types, surrounding mucosa, and chicken skin mucosa (CSM) were correlated with the invasion depth (P < 0.001). CSM was a significant risk factor for deep invasion and disturbed judgment of endoscopic ultrasound. A high degree of tumor budding and tumor-infiltrating lymphocytes are accompanied by malignancy. Finally, de novo CRCs have worse outcomes than CIA CRCs. CONCLUSION: This is the first comprehensive study to analyze the features of de novo CRCs to distinguish them from nonneoplastic polyps. It is also the first study paying attention to CSM invasive depth measurement. This study emphasizes the high metastatic potential of de novo CRCs and highlights the need for more research on this tumor type.

Mechanism of ELL-associated factor 2 and vasohibin 1 regulating invasion, migration, and angiogenesis in colorectal cancer.

BACKGROUND: As a novel endogenous anti-angiogenic molecule, vasohibin 1 (VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colorectal cancer (CRC). Knockdown of VASH1 enhanced transforming growth factor-ß1 (TGF-ß1)/Smad3 pathway activity and type I/III collagen production. Our previous findings suggest that ELL-associated factor 2 (EAF2) may play a tumor suppressor and protective role in the development and progression of CRC by regulating signal transducer and activator of transcription 3 (STAT3)/TGF-ß1 signaling pathway. However, the functional role and mechanism of VASH1-mediated TGF-ß1 related pathway in CRC has not been elucidated. AIM: To investigate the expression of VASH1 in CRC and its correlation with the expression of EAF2. Furthermore, we studied the functional role and mechanism of VASH1 involved in the regulation and protection of EAF2 in CRC cells in vitro. METHODS: We collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein and VASH1 protein in patients with advanced CRC. Following, we investigated the effect and mechanism of EAF2 and VASH1 on the invasion, migration and angiogenesis of CRC cells in vitro using plasmid transfection. RESULTS: Our findings indicated that EAF2 was down-regulated and VASH1 was up-regulated in advanced CRC tissue compared to normal colorectal tissue. Kaplan-Meier survival analysis showed that the higher EAF2 Level group and the lower VASH1 Level group had a higher survival rate. Overexpression of EAF2 might inhibit the activity of STAT3/TGF-ß1 pathway by up-regulating the expression of VASH1, and then weaken the invasion, migration and angiogenesis of CRC cells. CONCLUSION: This study suggests that EAF2 and VASH1 may serve as new diagnostic and prognostic markers for CRC, and provide a clinical basis for exploring new biomarkers for CRC. This study complements the mechanism of EAF2 in CRC cells, enriches the role and mechanism of CRC cell-derived VASH1, and provides a new possible subtype of CRC as a therapeutic target of STAT3/TGF-ß1 pathway.

Effectiveness of resilience-promoting interventions in adolescents with diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: This study aimed to analyze the efficacy of resilience-promoting interventions among adolescents and youth aged 10-24 years with any type of diabetes. METHODS: A systematic literature search was performed using the PubMed, Web of Science, Embase, Cochrane Library, CINAHL, and PsycINFO databases from inception to May 25, 2022. The Cochrane risk of bias tool (version 2) was used to assess the quality of the included studies. A meta-analysis was performed to calculate the pooled effects of resilience-promoting interventions. RESULTS: Nineteen articles were included covering an overall sample of 2048 adolescents with diabetes. When analyzing the effectiveness of resilience-promoting interventions, hemoglobin A1c (HbA1c) at six months [mean difference = - 0.47, 95% confidence interval (CI) = - 0.83 to - 0.12, P = 0.009] after the intervention was improved. However, long-term (≥ 12 months) improvement in HbA1c was not significant. In addition, comparing the control group, there were significant differences in the effect size for stress [standardized mean difference (SMD) = - 0.87, 95% CI = - 1.25 to -0.48, P < 0.05], self-efficacy (SMD = 0.50, 95% CI = 0.02-0.98, P = 0.04) and quality of life (SMD = 0.27, 95% CI = 0.03-0.51, P = 0.03). CONCLUSIONS: Resilience-promoting intervention is a promising way for adolescent diabetes management to improve HbA1c, stress, self-efficacy, and quality of life. Incorporating resilience-promoting components into diabetes education and re-enforcing these contents every six months are recommended for implementation in clinical practice.

Clinical guideline on magnetically controlled capsule gastroscopy (2021 edition).

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.

Prostate Cancer Susceptibility Loci Identified in GATA2 and ZMIZ1 in Chinese Population.

