Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition

Kongjiang, China

Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition

Kongjiang, China
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Wang B.,Shanghai JiaoTong University | Li W.,Novartis | Guo K.,Fudan University | Xiao Y.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2012

MicroRNAs, as a kind of negative gene regulators, were demonstrated to be involved in many types of diseases. In this study, we found that transforming growth factor-beta 1 could induce the expression of miR-181a and miR-181b, and miR-181b increased in the much higher folds than miR-181a. Because of the important role of transforming growth factor-beta 1 in HSC activation and liver cirrhosis, we investigate the effect of miR-181a and miR-181b on HSC proliferation. The results showed that miR-181b could promote HSC-T6 cell proliferation by regulating cell cycle. Further study showed p27, the cell cycle regulator, was the direct target of miR-181b in HSC-T6 cell. But miR-181a had no effects on HSC-T6 cell proliferation and cell cycle, and did not target p27. Interestingly, miR-181b is elevated significantly in serum of liver cirrhosis cases comparing to that of normal persons, whereas miR-181a expression was in the similar level with that of normal persons. These results suggested that miR-181b could be induced by TGF-β1 and promote the growth of HSCs by directly targeting p27. The elevation of miR-181b in serum suggested that it may be potential diagnostic biomarkers for cirrhosis. As for miR-181a, it may work in TGF-β1 pathway by a currently unknown mechanism. © 2012 .


Chen Y.,Shanghai JiaoTong University | Chen Y.,Shanghai Institute of Pediatric Research | Chen Y.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | Jie W.,Shanghai Institute of Pediatric Research | And 6 more authors.
Critical Reviews in Eukaryotic Gene Expression | Year: 2012

Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, was belonged to the superfamily of the flavin adenine dinucleotide (FAD)-dependent amine oxidases. LSD1 specifically demethylates mono or dimethylated dimethylated histone H3 lysine4 (H3K4) and H3 lysine 9 (H3K9) via a redox process. Recently evidences showed that LSD1 played an important role in a broad spectrum of biological processes, including cell proliferation, adipogenesis, spermatogenesis, chromosome segregation and embryonic development. Furthermore, LSD1 also could promote progress of tumor by inhibiting the tumor suppressor activity of p53. To date, as a potential drug for discovering anti-tumor drugs, the medical significance of LSD1 inhibitors have been greatly appreciated. Here, we reviewed the remarkable progress being made in understanding of LSD1, mainly on its structure, basic function and medical application in tumor therapy. © 2011 Begell House, Inc.


Qian L.,Shanghai JiaoTong University | Qian L.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | Wang B.,Shanghai JiaoTong University | Tang N.,Shanghai JiaoTong University | And 3 more authors.
Early Human Development | Year: 2012

The variability of breast-milk zinc concentration is high among breastfeeding women, and it is known to be independent of dietary zinc intake. As a result, transient neonatal zinc deficiency is not rare in the breastfed infants due to low milk zinc concentration in their breastfeeding mothers. Up to now, SLC30A2 has been documented the only candidate gene showing correlation with human milk zinc trait. In this study, 750 breastfeeding women were recruited and 10. ml foremilk was collected on 42nd postpartum day. The milk zinc concentration was measured, and genomic DNA was isolated from breast-milk. Direct sequencing and Taqman assay were used to identify the SLC30A2 polymorphisms associated with low-milk-zinc. Subsequently, the factors associated with breast-milk zinc were investigated using regression model. The correlation study showed that SLC30A2/-697G > T and SLC30A2/1031A > G polymorphisms were associated with low-milk-zinc in our subjects. These two polymorphisms explained 3.23% of total variance in milk zinc level. For non-genetic variables, the obese breastfeeding women (BMI > 25) secreted less zinc into their breast-milk. The variation of milk zinc was independent of pregnant age, birth weight, infant gender, cesarean delivery, preterm delivery and vitamin D supplementation. In conclusion, our results indicated that - 697 G > T and 1031A > G polymorphisms in the SLC30A2 gene may be associated with low-milk-zinc in Chinese breastfeeding women. Maternal BMI is significantly correlated with milk zinc level in negative manner. Our study demonstrated that both genetic and non-genetic factors could modulate milk zinc level. © 2012 Elsevier Ireland Ltd.


