miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma.

Gallbladder cancer (GBC) is the most common malignant tumour of the biliary track system. Angiogenesis plays a pivotal role in the development and progression of malignant tumours. miR-143-3p acts as a tumour suppressor in various cancers. Their role in GBC is however less well defined. Here we show that the expression levels of miR-143-3p were decreased in human GBC tissues compared with the non-tumour adjacent tissue (NAT) counterparts and were closely associated with overall survival. We discovered that miR-143-3p was a novel inhibitor of tumour growth and angiogenesis in vivo and in vitro. Our antibody array, ELISA and PLGF rescue analyses indicated that PLGF played an essential role in the antiangiogenic effect of miR-143-3p. Furthermore, we used miRNA target-prediction software and dual-luciferase assays to confirm that integrin α6 (ITGA6) acted as a direct target of miR-143-3p. Our ELISA and western blot analyses confirmed that the expression of PLGF was decreased via the ITGA6/PI3K/AKT pathway. In conclusion, miR-143-3p suppresses tumour angiogenesis and growth of GBC through the ITGA6/PI3K/AKT/PLGF pathways and may be a novel molecular therapeutic target for GBC.

Relación entre la expresión de IL-2 e IL-4 y sus polimorfismos y los riesgos de padecer infección por Mycoplasma pneumoniae y asma en niños / Associations of IL-2 and IL-4 Expression and Polymorphisms With the Risks of Mycoplasma pneumoniae Infection and Asthma in Children

Introducción: El asma es una afección inflamatoria de las vías respiratorias. Las infecciones porMycoplasma pneumoniae pueden exacerbar los síntomas del asma. Se ha demostrado que la interleucina2 y la interleucina4 participan en las reacciones inmunitarias e inflamatorias. Hemos estudiado la relación entre los polimorfismos de la IL2 y la IL4 y su expresión y el riesgo de padecer asma e infección por M.pneumoniae en niños. Métodos: Se reclutó a 392 niños asmáticos y 849 controles para el estudio. Se genotiparon 8 polimorfismos en IL2 e IL4 con la plataforma MassARRAY de Sequenom. La infección por M.pneumoniae y el número de copias se establecieron mediante PCR fluorescente. Los niveles séricos de expresión de IL-2 e IL-4 se midieron con ELISA. Resultados: Hallamos una relación significativa entre el polimorfismo rs6534349 de IL2 y el aumento de riesgo de sufrir asma (heterocigóticos, p = 0,029; variantes homocigóticas, p = 0,013), así como entre el polimorfismo rs2227284 de IL4 y una reducción del riesgo de padecer asma (heterocigóticos, p = 0,026; variantes homocigóticas, p = 0,001). Además, la relación con otros polimorfismos, excepto el rs2070874, se hizo evidente al agrupar a los niños asmáticos según la clasificación GINA de control y gravedad del asma. Asimismo, los niveles séricos de expresión de IL-2 e IL-4 fueron significativamente mayores en los sujetos no infectados (p = 0,038) e infectados (p = 0,011) por M.pneumoniae, respectivamente. Esta observación también se cumple entre los pacientes asmáticos (p = 0,016 para IL-2 y p = 0,042 para IL-4), pero en los controles no asmáticos solo se cumple en el caso de la IL-4 (p = 0,032). Del mismo modo, observamos que el genotipo GG rs6534349 estaba claramente relacionado con un aumento de las posibilidades de tener una infección con alta carga de M.pneumoniae (p = 0,0376). Conclusiones: La IL2 y la IL4 podrían ser biomarcadores importantes para calcular el riesgo de padecer asma, así como infección por M.pneumoniae, en niños

Introduction: Asthma is an inflammatory disorder of the airways and the symptoms of asthma could be exacerbated by Mycoplasma pneumoniae infection. Interleukin-2 and interleukin-4 have been implicated in immune and inflammatory reactions. We examined the associations of IL2 andIL4 polymorphisms and expression with the risks of asthma and M. pneumoniae infection in children. Methods: 392 asthmatic children and 849 controls were recruited into the study. Eight polymorphisms inIL2 and IL4 were genotyped with Sequenom MassARRAY platform. M. pneumoniae infection and copy number was determined with fluorescence PCR. IL-2 and IL-4 serum expression levels were determined by using ELISA. Results: We found a significant association of IL2 rs6534349 polymorphism with increased asthma risk (heterozygotes, P = .029; homozygous variants; P = .013) and of IL4 rs2227284 polymorphism with reduced asthma risk (heterozygotes, P = .026; homozygous variants; P = .001). Besides, the association of other polymorphisms, except rs2070874 polymorphism, became apparent when the asthmatic children were grouped according to GINA classification of asthma control and severity. In addition, IL-2 and IL-4 serum expression levels were significantly higher in M. pneumoniae negative (P = .038) and positive (P = .011) subjects respectively. This observation holds true among asthmatic patients (P = .016 for IL-2 and P = .042 for IL-4), but only the IL-4 observation remained correct among non-asthmatic controls (P = .032). We also observed that the rs6534349 GG genotype was significantly associated with increased odds of getting high load M. pneumoniae infection (P = .0376). Conclusions: IL2 and IL4 could be important biomarkers for estimating the risks of asthma and M. pneumoniae infection in children

Early and late Iron supplementation for low birth weight infants: a meta-analysis.

