27 results on '"Rui-Xu Yang"'
Search Results
2. Ammonia Scavenger Restores Liver and Muscle Injury in a Mouse Model of Non-alcoholic Steatohepatitis With Sarcopenic Obesity
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Zi-Xuan Wang, Meng-Yu Wang, Rui-Xu Yang, Ze-Hua Zhao, Feng-Zhi Xin, Yu Li, Tian-Yi Ren, and Jian-Gao Fan
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sarcopenia ,obesity ,ammonia ,L-ornithine L-aspartate ,steatohepatitis ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Recent studies have revealed that sarcopenia is closely associated with obesity and non-alcoholic steatohepatitis (NASH). However, few attempted to explore the cause-and-effect relationship between sarcopenic obesity and NASH. In this study, we investigated muscular alterations in a rodent NASH model to elucidate their intrinsic relations and explore the potential therapeutic target. Forty-six 8-week-old and twenty 42-week-old male C57BL/6 mice (defined as young and middle-aged mice, respectively) were fed with a high-fat diet (HFD) for 12 or 20 weeks. A subset of young mice was subjected to ammonia lowering treatment by L-ornithine L-aspartate (LOLA). We examined body composition and muscle strength by nuclear magnetic resonance and grip strength meter, respectively. At the end of the 12th week, all HFD-fed mice developed typical steatohepatitis. Meanwhile, sarcopenia occurred in HFD-fed middle-aged mice, whereas young mice only demonstrated decreased grip strength. Until the end of week 20, young mice in the HFD group exhibited significant sarcopenia and obesity phenotypes, including decreased lean body mass and grip strength, and increased body fat mass and percentage body fat. Additionally, plasma ammonia level was markedly increased in HFD-fed mice of both ages at week 20. Plasma ammonia level was negatively associated with muscle strength and myofiber diameter in young mice. LOLA can significantly reduce plasma levels of ammonia, alanine aminotransaminase, aspartate aminotransaminase, and cholesterol in mice fed an HFD. Hepatic infiltration of inflammatory cells and collagen deposition area were significantly decreased in HFD group by LOLA treatment. Meanwhile, LOLA significantly increased lean body mass, grip strength, and average muscle fiber diameter of HFD-fed mice. These findings suggest that the occurrence of NASH precedes sarcopenia in HFD mice, and the steatohepatitis-related hyperammonemia might contribute to the pathogenesis of sarcopenia. LOLA might be an effective drug for both steatohepatitis and sarcopenic obesity.
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- 2022
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3. Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis
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Rui-Xu Yang, Qin Pan, Xiao-Lin Liu, Da Zhou, Feng-Zhi Xin, Ze-Hua Zhao, Rui-Nan Zhang, Jing Zeng, Liang Qiao, Chun-Xiu Hu, Guo-Wang Xu, and Jian-Gao Fan
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Ceramides ,Autophagy ,High fat diet ,Non-alcoholic fatty liver disease ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Background Ceramide plays pathogenic roles in nonalcoholic fatty liver disease (NAFLD) via multiple mechanisms, and as such inhibition of ceramide de novo synthesis in the liver may be of therapeutically beneficial in patients with NAFLD. In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy. Methods Sprague Dawley rats were randomly divided into three groups: standard chow (n = 10), high-fat diet (HFD) (n = 10) or HFD combined with oral administration of myriocin (0.3 mg/kg on alternate days for 8 weeks) (n = 10). Liver histology and autophagy function were measured. HepG2 cells were incubated with fatty acid with or without myriocin treatment. Lipid accumulation and autophagy markers in the HepG2 cells were analyzed. Serum ceramide changes were studied in 104 subjects consisting healthy adults, liver biopsy-proven patients with NAFLD and liver biopsy-proven patients with chronic hepatitis B (CHB). Results Myriocin reversed the elevated body weight and serum transaminases and alleviated dyslipidemia in HFD fed rats. Myriocin treatment significantly attenuated liver pathology including steatosis, lobular inflammation and ballooning. By qPCR analysis, it was revealed that myriocin corrected the expression pattern of fatty acid metabolism associated genes including Fabp1, Pparα, Cpt-1α and Acox-2. Further, myriocin also restored the impaired hepatic autophagy function in rats with HFD-induced NASH, and this has been verified in HepG2 cells. Among the sphingolipid species that we screened in lipidomic profiles, significantly increased ceramide was observed in NASH patients as compared to the controls and non-NASH patients, regardless of whether or not they have active CHB. Conclusions Ceramide may play an important regulatory role in the autophagy function in the pathogenesis of NASH. Hence, blockade of ceramide signaling by myriocin may be of therapeutically beneficial in NASH. Trial registration Registration ID: ChiCTR-DDT-13003983. Data of registration: 13 May, 2013, retrospectively registered.