Background: Common genetic risk variants for prostate cancer (PCa) have been identified at approximately 170 loci using genome-wide association studies (GWAS), most of which were identified in European populations. Recently, GWAS were applied to a large Japanese cohort and identified 12 novel susceptibility loci associated with PCa risk. In this study, we aim to investigate PCa susceptibility loci in the Chinese population. The study data will be used to promote PCa risk control in China. Methods: A total of 235 PCa patients and 252 control subjects (all unrelated) were enrolled in this case-control PCa study. Nine single nucleotide polymorphisms (SNPs) were genotyped in GATA2 (rs73862213, rs2335052, and rs10934857), ZMIZ1 (rs704017, rs77911174, and rs3740259), and SUN2 (rs78397383, rs5750680, and rs138705) genes. The associations between the candidate SNPs and PCa were analyzed using multiple-factor logistic regression and haplotype analysis. Results: The allele frequency distributions of rs73862213 and rs2335052 in the GATA2 gene and rs704017 and rs77911174 in the ZMIZ1 gene were found to be significantly different between PCa cases and controls. Haplotype analysis revealed that the G-C-A haplotype of the GATA2 gene (order of SNPs: rs73862213-rs2335052-rs10934857) and the G-G-G haplotype of the ZMIZ1 gene (order of SNPs: rs704017-rs77911174-rs3740259) were associated with increased PCa risk. None of the SUN2 haplotypes were associated with PCa. Conclusions: Our study data indicates that the minor alleles of rs73862213 and rs2335052 in the GATA2 gene and rs704017 and rs77911174 in the ZMIZ1 gene were associated with increased PCa risk. These findings greatly extended our knowledge of the etiology of PCa.

Overexpression of ELL-associated factor 2 suppresses invasion, migration, and angiogenesis in colorectal cancer.

BACKGROUND: The androgen responsive gene, ELL-associated factor 2 (EAF2), expressed in benign prostate tissues, has been shown to play an important role in tumor suppression in a variety of malignant tumors. In addition, some scholars found that EAF2 frameshift mutations are associated with intratumor heterogeneity in colorectal cancer (CRC) and inactivation of EAF2 in microsatellite instability-high CRC. However, the molecular mechanism by which EAF2 is involved in CRC invasion and metastasis remains unclear. AIM: To determine the clinical value of expression of EAF2 protein in CRC, and to study the effects of EAF2 on the invasion, migration, and angiogenesis of CRC cells in vitro. METHODS: In this study, we collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein in patients with advanced CRC. Subsequently, we investigated the effect of EAF2 on the invasion, migration, and angiogenesis of CRC cells in vitro using plasmid transfection. RESULTS: EAF2 protein was lowly expressed in cancer tissues of patients with advanced CRC. Kaplan-Meier survival analysis showed that the survival rate of the high EAF2 level group was higher than that of the low EAF2 level group. CONCLUSION: Our results demonstrated that EAF2, as a tumor suppressor, may inhibit the invasion, metastasis, and angiogenesis of CRC cells by regulating the signal transducer and activator of transcription 3/transforming growth factor-ß1 crosstalk pathway, and play a cancer suppressive and protective role in the occurrence and development of CRC. Our findings are of great significance to provide a new idea and theoretical basis for the targeted diagnosis and treatment of CRC.

Rapid detection of pathogens using antibody-coated microbeads with bioluminescence in microfluidic chips.

Detection of pathogens was demonstrated in a polydimethylsiloxane (PDMS)/glass microfluidic chip with which microbead-based immunoseparation platform and the bioluminescence technology were integrated. Escherichia coli (E. coli) O157:H7 was used as the model bacteria. The microchamber in microfluidic chip was filled with glass beads coated with antibodies which could capture specific organism, and the capture efficiency of the chip for the bacteria was about 91.75% approximately 95.62%. Then the concentration of bacteria was determined by detecting adenosine triphosphate (ATP) employing bioluminescence reaction of firefly luciferin-lucifera-ATP on chip. The method allowed reliable detection of E. coli O157:H7 concentrations from 3.2 x 10(1) cfu/microL to 3.2 x 10(5) cfu/microL within 20 min. This research demonstrated excellent reproducibility, stability, and specificity, and could accurately detect the pathogenic bacteria in food samples. The microfluidic chip and the equipments used in this method are easy to miniaturize, thus the method has great potential to be developed to a portable device for rapid detection of pathogens.

Identification of the lncRNA-miRNA-mRNA network associated with gastric cancer via integrated bioinformatics analysis.