BACKGROUND: Iron deficiency in infancy is associated with a range of clinical and developmentally important issues. Currently, it is unclear what is the optimal timing to administer prophylactic enteral iron supplementation in preterm and very low birth weight infants. The objective of this meta-analysis was to evaluate early compared with late iron supplementation in low birth weight infants. METHODS: PubMed and Cochrane Library databases were searched up to May 10, 2014 for studies that compared the benefit of early and late iron supplementation in infants of low birth weight. Sensitivity analysis was carried out using the leave one-out approach and the quality of the included data was assessed. RESULTS: The data base search and detailed review identified four studies that were included in the meta-analysis. The number of included patients was 246 (n=121 for early supplementation and n=125 for late supplementation) and the majority were premature infants. Across studies, early supplementation ranged from as early as enteral feeding was tolerated to 3 weeks, and late supplementation ranged from 4 weeks to about 60 days. Early treatment was associated with significantly smaller decreases in serum ferritin and hemoglobin levels (P<0.001). In addition, the rate of blood transfusions was lower with early compared with late iron supplementation (P=0.022). There was no difference between early and late supplementation in the number of patients with nectorizing enteroclitis (>bell stage 2) (P=0.646). Sensitivity analysis indicated no one study overly influenced the findings and that the data was reliable. CONCLUSION: In conclusion, early iron supplementation resulted in less a decrease in serum ferritin and hemoglobin levels in infants with low birth rate. However, caution should be used when treating infants with iron so as not to result in iron overload and possibly negative long-term effects on neurodevelopment.

Associations of IL-2 and IL-4 Expression and Polymorphisms With the Risks of Mycoplasma pneumoniae Infection and Asthma in Children.

INTRODUCTION: Asthma is an inflammatory disorder of the airways and the symptoms of asthma could be exacerbated by Mycoplasma pneumoniae infection. Interleukin-2 and interleukin-4 have been implicated in immune and inflammatory reactions. We examined the associations of IL2 and IL4 polymorphisms and expression with the risks of asthma and M. pneumoniae infection in children. METHODS: 392 asthmatic children and 849 controls were recruited into the study. Eight polymorphisms in IL2 and IL4 were genotyped with Sequenom MassARRAY platform. M. pneumoniae infection and copy number was determined with fluorescence PCR. IL-2 and IL-4 serum expression levels were determined by using ELISA. RESULTS: We found a significant association of IL2 rs6534349 polymorphism with increased asthma risk (heterozygotes, P=.029; homozygous variants; P=.013) and of IL4 rs2227284 polymorphism with reduced asthma risk (heterozygotes, P=.026; homozygous variants; P=.001). Besides, the association of other polymorphisms, except rs2070874 polymorphism, became apparent when the asthmatic children were grouped according to GINA classification of asthma control and severity. In addition, IL-2 and IL-4 serum expression levels were significantly higher in M. pneumoniae negative (P=.038) and positive (P=.011) subjects respectively. This observation holds true among asthmatic patients (P=.016 for IL-2 and P=.042 for IL-4), but only the IL-4 observation remained correct among non-asthmatic controls (P=.032). We also observed that the rs6534349 GG genotype was significantly associated with increased odds of getting high load M. pneumoniae infection (P=.0376). CONCLUSIONS: IL2 and IL4 could be important biomarkers for estimating the risks of asthma and M. pneumoniae infection in children.

Non-alcoholic fatty liver disease: An early mediator predicting metabolic syndrome in obese children?

AIM: To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and if liver B-ultrasound can be used for its diagnosis. METHODS: We classified 861 obese children (6-16 years old) into three subgroups: group 0 (normal liver in ultrasound and normal transaminases); group 1 (fatty liver in ultrasound and normal transaminases); and group 2 (fatty liver in ultrasound and elevated transaminases). We measured the body mass index, waist and hip circumference, blood pressure, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI), lipid profile and transaminases in all the participants. The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination. RESULTS: Among the 861 obese children, 587 (68.18%) were classified as having NAFLD, and 221 (25.67%) as having MS. The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587), which was much higher than that in non-NAFLD group (group 0, 12.04%) (P < 0.01). There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05). The incidence of NAFLD in MS patients was 84.61% (187/221), which was significantly higher than that of hypertension (57.46%, 127/221) and glucose metabolic anomalies (22.62%, 50/221), and almost equal to the prevalence of dyslipidemia (89.14%, 197/221). Based on the B-ultrasound scales, the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR): 2.18, 95% confidence interval (95% CI): 1.27-3.75], dyslipidemia (OR: 7.99, 95% CI: 4.34-14.73), impaired fasting glucose (OR: 3.65, 95% CI: 1.04-12.85), and whole MS (OR: 3.77; 95% CI: 1.90-7.47, P < 0.01). The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased. CONCLUSION: NAFLD is not only a liver disease, but also an early mediator that reflects metabolic disorder, and liver B-ultrasound can be a useful tool for MS screening.