Cai W.,Shanghai JiaoTong University | Cai W.,Shanghai Institute for Pediatric Research | Cai W.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2014

Purpose of review: This review is to explore the childhood nutrition and health in relation to socioeconomic changes in transitional countries, and to describe the good experiences and policies in these countries to combat childhood nutritional challenges. RECENT FINDINGS: Double burden of malnutrition - the coexistence of under-nutrition and over-nutrition in the same population - is a prominent public health concern in transitional countries. With rapid industrialization, these countries are facing a growing epidemic of overweight/obesity in children and adolescents. The increasing prevalence of childhood overweight/obesity is a likely consequence of behavioral changes, and accompanied with an increasing incidence of noncommunicable chronic diseases. Although remarkable improvement of childhood nutrition was achieved, the stunting growth and micronutrient deficiency remain to be child health issues in transitional countries. SUMMARY: The social transition caused a broad range of nutrition-associated problems. Previous successful experiences indicated that if appropriate action is undertaken, the child nutritional problems accompanied with economic transition could be controlled to some extent. However, greater efforts are needed to improve the status of childhood nutrition in transitional countries. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Wu J.,Shanghai JiaoTong University | Wu J.,Shanghai Institute for Pediatric Research | Wu J.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | Huang C.,Shanghai JiaoTong University | And 6 more authors.
Nutrition | Year: 2013

Objectives: Cancer cachexia is associated with impaired nutritional status and systemic inflammation. The goal of this study was to evaluate the nutritional status and resting energy expenditure (REE) changes in patients with newly detected esophageal cancer, and the influence of weight loss on REE. Methods: Fifty-six patients and 30 healthy controls were prospectively enrolled, and patients were further divided into weight-stable (WS) and weight-loss (WL) subgroups. Body composition, measured REE (mREE), and the ratio of mREE to predicted REE (pREE) by Harris-Benedict formula were assessed. Blood levels of hemoglobin, albumin, prealbumin, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6 were measured in patients. Results: Cancer patients had lower body mass index (BMI) and percentage of fat mass, but higher mREE and percentage of mREE/pREE compared with healthy controls (P<0.05). WS (n=32) and WL patients (n=24) had similar BMI and body composition indices, but the latter had obviously higher mREE, mREE per kilogram body weight (mREE/BW), percentage of mREE/pREE, hs-CRP and IL-6 levels, and lower albumin and prealbumin levels. Percentage of weight loss was positively correlated with REE/BW, hs-CRP, and IL-6 level (r=0.238, P=0.044; r=0.446, P=0.01; r=0.196, P=0.047, respectively). Conclusion: Impaired nutrition status, elevated energy expenditure, and higher inflammation status tend to be apparent in weight-losing patients with newly diagnosed esophageal cancer, which suggested that early recognition of body weight change and routine nutritional risk screening followed by adequate nutrition intervention should be applied in these patients. © 2013 Elsevier Inc.


Xiao Y.,Shanghai Institute for Pediatric Research | Xiao Y.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | Qu C.,Shanghai JiaoTong University | Ge W.,Shanghai JiaoTong University | And 5 more authors.
Cellular Physiology and Biochemistry | Year: 2014

Background & Aims: It has recently been reported that thymosin beta-4 (Tβ4) has anti-fibrogenic effects in human hepatic stellate cells (HSCs) in vitro, but the mechanisms underlying these effects remain unclear. The aim of this study was to investigate the roles of Tβ4 in the proliferation, migration, and activation of HSCs. Methods: Enzyme-linked immunosorbent assays (ELISA), immunohistochemistry, and western blot assays were utilized to determine the expression levels of Tβ4 in serum, liver tissues, and LX-2 cells. Tβ4 was depleted in LX-2 cells using small interfering RNAs (siRNAs). Cell proliferation was analyzed using cell counting kit-8 (CCK-8) viability assays, and cell migration was investigated using wound-healing and transwell migration assays. Results: The expression of Tβ4 was significantly reduced during the progression of liver fibrosis. The depletion of Tβ4 significantly promoted the proliferation and migration of LX-2 cells via the activation of the PI3K/Akt signaling pathway. The pro-migratory and pro-proliferative effects of Tβ4 depletion in LX-2 cells can be counteracted by treatment with the Akt inhibitor MK-2206. In addition, Tβ4 depletion was also associated with the activation of HSCs via the enhanced expression of α-smooth muscle actin (α-SMA) and vimentin. Conclusions: Our results suggest that Tβ4 participates in liver fibrosis by inhibiting the migration, proliferation, and activation of HSCs and that Tβ4 may be an effective target in the treatment of liver fibrosis. © 2014 S. Karger AG, Basel.


Yang K.,Shanghai JiaoTong University | Yang K.,Shanghai Institute for Pediatric Research | Yang K.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | Cai W.,Shanghai JiaoTong University | And 4 more authors.
Journal of Molecular Endocrinology | Year: 2012

Maternal high-fat (HF) diets during gestation and lactation have been shown to contribute to metabolic disorders in offspring. Molecular and epigenetic mechanisms underlying this connection may be essential for the prevention and treatment of the fetal origins of metabolic diseases. The current study examined the impact of maternal HF diets on Wnt signaling and histone modification in offspring. Time-pregnant Sprague-Dawley rats were fed either control diet or HF diet during gestation and lactation and then the neonatal offspring of both groups were investigated. The neonatal offspring born to dams fed on HF diets exhibited increases in serum glucose and liver triglyceride levels. Maternal exposure to the HF diet also repressed the mRNA expression of Wnt1 and nuclear β-catenin protein in the liver of offspring. The altered Wnt1 gene expression may be due to the changes of acetylation of H4 at its promoter as well as acetylation of H4 and methylation of H3K9 at coding region. Maternal exposure to the HF diet induced suppression of the Wnt/β-catenin signaling pathway through histone modification, potentially increasing the risk of metabolic syndrome. © 2012 Society for Endocrinology.


Chen Y.,Shanghai JiaoTong University | Chen Y.,Shanghai Institute of Pediatric Research | Chen Y.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | Ge W.,Shanghai JiaoTong University | And 6 more authors.
International Journal of Molecular Medicine | Year: 2012

Intestinal fibrosis is one of the major serious complications of Crohn's disease (CD). However, there are no effective antifibrotic drugs to treat intestinal fibrosis in CD. Therefore, it is important to understand the pathogenesis of fibrosis in CD. It has been reported that members of the miR-200 family are essential in the regulation of renal fibro-genesis. In this study, we analyzed the function of miR-200a and miR-200b in intestinal fibrosis, which was induced by transforming growth factor β1 (TGF-β1) in vitro. Furthermore, we detected the expression of miR-200a and miR-200b in CD specimens, which were divided into groups of fibrosis and no-fibrosis. The results of this study showed that administration of miR-200b could partially protect intestinal epithelial cells from fibrogenesis invitro. Furthermore, we found that miR-200b was overexpressed in the serum of the fibrosis group. The results suggest that miR-200b has potential value for diagnostic and therapeutic applications for CD patients with fibrosis complications.


Xiao Y.,Shanghai JiaoTong University | Xiao Y.,Shanghai Institute of Pediatric Research | Xiao Y.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | Wang J.,Shanghai JiaoTong University | And 16 more authors.
Journal of Hepatology | Year: 2015

Background & Aims Cholestatic liver disease is associated with dysregulated expression of microRNAs (miRNAs). However, it remains unknown whether miRNAs are involved in the cholestasis-induced proliferation of cholangiocytes. In this study, we tested the hypothesis that miRNAs modulate cholangiocyte proliferation through effects on the IL-6 pathway, a known regulator of cholangiocyte proliferation. Methods Expression of IL-6, Foxa2, and phosphorylated signal transducer activator of transcription 3 (STAT3) was investigated in patients with biliary atresia (BA) and in rats subjected to bile duct ligation (BDL). miRNA expression was determined in BA patients and BDL rats, with miRNA array and quantitative real-time PCR. Biological functions of miRNAs were studied using immunoblot, immunohistochemical and proliferation assays. Luciferase reporter assays and Western blots were performed to identify miRNA targets. Results Hepatic interleukin-6 (IL-6) expression was significantly elevated in BA patients and BDL rats, while the expression of miR-124 was dramatically decreased in comparison to controls. Moreover, mRNA levels of STAT3 and IL-6 receptor (IL-6R) were inversely correlated with those of miR-124. Ectopic expression of miR-124 inhibited IL-6-mediated cholangiocyte proliferation in vitro and cholangiocyte hyperplasia in vivo, through a mechanism involving direct targeting of the 3'-untranslated region of STAT3 and IL-6R. We further demonstrated that miR-200 family members were significantly upregulated in cholestasis and inhibited FOXA2 expression in cholangiocytes, which further enhanced the expression of IL-6. Conclusions Our findings suggest that downregulation of miR-124 and upregulation of miR-200 collaboratively promote bile duct proliferation through the IL-6/STAT3 pathway.


Sheng Q.,Shanghai JiaoTong University | Sheng Q.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | Lv Z.,Shanghai JiaoTong University | Cai W.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition | And 5 more authors.
Pediatric Research | Year: 2014

Background: The aim of this study was to investigate the effects of human β-defensin-3 (hBD3) on intestinal wound healing and in a neonatal rat model of necrotizing enterocolitis (NEC). Methods: Enterocyte migration and proliferation were detected in vitro and in vivo. The role of chemokine receptor CCR6 and its downstream signaling pathway was assessed. Newborn Sprague-Dawley rats were randomly divided into four groups: Control+NS, Control+hBD3, NEC+NS, and NEC+hBD3. Body weight, histological score, survival time, cytokines expression, and mucosal integrity were evaluated. Results: hBD3 could stimulate enterocyte migration, but not proliferation, both in cultured enterocytes and in the NEC model. Neutralizing antibody and small interfering RNA confirmed this stimulatory effect was mediated by CCR6. Furthermore, hBD3 induced Rho activation, myosin light chain 2 phosphorylation, and F-actin accumulation. The bactericidal activity of hBD3 was maintained throughout a broad pH range. Strikingly, hBD3 administration decreased the incidence of NEC, increased the survival rate, and reduced the severity of NEC. Moreover, hBD3 reduced the proinflammatory cytokines expression in ileum and serum and preserved the intestinal barrier integrity. Conclusion: This study provided evidence that the antimicrobial peptide hBD3 might participate in intestinal wound healing by promoting enterocyte migration and show beneficial effects on newborn rats with NEC. Copyright © 2014 International Pediatric Research Foundation, Inc.

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