12 results on '"Xiao, Yongtao"'
Search Results
2. Heterozygous Actg2R257C mice mimic the phenotype of megacystis microcolon intestinal hypoperistalsis syndrome.
- Author
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Cai, Hui, Xiao, Yongtao, Chen, Shanshan, Lu, Ying, Du, Jun, You, Yaying, Zhu, Jing, Zhou, Jie, Cai, Wei, and Wang, Ying
- Subjects
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SMOOTH muscle contraction , *GENETIC variation , *INTESTINES , *MICE , *MISSENSE mutation - Abstract
Background: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare and serious congenital disorder with poor outcomes, where a heterozygous missense mutation is present in the ACTG2 gene. Here, we aimed to investigate the pathogenesis of ACTG2 in MMIHS. Methods: A cohort with 20 patients with MMIHS was screened. Actg2R257C heterozygous mutant mice were generated using the CRISPR/Cas9 system. Gastrointestinal (GI) motility, voluntary urination, collagen gel contraction, and G‐actin/F‐actin analysis were performed. Key Results: The R257C variant of ACTG2 most frequently occurred in patients with MMIHS and demonstrated the typical symptoms of MMIHS. Actg2R257C heterozygous mutant mice had dilated intestines and bladders. The functional assay showed a prolonged total time of GI transit and decreased urine spot area. Collagen gel contraction assay and G‐actin/F‐actin analysis indicated that mutant mice showed reduced area of contraction of smooth muscle cells (SMCs) and impaired actin polymerization. Conclusions & Inferences: A mouse model demonstrating MMIHS‐like symptoms was generated. The Actg2R257C heterozygous variant impairs SMCs contraction by interfering with actin polymerization, leading to GI motility disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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3. Lactobacillus plantarum supplementation alleviates liver and intestinal injury in parenteral nutrition‐fed piglets.
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Wang, Weipeng, Wang, Ying, Liu, Yang, Tian, Xinbei, Chen, Shanshan, Lu, Ying, Wu, Bo, Xiao, Yongtao, and Cai, Wei
- Abstract
Objective: Long‐term parenteral nutrition (PN) causes PN‐associated liver disease, for which therapeutic approaches are limited. This study aimed to investigate the effects of Lactobacillus plantarum CGMCC 1258 (LP) on liver and intestinal injury in PN‐fed neonatal piglets. Methods: The piglets received PN with or without oral LP for 14 days. The levels of liver enzymes and inflammatory markers were measured using biochemical kits and quantitative real‐time polymerase chain reaction. Serum fibroblast growth factor 19 (FGF19) was detected using an enzyme‐linked immunosorbent assay. The bile acid (BA) profiles in the liver, serum, and intestinal contents were determined using ultraperformance liquid chromatography coupled with mass spectrometry. The composition of intestinal bacteria was analyzed with 16S rRNA gene amplicon sequencing. Results: LP supplementation was associated with improved markers of liver disease, inflammation, and oxidative stress in PN‐fed piglets. Moreover, markers of intestinal injury and inflammation were alleviated by LP in PN‐fed piglets. Mechanistically, LP increased the abundance of Lactobacillus in ileal contents and stimulated FGF19 expression in ileal mucosa. Subsequently, it increased the expression of small heterodimer partner (SHP) and inhibited cholesterol 7α‐hydroxylase (CYP7A1) expression in the liver. Additionally, LP altered the systemic composition and metabolism of BAs. Conclusions: LP alleviated liver and intestinal injury in PN‐fed neonatal piglets by altering the composition of intestinal bacteria and BAs. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Upregulation of cadherin‐11 contributes to cholestatic liver fibrosis.