The aim of the present study was to investigate the long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA regulatory network in gastric cancer (GC) using bioinformatics analysis. Two mRNA gene expression profiles, GSE79973 and GSE54129, and two miRNA expression profiles, GSE93415 and GSE78091, were downloaded from the Gene Expression Omnibus database. The differentially expressed mRNAs (DEMs) and the differentially expressed miRNAs (DEMis) were merged separately. Gene ontology and pathway enrichment analysis were conducted using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was then constructed and the 10 top hub genes in the network were analyzed using the Search Tool for the Retrieval of Interacting Genes. The lncRNA-miRNA-mRNA networks were visualized using Cytoscape software. As a result, 158 shared DEMs (40 upregulated and 118 downregulated) were identified from two mRNA datasets. A total of 30 upregulated miRNAs and 1 downregulated miRNA functioned as DEMis. The PPI network consisted of 129 nodes and 572 interactions. The 10 top hub genes were selected by degree using Cytohubba, including Jun proto-oncogene, mitogen-activated protein kinase (MAPK)3, transforming growth factor-ß1, Fos proto-oncogene, AP-1 transcription factor subunit, interleukin (IL)-8, MAPK1, RELA proto-oncogene nuclear factor-κB subunit, interferon regulatory factor 7, ubiquitin like modifier and vascular endothelial growth factor A. In the lncRNA-miRNA-mRNA network, a total of 1,215 regulatory associations were constructed using Cytoscape. In conclusion, the present study provides a novel perspective of the molecular mechanisms underlying GC by identifying the lncRNA-miRNA-mRNA regulatory network via bioinformatics analysis.

Mechanism and therapeutic effects of Saccharomyces boulardii on experimental colitis in mice.

Inflammatory bowel disease (IBD) is a type of chronic inflammatory disturbance that affects a number of individuals worldwide; the precise mechanism is unclear and treatment is frequently insufficient to maintain patients in remission. Saccharomyces boulardii is a thermophilic, non­pathogenic yeast that may be administered for prophylaxis and treatment of a variety of diarrheal diseases. Recent clinical studies have demonstrated that it may have a role in IBD; however, the mechanism of action is unclear. The hypoxia­inducible factors (HIFs) are ubiquitously expressed regulators of cellular adaptation to hypoxia and are central to the adaptive and inflammatory responses of cells of the intestinal mucosa in patients with IBD. The present study aimed to investigate the effects of S. boulardii on dextran sulfate sodium (DSS)­induced colitis in mice and the effects of S. boulardii on HIFs. Mice were divided into five groups (n=10 mice/group): i) Control; ii) DSS; iii) S. boulardii (Sb) + DSS; iv) normal saline (NS) + DSS; and v) Sb. For 14 consecutive days, mice from the Sb+DSS and Sb groups were given S. boulardii suspension in saline (150 mg/kg/day; final volume 0.2 ml) by oral gavage. The NS+DSS group received the same volume of NS by gavage. The Control mice received water only. From day 8 to day 14, 3.5% DSS was added to the drinking water of the DSS, Sb+DSS and NS+DSS groups to induce acute colitis. Body weight decreased and disease activity index and histological score increased in mice with DSS­induced colitis. Oral administration of S. boulardii reduced DSS­induced weight loss, ameliorated the histological damage and protected the colon barrier in mice with DSS­induced colitis. The expression of HIF­1α and HIF­2α in colon tissues was measured by reverse transcription­quantitative polymerase chain reaction, immunoblotting and immunohistochemistry. The increase in HIFs in the colon induced by DSS was significantly inhibited by S. boulardii treatment. The expression levels of several epithelial­mesenchymal transition (EMT) markers and of vascular endothelial growth factor (VEGF) that are regulated by HIFs were measured. S. boulardii reduced EMT and decreased expression of VEGF that was induced by DSS treatment. These results indicated that treatment with S. boulardii ameliorated DSS­induced colitis, partly through downregulation of HIF­1α and HIF­2α.

Synthesis, Anti-inflammatory Activities and Mechanisms of 3,5- dihydroxycinnamic Acid Derivatives.