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- 2019
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4. Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression
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Da Zhou, Yuan-Wen Chen, Ze-Hua Zhao, Rui-Xu Yang, Feng-Zhi Xin, Xiao-Lin Liu, Qin Pan, Huiping Zhou, and Jian-Gao Fan
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Medicine ,Biochemistry ,QD415-436 - Abstract
Fatty liver disease: A gutsy way to prevent disease progression A treatment for non-alcoholic fatty liver disease that incorporates a metabolite found in the gut could prevent progression to a more serious liver condition. Drugs that enhance the activity of glucagon-like peptide-1 (GLP-1), a protein involved in regulating metabolic processes, have shown promise in targeting non-alcoholic fatty liver disease and the more serious condition, steatohepatitis. However, some patients appear resistant to treatment. Jian-Gao Fan at Shanghai Jiao Tong University in China, Huiping Zhou at McGuire VA Medical Center in Richmond, USA, and co-workers demonstrated that a gut metabolite called sodium butyrate may help encourage responsiveness to GLP-1 treatment. The team found that liver GLP-1R expression was considerably reduced in patients with liver disease compared with healthy controls. Experiments on mouse models showed that treatment incorporating sodium butyrate improved GLP-1R levels and reduced fatty liver deposits.
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- 2018
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5. Transcriptomic Landscape Analysis Reveals a Persistent DNA Damage Response in Metabolic Dysfunction-associated Steatohepatitis Post-dietary Intervention.
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Zi-Yuan Zou, Tian-Yi Ren, Jia-Qi Li, Ting-Ying Jiao, Meng-Yu Wang, Lei-Jie Huang, Shuang-Zhe Lin, Yuan-Yang Wang, Xiao-Zhen Guo, Ye-Yu Song, Rui-Xu Yang, Cen Xie, and Jian-Gao Fan
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- 2024
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6. Chest Circumference Predicts MAFLD Better than Waist Circumference and BMI in Obese Prepubertal Children Aged 8 Years
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Jing Zeng, Qian Jin, Jing Yang, Rui-Xu Yang, Rui-Nan Zhang, Jian Zhao, and Jian-Gao Fan
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Backgroundand Aim Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the entire spectrum of liver diseases associated with metabolic disorders. This study aimed to determine the prevalence of MAFLD using controlled attenuation parameter (CAP) values obtained by transient elastography (TE) technique and identify the optimal predicator for diagnosing MAFLD in this population. Methods This study enrolled children who were part of the Shanghai Birth Cohort Study and had completed the 8-year-old follow-up. Anthropometric measurements were taken, and FibroScan-502 examination with an M probe (Echosens, Paris, France) was conducted on these children. The diagnosis of MAFLD was based on the median CAP exceeding 248 dB/m and predefined criteria. Receiver operating characteristic (ROC) curve analysis was performed to identify the optimal predicator for MAFLD in these children. Results A total of 848 healthy 8-year-old children (431 boys and 417 girls) who participated in the Shanghai Birth Cohort Study were included in the analysis. Among them, 113 (13.33%) children were classified as obese. The prevalence of obesity was significantly higher in boys (17.63%) than in girls (8.87%) (p < 0.001). The prevalence of central obesity was significantly higher in girls (34.05%) than in boys (22.04%) (p < 0.001). MAFLD was diagnosed in 29 (3.42%) children. The prevalence of MAFLD was significantly higher in the obese group (15.93%) than in the non-obese group (1.50%) (p < 0.05). Children with MAFLD had significantly higher weight, BMI, chest circumference, waist circumference, hip circumference, waist-to-height ratio, waist-to-hip ratio, and liver stiffness measurement than non-MAFLD (all p < 0.05). Waist circumference (OR: 1.187; 95%CI: 1.132-1.243; p < 0.001) was significantly associated with the presence of MAFLD in these participants in multivariate linear regression analyses. Chest circumference (OR: 1.321; 95%CI: 1.123-1.424; p < 0.001) was significantly associated with the presence of MAFLD in obese participants and had the largest AUC of 0.813 in ROC curve analysis. Conclusion This study highlights the prevalence of MAFLD in prepubertal children, particularly in the obese subgroup. Our findings also suggest that chest circumference is an optimal anthropometric predicator for MAFLD in 8-year-old obese children.