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Wu, Bo, Tian, Xinbei, Wang, Weipeng, Zhu, Jing, Lu, Ying, Du, Jun, and Xiao, Yongtao
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HEPATIC fibrosis ,BILIARY atresia ,BILE ducts ,LIVER cells ,LIVER histology - Abstract
Importance: Cadherin‐11 (CDH11), a cell‐to‐cell adhesion molecule, is implicated in the fibrotic process of several organs. Biliary atresia (BA) is a common cholestatic liver disease featuring cholestasis and progressive liver fibrosis in children. Cholestatic liver fibrosis may progress to liver cirrhosis and lacks effective therapeutic strategies. Currently, the role of CDH11 in cholestatic liver fibrosis remains unclear. Objective: This study aimed to explore the functions of CDH11 in cholestatic liver fibrosis. Methods: The expression of CDH11 in BA livers was evaluated by database analysis and immunostaining. Seven BA liver samples were used for immunostaining. The wild type (Wt) and CDH11 knockout (CDH11–/–) mice were subjected to bile duct ligation (BDL) to induce cholestatic liver fibrosis. The serum biochemical analysis, liver histology, and western blotting were used to assess the extent of liver injury and fibrosis as well as activation of transforming growth factor‐β (TGF‐β)/Smad pathway. The effect of CDH11 on the activation of hepatic stellate cell line LX‐2 cells was investigated. Results: Analysis of public RNA‐seq datasets showed that CDH11 expression levels were significantly increased in livers of BA, and CDH11 was correlated with liver fibrosis in BA. BDL‐induced liver injury and liver fibrosis were attenuated in CDH11–/– mice compared to Wt mice. The protein expression levels of phosphorylated Smad2/3 were decreased in livers of CDH11–/– BDL mice compared to Wt BDL mice. CDH11 knockdown inhibited the activation of LX‐2 cells. Interpretation: CDH11 plays an important role in cholestatic liver fibrosis and may represent a potential therapeutic target for cholestatic liver disease, such as BA. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Fish oil–based lipid emulsion alleviates parenteral nutrition–associated liver diseases and intestinal injury in piglets.
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Chen, Shanshan, Xiao, Yongtao, Liu, Yang, Tian, Xinbei, Wang, Weipeng, Jiang, Lu, Wu, Wenjie, Zhang, Tian, Cai, Wei, and Wang, Ying
- Subjects
BIOLOGICAL models ,BIOMARKERS ,LIPOPOLYSACCHARIDES ,GUT microbiome ,ANIMAL experimentation ,SWINE ,LIVER diseases ,TREATMENT effectiveness ,COMPARATIVE studies ,OXIDATIVE stress ,INTESTINAL diseases ,BILE acids ,PARENTERAL feeding ,INTRAVENOUS fat emulsions ,FISH oils - Abstract
Background: Thisstudy aimed to investigate the impact of fish oil–based lipid emulsion (FO) on enterohepatic injuries and intestinal microbiota in piglets of parenteral nutrition (PN). Methods: Newborn piglets were divided into three groups, including enteral diet (the controls), PN with 100% FO and PN with medium‐chain triglyceride/long‐chain triglyceride–based lipid emulsion (MCT/LCT) for 14 days. Serum biochemical indicators, hepatic and intestinal histology, and expression of genes associated with inflammation, oxidative stress, and lipid metabolism were measured. The bile acid (BA) profiles in serum and the taxonomic composition of the gut microbiome in different intestinal segments were analyzed. Results: Compared with MCT/LCT–piglets, FO reduced inflammation, promoted fatty acid oxidation, and decreased oxidative stress in the liver. In the intestine, FO decreased intestinal inflammation and intestinal permeability, leading to reduced lipopolysaccharide entry into the blood circulation relative to MCT/LCT–piglets. PN groups have dominant contents of Proteobacteria and Bacteroides, whereas the control group have Firmicutes at the phylum level. FO altered the taxonomic compositions of the gut microbiome in different segments, increased the relative abundance of Bacteroidaceae in ileum, and Rikenellaceae and Ruminococcaceae in the colon. FO treatment shifted BA composition ratio in serum and had a lower ratio of secondary BAs to primary BAs. Conclusion: FO alleviates PNLAD and intestinal injury by regulating the homeostasis of BAs' enterohepatic circulation and altering microbiota composition in different intestinal segments. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Loss function of Bcr mutation causes gastrointestinal dysmotility and brain developmental defects.