BACKGROUND: 3,4-dihydroxycinnamic acid and its derivatives exhibit numerous biologic activities. Such activities have not previously been reported for 3,5-dihydroxycinnamic acid derivatives. In this study, ten derivatives of 3,5- dihydroxycinnamic acid were synthesized and their anti-inflammatory activities were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema. Molecular biological studies have shed lights on their anti-inflammatory mechanism. METHODS: Anti-inflammatory activities of ten new synthesized derivatives of 3,5-dihydroxycinnamic acid were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema, and their anti-inflammatory mechanism was studied by ELISA, real-time RT-PCR, MPO assay and AA-induced mouse ear edema. RESULTS: Compound 7 showed a pronounced anti-inflammatory effect and the inhibition rate was 65.6% at a dose of 1.6mg/ear. This compound acted by reducing mRNA and protein synthesis of tumor necrosis factor-α, interleukins 1ß and 6, and also by decreasing the levels of activated neutrophil infiltrates. Furthermore, compound 7 significantly suppressed arachidonic acid-induced edema as well. Cell-based assays showed that compound 7 inhibited the production of cyclooxygenase- 2-catalyzed prostaglandin E2 from lipopolysaccharide-treated RAW 264.7 cells, and also inhibited 5-lipoxygenase production from A23187-treated RBL-1 cells, and consequently reduced leukotriene B4 production. CONCLUSION: This investigation revealed that some of the derivatives of 3,5-dihydroxycinnamic acid exhibit a more pronounced anti-inflammatory effect than 3,4-dihydroxycinnamic acid. Therefore, 3,5-dihydroxycinnamic acid derivatives, especially compound 7, represent potential value for antiinflammatory drug development.

Expression of pyruvate dehydrogenase is an independent prognostic marker in gastric cancer.

AIM: To investigate the expression and prognostic role of pyruvate dehydrogenase (PDH) in gastric cancer (GC). METHODS: This study included 265 patients (194 male, 71 female, mean age 59 years (range, 29-81 years) with GC who underwent curative surgery at the First Affiliated Hospital of China Medical University from January 2006 to May 2007. All patients were followed up for more than 5 years. Patient-derived paraffin embedded GC specimens were collected for tissue microarrays (TMAs). We examined PDH expression by immunohistochemistry in TMAs containing tumor tissue and matched non-neoplastic mucosa. Immunoreactivity was evaluated independently by two researchers. Overall survival (OS) rates were determined using the Kaplan-Meier estimator. Correlations with other clinicopathologic factors were evaluated by two-tailed χ(2) tests or a two-tailed t-test. The Cox proportional-hazard model was used in univariate analysis and multivariate analysis to identify factors significantly correlated with prognosis. RESULTS: Immunohistochemistry showed that 35.47% of total cancer tissue specimens had cytoplasmic PDH staining. PDH expression was much higher in normal mucosa specimens (75.09%; P = 0.001). PDH expression was correlated with Lauren grade (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001), lymph node metastasis (65.43% with no metastasis vs 51.09% with metastasis; P = 0.033), lymphatic invasion (61.62% with no invasion vs 38.81% with invasion; P = 0.002), histologic subtypes (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001) and tumor-node-metastasis (TNM) stage (39% in poorly differentiated vs 65.91% in well differentiated and 67.11% in moderately differentiated; P = 0.001) in GC. PDH expression in cancer tissue was significantly associated with higher OS (P < 0.001). The multivariate analysis adjusted for age, Lauren classification, TNM stage, lymph node metastasis, histological type, tumor size, depth of invasion and lymphatic invasion showed that the PDH expression in GC was an independent prognostic factor for higher OS (HR = 0.608, 95%CI: 0.504-0.734, P < 0.001). CONCLUSION: Our study indicated that PDH expression is an independent prognostic factor in GC patients and that positive expression of PDH may be predictive of favorable outcomes.

[Effects of mechanical strain on the proliferation of pulmonary epithelial cells and reorganization of integrins].

Using a cyclic strain unit, the proliferation and reorganization of alpha(5), beta(1 ) integrins in human pulmonary epithelial A549 cells that underwent mechanical strain were studied. Flow cytometry revealed that cellular proliferative index reduced significantly after cells were subjected to 15% elongation at frequency 20 cycles/min or 40 cycles/min for 48 h. Confocal microscopy revealed that alpha(5), beta(1 ) integrins in human pulmonary epithelial A549 cells transferred from the apic al layer to the basal layer and created adhesion plaques after 24 h exposure to 15% elongation at frequency 40 cycles/min. It is concluded that alpha(5), beta(1 ) integrins in pulmonary epithelial cells play an important role in transducing mechanical stress into intracellular signals.

[Application of microfluidic-chip in biomedicine].

As a novel analytical technology, the research of Micro total analysis systems (micro-TAS) has been spreading rapidly. micro-TAS has been widely used to perform chemical and biochemical analysis. Microfluidic-based analytical system as micro-TAS's manily direction develops very fast in terms of it's reaction speed, reagent consumption, miniaturization, cost, and automation. After having proven the value of microfluidics for genetic, proteomic and cytomics analysis, this article also anticipates the development tendency of this technology in the biology medicine domain. It has demonstrated that a truly, easy-to-handle Microfluidic-based analytical device will be emerged in the future.