Non-organ-specific preventive effect of long-term administration of Korean red ginseng extract on incidence of human cancers.

Previously, two case-control studies and a cohort study strongly suggested that Panax ginseng C.A. Meyer exerted non-organ-specific preventive effects against cancer. The purpose of the present study was to evaluate the effects of red ginseng extract on the incidence of human primary cancer. We conducted a randomized, double-blinded, placebo-controlled trial on 643 chronic atrophic gastritis patients in four hospitals in Zhejiang Province, China. Red ginseng extract powder (1 g) was administered orally to each patient per week for 3 years and followed up for 8 years. The development of various cancers in the red ginseng subjects was compared to that of a placebo group. The red ginseng extract powder was specified in terms of its components. Twenty-four cancers of various organs were diagnosed from these subjects during the 11 years: eight lung cancers, six stomach cancers, two liver cancers, two colorectal cancers, and one cancer each of the nasopharynx, esophagus, pancreas, urinary bladder, prostate, and gallbladder. The red ginseng group, which included both genders, demonstrated a relative cancer risk of 0.54 (95% confidence interval, 0.23-1.28; P = .13) compared to the placebo group, which was not statistically significant. Among the 24 cancer patients, 21 were male. The male red ginseng group showed a relative cancer risk of 0.35 (95% confidence interval, 0.13-0.96; P = .03) compared to the male placebo group, which was highly significant statistically. In the present clinical trial on chronic atrophic gastritis patients, administration of red ginseng extract powder for 3 years exerted significant preventive effects on the incidence of non-organ-specific human cancers in males.

Nested case-control study on the risk factors of colorectal cancer.

AIM: To investigate the risk factors of colon cancer and rectal cancer. METHODS: A nested case-control study was conducted in a cohort of 64 693 subjects who participated in a colorectal cancer screening program from 1989 to 1998 in Jiashan county, Zhejiang, China. 196 cases of colorectal cancer were detected from 1990 to 1998 as the case group and 980 non-colorectal cancer subjects, matched with factors of age, gender, resident location, were randomly selected from the 64 693 cohort as controls. By using univariate analysis and multivariate conditional logistic regression analysis, the odds ratio (OR) and its 95 % confidence interval (95 %CI) were calculated between colorectal cancer and personal habits, dietary factors, as well as intestinal related symptoms. RESULTS: The multivariate analysis results showed that after matched with age, sex and resident location, mucous blood stool history and mixed sources of drinking water were closely associated with colon cancer and rectal cancer, OR values for the mucous blood stool history were 3.508 (95 %CI: 1.370-8.985) and 2.139 (95 %CI: 1.040-4.402) respectively; for the mixed drinking water sources, 2.387 (95 %CI: 1.243-4.587) and 1.951 (95 %CI: 1.086-3.506) respectively. All reached the significant level with a P-value less than 0.05. CONCLUSION: The study suggested that mucous blood stool history and mixed sources of drinking water were the risk factors of colon cancer and rectal cancer. There was no any significant association between dietary habits and the incidence of colorectal cancer.

Reduction of the incidence and mortality of rectal cancer by polypectomy: a prospective cohort study in Haining County.

AIM: To reduce the incidence and mortality of rectal cancer and address the hypothesis that colorectal cancer often arise from precursor lesion(s), either adenomas or non-adenomatous polyps, by conducting a population-based mass screening for colorectal cancer in Haining County, Zhejiang, PRC. METHODS: From 1977 to 1980, physicians screened the population of Haining County using 15 cm rigid endoscopy. Of over 240000 participants, 4076 of them were diagnosed with precursor lesions, either adenomas or non-adenomatous polyps, which were then removed surgically. All individuals with precursor lesions were followed up and reexamined by endoscopy every two to five years up to 1998. RESULTS: After the initial screening, 953 metachronous adenomas and 417 non-adenomatous polyps were detected and removed from the members of this cohort. Further, 27 cases of colorectal cancer were detected and treated. Log-rank tests showed that the survival time among those cancer patients who under went mass screening increased significantly compared to that of other colorectal cancer patients (P<0.0001). According to the population-based cancer registry in Haining County, age-adjusted incidence and mortality of rectal cancer decreased by 41% and 29% from 1977-1981 to 1992-1996, respectively. Observed cumulative 20-year rectal cancer incidence was 31% lower than the expected in the screened group; the mortality due to rectal cancer was 18% lower than the expected in the screened group. CONCLUSION: Mass screening for rectal cancer and precursor lesions with protocoscopy in the general population and periodical following-up with routine endoscopy for high-risk patients may decrease both the incidence and mortality of rectal cancer.