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- 2023
7. The burden and sexual dimorphism with nonalcoholic fatty liver disease in Asian children: A systematic review and meta‐analysis
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Jing Zeng, Tian-Yi Ren, Jian-Gao Fan, Rui-Xu Yang, Lei-Jie Huang, Qian-Ren Zhang, Zi-Yuan Zou, Meng-Yu Wang, and Yi-Wen Shi
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Adult ,Male ,Pediatric Obesity ,medicine.medical_specialty ,Prevalence ,Overweight ,Body Mass Index ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Child ,Sex Characteristics ,Hepatology ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,digestive system diseases ,Sexual dimorphism ,Meta-analysis ,Female ,medicine.symptom ,business ,Body mass index - Abstract
BACKGROUND Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized. METHODS We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses and meta-regression were all performed. RESULTS Thirty-three study populations were finally included. Nine of them comprising 20 595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004 to 2010 to the last decade. Male predominant trends were observed in paediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after 10 years of age, boys were more prone to have NAFLD than girls (OR = 1.75; P = .0012). In addition, the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n = 2610), overweight (16.72%, 95% CI 7.07%-34.65%, n = 1265) and obese children (50.13%, 95% CI 41.99%-58.27%, n = 6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (P = .0396) and body mass index (P
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- 2021
8. The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease: A multicenter cross-sectional study in China
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Yuqiang Mi, Junping Shi, Rui-Xu Yang, Jia Shang, Branko Popovic, Qin Du, Hong Deng, Fang-Ping He, Jian-Gao Fan, Fu-Sheng Di, Yong-Jian Zhou, Jinjun Chen, Caiyan Zhao, Rui-Dan Zheng, Zheng-Sheng Zou, and Bi-Hui Zhong
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Liver Cirrhosis ,China ,medicine.medical_specialty ,Cirrhosis ,Biopsy ,Gastroenterology ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Diabetes mellitus ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Metabolic Syndrome ,Hepatology ,medicine.diagnostic_test ,business.industry ,Fatty liver ,nutritional and metabolic diseases ,medicine.disease ,Comorbidity ,Cross-Sectional Studies ,Liver biopsy ,Insulin Resistance ,Metabolic syndrome ,business - Abstract
Background This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). Methods This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. Results Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037–8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388–4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772–9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398–6.210; P = 0.004) after the adjustments of the BMI and diabetes. Conclusions Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.
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- 2021
9. Epidemiological trends and clinical characteristic of NAFLD/MAFLD in Asia
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Rui Xue, Rui Xu Yang, and Jian Gao Fan
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Metabolic Syndrome ,Asia ,Non-alcoholic Fatty Liver Disease ,Gastroenterology ,Humans ,Obesity - Published
- 2022
10. Metabolic Disorders Combined with Noninvasive Tests to Screen Advanced Fibrosis in Nonalcoholic Fatty Liver Disease
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Jian-Gao Fan, Zheng-Sheng Zou, Hong Deng, Junping Shi, Bi-Hui Zhong, Jinjun Chen, Yong-Jian Zhou, Qin Du, Caiyan Zhao, Jia Shang, Rui-Xu Yang, Yi-Wen Shi, Branko Popovic, Yuqiang Mi, Rui-Dan Zheng, Fang-Ping He, and Fu-Sheng Di
