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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.

Wang J.-W.,Shanghai JiaoTong University | Tang Q.-Y.,Shanghai JiaoTong University | Ruan H.-J.,Shanghai JiaoTong University | Cai W.,Shanghai Institute for Pediatric Research
Journal of Pediatric Gastroenterology and Nutrition | Year: 2014

Overweight and obesity may contribute to bone fractures in children; however, the mechanism involved is not clear. In this study, we assessed the relation between serum osteocalcin levels and body composition in obese children. A total of 79 children (ages 7-12 years) were recruited. Serum osteocalcin levels were negatively correlated with fat percentage and visceral fat area (r=-0.24 and r=-0.46, respectively, P<0.05); however, no statistically significant association was found between obesity degree and serum osteocalcin levels (r=-0.29, P=0.052). Serum osteocalcin levels were positively correlated with lean body mass, fat-free mass, and fat-free mass index (r=0.24, 0.23, and 0.31, respectively; P<0.05). In addition, serum osteocalcin levels were significantly lower in severely obese (44.46±9.73 μg/mL) and moderately obese (48.72±10.82 μg/mL) children than in mildly obese (55.43±12.4 μg/mL) and overweight (54.36±11.96 μg/mL) children (P=0.02). These findings indicate that body composition is related to serum osteocalcin levels in overweight and obese children. © 2014 by ESPGHAN and NASPGHAN.

PubMed | Shanghai JiaoTong University and Shanghai Institute for Pediatric Research
Type: Journal Article | Journal: Molecular medicine reports | Year: 2016

Hepatoblastoma is the most common type of malignant liver tumor in children. While outcomes have been greatly improved in the past decades, the treatment of advanced hepatoblastoma has remained challenging. Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group regulators of gene activity, is amplified and overexpressed in a variety of cancers. However, the role of EZH2 in hepatoblastoma has remained to be fully elucidated. The purpose of the present study was to investigate the expression patterns of EZH2 in hepatoblastoma cells and to assess the anticancer effects of EZH2 depletion. Western blot analysis revealed that EZH2 expression was significantly higher in hepatoblastoma specimens compared with that in peritumor tissues, while p27 was reduced in hepatoblastoma. Suppression of EHZ2 using lentiviral small hairpin RNA inhibited hepatoblastoma cell proliferation, induced cell cycle arrest in G1 phase and enhanced the expression of G1/Sphase checkpoint protein p27. These results suggested that EZH2 may represent a potential diagnostic marker and therapeutic target for the treatment of hepatoblastoma.

PubMed | Shanghai JiaoTong University and Shanghai Institute for Pediatric Research
Type: | Journal: Scientific reports | Year: 2016

Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r=-0.50, p<0.05). In ileum, the inflammation grades were inversely associated with farnesoid X receptor (FXR) expression (r=-0.55, p<0.05). In liver, the expression of induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients.

PubMed | University of Hawaii at Manoa, Shanghai JiaoTong University and Shanghai Institute for Pediatric Research
Type: Journal Article | Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | Year: 2016

Biliary atresia (BA) is a severe neonatal cholestasis disease that is caused by obstruction of extra bile ducts. Liver fibrosis progresses dramatically in BA, and the underlying molecular mechanism is largely unknown.Amino acids and biogenic amines were quantified by targeted metabolomic methods in livers of 52 infants with BA and 16 infants with neonatal hepatitis syndrome (NHS). Normal adjacent nontumor liver tissues from 5 hepatoblastoma infants were used as controls. Orthogonal partial least-squares discriminant analysis was used to identify the differences between BA, NHS, and control tissues. Histamine metabolism enzymes and receptors were analyzed by immunohistochemistry and Western blot.The orthogonal partial least-squares discriminant analysis clearly separated BA from NHS and the controls using amino acid and biogenic amine profiles. Histamine was significantly increased in the livers of BA infants and was positively correlated with the severity of fibrosis. This finding was supported by the elevated l-histidine decarboxylase and reduced monoamine oxidase type B expressions in the BA infants with severe fibrosis. Furthermore, histamine receptor H1 was observed in the cholangiocytes of BA livers.Histamine was positively correlated with fibrosis and may be a potential target to prevent liver fibrosis in BA.

PubMed | Shanghai JiaoTong University and Shanghai Institute for Pediatric Research
Type: Journal Article | Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | Year: 2016

Dysregulation of systemic bile acid homeostasis can lead to cholestatic liver diseases and metabolic syndromes. As important anti-inflammatory and immunosuppressive drugs, synthetic glucocorticoids (GCs) are used to treat several cholestatic disorders, including biliary atresia (BA), because of their effects on the regulation of bile acid metabolism. However, the molecular mechanisms that underlie GCs regulation of bile acid homeostasis remain unclear.To provide a mechanistic basis for the effects of GCs on bile acid homeostasis.Male rats were treated with methylprednisolone for 7 days with slow-release osmotic pumps under physiological and cholestatic status that was induced by bile duct ligation (BDL). Expression of glucocorticoid receptor (GR) and genes related to bile acid metabolism was investigated using western blotting, qRT-PCR and immunohistochemistry.We show here that sustained treatment with GCs in rats disrupts the normal changes in systemic bile acid distribution by elevating plasma bile acid levels and reducing faecal bile acid loss. Treatment with GCs stimulated bile acid absorption in the ileum by increasing expression of the apical sodium-dependent bile acid transporter (Asbt). Concomitantly, administration of GCs enhanced liver bile acid uptake by increasing the expression of the major hepatocyte basolateral bile transporter (Ntcp). The reduced expression of a bile acid synthesis rate-controlling enzyme, Cyp7a1, suggests that treatment with GCs suppressed hepatic bile acid synthesis.Our study provides evidence that GCs can increase enterohepatic bile acid circulation through regulation of the biosynthesis and transport of bile salts, which suggests that plasma bile acid levels should be monitored during treatment with GCs in patients with BA.

PubMed | Shanghai JiaoTong University and Shanghai Institute for Pediatric Research
Type: | Journal: Cytokine | Year: 2016

The cytokines tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) have been implicated as important mediators of the inflammatory reaction in patients with intestinal inflammation. The present study was designed to investigate the roles of these cytokines on mucosal barrier function in a mouse model of acute colitis with using anti-cytokine strategies. Mice received 3% dextran sulfate sodium (DSS) in their drinking water for 7days showed morphological alteration of mucosa and increase of intestinal permeability. Administration of IL-6 monoclonal antibody (mAb) or TNF- mAb significantly attenuated intestinal permeability. IL-6 mAb and TNF- mAb treatment also effectively suppressed the expression of claudin-2 and myosin light chain kinase (MLCK). Taken together, we indicated that anti-IL-6 and anti-TNF- therapy prevent intestinal permeability induced by intestinal inflammation.

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