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Xiao, Yongtao, Sun, Yu, Lu, Ying, Du, Jun, Tian, Xinbei, Cai, Wei, and Wang, Ying
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GENETIC mutation , *SUBMUCOUS plexus , *RHO GTPases , *GASTROINTESTINAL motility , *CENTRAL nervous system - Abstract
Background: The breakpoint cluster region (BCR) is a protein that originally forms a fusion protein with c‐Abl tyrosine kinase and induces leukemia. Researchers have shown that BCR is enriched in the central nervous system and may contribute to neurological disorders. We aimed to investigate the physiological function of BCR in neural development in the gastrointestinal (GI) tract and brain. Methods: Whole‐exome sequencing was used to screen for mutations in the BCR. Bcr knockout mice (Bcr−/−, ΔExon 2–22) were generated using the CRISPR/Cas9 system. Transit of carmine red dye and glass bead expulsion assays were used to record total and proximal GI transit and distal colonic transit. Key Results: In an infant with pediatric intestinal pseudo‐obstruction, we found a heterozygous de novo mutation (NM_004327.3:c.3072+1G>A) in BCR. Bcr deficiency mice (Bcr−/−) exhibited growth retardation and impaired gastrointestinal motility. Bcr−/− mice had a prolonged average total GI transit time with increased distal colonic transit and proximal GI transit in isolation. Morphology analysis indicated that Bcr−/− mice had a less number of neurons in the submucosal plexus and myenteric plexus. Bcr−/− mice exhibited apparent structural defects in the brain, particularly in the cortex. Additionally, Bcr− depletion in the mouse cortex altered the expression of Ras homologous (Rho) family small GTPases. Conclusions and Inferences: BCR mutations are associated with intestinal obstruction in children. Loss of Bcr can cause intestinal dysmotility and brain developmental defects may via regulation of Rho GTPases. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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7. A nonbile acid farnesoid X receptor agonist tropifexor potently inhibits cholestatic liver injury and fibrosis by modulating the gut–liver axis.
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Xiao, Yongtao, Wang, Ying, Liu, Yang, Wang, Weipeng, Tian, Xinbei, Chen, Shanshan, Lu, Ying, Du, Jun, and Cai, Wei
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FARNESOID X receptor , *LIVER injuries , *FIBROBLAST growth factors , *BILIARY atresia , *NON-alcoholic fatty liver disease - Abstract
Background & Aims: Tropifexor (TXR) is a novel nonbile acid that acts as an agonist of farnesoid X receptor (FXR). TXR is currently in Phase 2 trials for the treatment of non‐alcoholic steatohepatitis (NASH). Herein, we report the impact of TXR on in a piglet model in which cholestatic liver damage and fibrosis where induced by bile duct ligation (BDL). Methods: The piglets received BDL and TXR for 2 wk. Hepatic, portal and colonic bile acid and amino acid profiles and gut microbiome were analysed. Portal fibroblast growth factor (FGF) 19 levels were measured using an enzyme‐linked immunosorbent assay (ELISA). Results: We first showed that bile acid metabolism and signalling are dysfunctional in patients with biliary atresia. Next, we observed that TXR potently suppresses BDL‐induced liver injury, fibrosis and ductular reaction in piglets. Within the ileum, TXR enhances FGF19 expression and subsequently increases portal FGF19 levels. In the liver, TXR promotes the expression of small heterodimer partner (SHP) and inhibits cholesterol 7α‐hydroxylase (CYP7A1). Additionally, TXR increases the abundance of bile acid‐biotransforming bacteria in the distal ileum and alters the composition of amino acids in the colon. Lastly, TXR ameliorates intestinal barrier injury in piglets subjected to BDL. Conclusion: TXR potently ameliorated cholestatic liver injury and fibrosis by modulating the gut–liver axis in piglets. It supports the clinical evaluation of TXR as a therapeutic strategy for cholestatic liver diseases, such as biliary atresia. [ABSTRACT FROM AUTHOR]
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- 2021
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8. The Farnesoid X Receptor Agonist Tropifexor Prevents Liver Damage in Parenteral Nutrition-fed Neonatal Piglets.
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Yang Liu, Yongtao Xiao, Shanshan Chen, Xinbei Tian, Weipeng Wang, Ying Wang, Wei Cai, Liu, Yang, Xiao, Yongtao, Chen, Shanshan, Tian, Xinbei, Wang, Weipeng, Wang, Ying, and Cai, Wei
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- 2021
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9. Congenital Short‐Bowel Syndrome: Clinical and Genetic Presentation in China.
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Wang, Ying, Chen, Shanshan, Yan, Weihui, Lu, Lina, Tao, Yijng, Xiao, Yongtao, and Cai, Wei
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CATHETER-related infections ,SHORT bowel syndrome ,PARENTERAL feeding ,INTESTINES ,CHINESE people ,MEMBRANE proteins ,PATIENTS' families - Abstract
Background: Congenital short‐bowel syndrome (CSBS) is a rare disorder characterized by retardation of intestinal development. However, it is still not well recognized at present. In this study, the etiological, clinical, and genetic characteristics of CSBS in China were analyzed. Methods: Nine infants with CSBS were recruited. Full‐thickness biopsy findings were evaluated by histopathology. Whole‐exome sequencing was performed to identify mutations in patients and their family members. All patients were followed up at >1 year of age. Results: Six of 9 infants had malrotation, and 2 patients had intestinal atresia. The average total small‐bowel length was 51.7 (40–75) cm. Coxsackie and adenovirus receptor‐like membrane protein (CLMP) mutations were found in 5 patients and were related to decreases in ileal goblet cells and mucous secretion. Among these 5 patients, 3 shared the same mutation (c. 206G>A p.R69H), 1 patient had an exon 3–5 deletion, and 1 patient had the C.655T>G, p.Cys219Gly, and C.389‐2A>C. Another case carried a loss‐of‐function mutation in filamin A (FLNA). In the other 3 patients, no pathogenic mutations in genes related to intestinal development were found. The rate of catheter‐related bloodstream infection was 4.3 per 1000 catheter days, and intestinal failure–associated liver disease (IFALD) was 77.8%. The median follow‐up duration was 24.1 months. Eight patients were weaned off parenteral nutrition (PN). Six patients still exhibited malnutrition during follow‐up. Conclusions: Infants with CSBS often need long‐term PN and remain at risk of SBS‐related complications. CLMP and FLNA mutations are associated with CSBS in the Chinese population. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Variants in the Enteric Smooth Muscle Actin γ-2 Cause Pediatric Intestinal Pseudo-obstruction in Chinese Patients.
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Wei, Zhiliang, Lu, Lina, Zheng, Youjie, Yan, Weihui, Tao, Yijng, Xiao, Yongtao, Cai, Wei, and Wang, Ying
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- 2021
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11. PI3K: A potential therapeutic target for cancer.
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Chen, Yingwei, Wang, Bao-Can, and Xiao, Yongtao
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CANCER treatment ,KINASES ,LIPIDS ,CELL proliferation ,CLINICAL trials ,DATA analysis - Abstract
Phosphatidylinositol 3-kinase (PI3K), one member of lipid kinase family, has been demonstrated to play a key role in regulating cell proliferation, adhesion, survival, and motility. Recent studies indicate that PI3K related signaling pathway is one of the most commonly activated pathways in human cancers. Accordingly, pharmacological inhibition of key nodes in this signaling cascade has been a focus in developmental therapeutics. To date, Inhibitors targeting PI3K or nodes in this pathway, AKT and mTOR, are best studied and have reached clinical trials. In this review, we will focus on recent progress on understanding of PI3Ks signaling pathway and the development of PI3K inhibitors. J. Cell. Physiol. 227: 2818-2821, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
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- 2012
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12. Krüppel-like factor 9 promotes neuroblastoma differentiation via targeting the sonic hedgehog signaling pathway.
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Chen, Sheng, Gu, Song, Xu, Min, Mei, Dongyu, Xiao, Yongtao, Chen, Kai, and Yan, Zhilong
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- 2020
- Full Text
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