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medicine.medical_specialty ,Hepatology ,business.industry ,Liver fibrosis ,nutritional and metabolic diseases ,medicine.disease ,digestive system ,Gastroenterology ,Metabolic syndrome ,digestive system diseases ,Advanced fibrosis ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Noninvasive measurement ,Original Article ,business - Abstract
Background and Aims Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic disorders. This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients. Methods A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers. We compared the severity of fibrosis in patients with different components of metabolic disorders. Based on standard noninvasive tests and metabolic disorders, we developed new algorithms to identify advanced fibrosis. Results Metabolic syndrome (MetS) was frequent in NAFLD patients (133/246, 54%). Patients with MetS had a higher proportion of significant fibrosis (p=0.014) and higher LSM values (9.2 kPa, vs. 7.4 kPa, p=0.002) than those without MetS. Patients with more metabolic disorders had higher fibrosis stages (p=0.017). Reduced high-density lipoprotein cholesterol (odds ratio [OR]: 2.241, 95% confidence interval [CI]: 1.004–5.002, p=0.049) and raised fasting glucose (OR: 4.500, 95% CI: 2.083–9.725, p
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- 2021
11. Global multi-stakeholder endorsement of the MAFLD definition
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Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam, Maria Lorena Abate, Bahaa Abbas, Ahmed Amr Abbassy, Waleed Abd El Ghany, Amira Abd Elkhalek, Emad Abd ElMajeed, Mohammad Abdalgaber, Mohamed AbdAllah, Marwa Abdallah, Nourhan Abdallah, Shereen Abdelaleem, Yasser Abdelghani, Wael Abdelghany, Safaa Mohamed Abdelhalim, Wafaa Abdelhamid, Nehal Abdelhamid, Nadia A. Abdelkader, Elsayed Abdelkreem, Aly Mohamed Abdelmohsen, Awny Ali Abdelrahman, Sherief M Abd-elsalam, Doaa Abdeltawab, Abdulbaset Abduh, Nada Abdulhakam, Maheeba Abdulla, Navid Abedpoor, Ludovico Abenavoli, Fredrik Åberg, Omala Ablack, Mostafa Abo elftouh, Yousry Esam-Eldin Abo-Amer, Ashraf Aboubkr, Alaa Aboud, Amr M. Abouelnaga, Galal A. Aboufarrag, Ashraf Aboutaleb, Leticia Abundis, Gupse Adalı, Enrique Adames, Leon Adams, Danjuma Adda, Noor Adel, Nada Adel, Muhammad Adel Sayed, Taiba Jibril Afaa, Nawal Afredj, Gulnara Aghayeva, Alessio Aghemo, Carlos A. Aguilar-Salinas, Golo Ahlenstiel, Walid Ahmady, Wafaa Ahmed, Amira Ahmed, Samah Nasser Ahmed, Heba Mostafa Ahmed, Rasha Ahmed, Elmar Aigner, Mesut Akarsu, Maisam Akroush, Umit Akyuz, Mamun Al Mahtab, Tahani Al Qadiri, Yusriya Al Rawahi, Razzaq AL rubaee, Muna Al Saffar, Shahinul Alam, Zaid Al-Ani, Agustín Albillos, Mohamed Alboraie, Said Al-Busafi, Mohamed Al-Emam, Jawaher Alharthi, Kareem Ali, Basma Abdelmoez Ali, Mohammad Ali, Raja Affendi Raja Ali, Anna Alisi, Ali Raad AL-Khafaji, Maryam Alkhatry, Rocio Aller, Yahya Almansoury, Khalid Al-Naamani, Alaa Alnakeeb, Anna Alonso, Saleh A. Alqahtani, Leina Alrabadi, Khalid Alswat, Mahir Altaher, Turki Altamimi, Jose Altamirano, Mario R. Alvares-da-Silva, Elsragy Adel M. Aly, Amgad Alzahaby, Ahmed Alzamzamy, Keisuke Amano, Maysa A. Amer, Mona A. Amin, Sayed A. Amin, Ashraf A. Amir, Javier Ampuero, Noha Anas, Pietro Andreone, Soa Fy Andriamandimby, Mahmoud Anees, Peltec Angela, Manal Antonios, Wael Arafat, Jose Moreno Araya, Juan Armendariz-Borunda, Matthew J. Armstrong, Hassan Ashktorab, Patricia Aspichueta, Fathia Assal, Mira Atef, Dina Attia, Hoda Atwa, Reham Awad, Mohyeldeen Abd Elaziz Awad, Sally Awny, Obafemi Awolowo, Yaw Asante Awuku, Ibrahim Ayada, Than Than Aye, Sherif Ayman, Hedy Ayman, Hesham Ayoub, Hosny M. Azmy, Romiro P. Babaran, Omneya Badreldin, Ahmed Badry, İbrahim Halil Bahçecioğlu, Amira Bahour, Jiajia Bai, Yasemin Balaban, Muthuswamy Balasubramanyam, Khaled Bamakhrama, Jesus M Banales, Babu Bangaru, Jianfeng Bao, Jorge Suazo Barahona, Salma Barakat, Sandra Maria Barbalho, Bikwa Barbra, Beatriz Barranco, Francisco Barrera, Ulrich Baumann, Shamardan Bazeed, Eva Bech, Aourarh Benayad, