MiR-198 affects the proliferation and apoptosis of colorectal cancer through regulation of ADAM28/JAK-STAT signaling pathway.

OBJECTIVE: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. microRNA-198 (miR-198) was reported to be a tumor suppressive miRNA but its role in CRC is largely unknown. Thus, we aimed to investigate the role of miR-198 and its downstream signaling pathway in CRC. PATIENTS AND METHODS: Quantitative Real-time PCR was conducted to measure miR-198 expression in human CRC cell lines (SW620, SW480 and HT29) and normal colon cell line (FHC). Using MTT, colony formation and flow cytometry assay, we investigated the effects of miR-198 on cell proliferation, colony formation and apoptosis. Luciferase activity reporter assay and Western blot assay were performed to validate the target of miR-198. Using Western blot assay, we detected the protein levels of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. RESULTS: The results showed that miR-198 expression was significantly reduced in CRC cell lines compared with FHC. Overexpression of miR-198 inhibits CRC cell proliferation and colony formation but promotes apoptosis. Further study revealed ADAM metallopeptidase domain 28 (ADAM28) was a direct target of miR-198, and the overexpression of ADAM28 reversed the effects of miR-198 on cell behaviors. Besides that, miR-198 blocks the JAK/STAT pathway through regulating ADAM28. CONCLUSIONS: These results collectively revealed miR-198 inhibited cell proliferation but promoted apoptosis through targeting ADAM28 and blocking JAK/STAT pathway in CRC cells.

[Chronic liver disease increases with damage to intestinal barrier function].

Objective: To probe into the correlation between chronic liver disease and intestinal barrier function. Methods: 1 491 cases of hospitalized patients were enrolled, of which 741 cases were of chronic liver diseases, including 397 cases of fatty liver diseases, 230 cases of chronic hepatitis, 114 cases of liver cirrhosis, and 750 cases of non-hepatic diseases. All admitted patients' intestinal barrier function like diamine oxidase (DAO), D-lactate, lipopolysaccharide, and biochemical indicators of liver functions were tested. According to different data, statistical analysis was done using t-test, ANOVA, Dunnett's test, χ (2) test of fourfold table, Pearson's correlation, and binary logistic regression. Results: The intestinal barrier dysfunction was more likely to occur in the chronic liver disease group than that of non-hepatic disease group [54.15% (379/741) vs. 18.53% (139/750), χ (2) = 193.58, P < 0.001]. The correlation analysis between biochemical indicators of liver function and intestinal barrier function in chronic liver disease group showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and total bilirubin levels were more susceptible to intestinal barrier dysfunction than those with normal indexes (P < 0.05 ). GGT had stimulated DAO (P < 0.05, OR > 1), D-lactate (P < 0.05, OR > 1), lipopolysaccharide (P < 0.05, OR > 1), ALT and AST. Conclusion: Chronic liver disease increases with damage to intestinal barrier function.

[Ras-associated autoimmune leukoproliferative disorder: a report of 2 cases and literature review].

Objective: To investigate the clinical features and genetic characteristics of cases with Ras-associated autoimmune leukoproliferative disorder(RALD). Method: Characteristics of clinical data and gene mutation of the first two cases in China with RALD were retrospectively analyzed. The related literature was searched by using search terms "NRAS" , "KRAS" or "RALD" . Result: Case1, a seven-year-seven-month old girl, was admitted due to "thrombocytopenia and splenomegaly for three years" . Palpation showed enlargement of submandibular lymph nodes and hepatosplenomegaly.The platelet count fluctuated between 15×10(9)/L and 60×10(9)/L. Hemoglobin was as 57 g/L and Coomb's test was positive.Lung computed tomography revealed interstitial lung disease, bilateral pleural effusion, pericardial effusion, myocardial injury and ascites. Case2, a seven-year-five-month old girl, was admitted due to "recurrent thrombocytopenia for seven years, intermittent eyelid and abdominal swelling for three years" . Palpation showed enlargement of cervical and right inguinal lymph nodes, and hepatosplenomegaly.The number of platelet and monocyte were 9×10(9)/L and 5.46×10(9)/L, respectively. Bone marrow smear revealed an increase in the proportion of primitive immature cells (0.09 to 0.11). Lung computed tomography revealed interstitial lung disease, pericardial effusion, cardiac enlargement and pulmonary hypertension. The gene sequencing results showed KRAS gene c.38G> A somatic mutation in case1, and p.G12D and NRAS gene c.38G> A, p.G13D somatic mutation in case2. A total of 8 reports were retrieved including 23 cases caused by NRAS(10 cases) or KRAS(13 cases) gene somatic mutation. All the 23 cases showed hypergammaglobulinemia, splenomegaly, B cells hyperplasia or mononucleosis. Conclusion: RALD often manifests as hepatosplenomegaly,lymphoproliferation, autoimmune hematocytopenia, B cells hyperplasia or mononucleosis, hypergammaglobulinemia. Gene sequencing analysis can help diagnose the disease.

[Influence of gut microecology on the pathogenesis and treatment of nonalcoholic fatty liver disease].

OBJECTIVE: To establish a rat model of nonalcoholic fatty liver disease (NAFLD) using high-fat diet, and to dynamically observe the influence of the changes in gut microbiota on the development and progression of NAFLD in rats during and after modeling. METHODS: Sprague-Dawley rats were given high-fat diet to establish the model of NAFLD, and these rats were randomly divided into high-fat group, antibiotic pretreatment group, antibiotic treatment group, restricted diet group, and control group. The rats were sacrificed in different feeding periods, and 16sRNA fluorescent quantitative PCR was used to analyze the changes in ileocecal microbiota in rats. The liver pathological scores were determined, and enzymatic colorimetry was used to measure blood lipid level in serum and liver homogenate. The sample mean t-test was used for comparison between groups. RESULTS: Compared with the high-fat group, the restricted diet group showed the most significant improvements in quality of life and biochemical parameters. In the restricted diet group, the number of probiotics (Bifidobacterium and Lactobacillus) at the end of the ileum gradually increased and tended to increase over the time of intervention, and the most significant difference between this group and the high-fat group occurred at the 10th week (Bifidobacterium: 0.91±0.23 vs 0.28±0.12, P < 0.05; Lactobacillus: 0.78±0.04 vs 0.21±0.03, P < 0.05), while the number of enterococci decreased. There were no significant differences in enteric bacilli between groups (all P > 0.05). At the 10th week, the liver pathological scores in the control group, antibiotic treatment group, and restricted diet group were 1.13±1.74, 4.86±0.86, and 2.94±1.91, respectively, significantly lower than 7.09±2.03 in the high fat group (all P < 0.05). CONCLUSION: Diet structure change and antibiotic intervention can adjust gut microecology, alleviate the lesions of NAFLD, and thus provide new strategies for the prevention and treatment of NAFLD from the perspective of microecology.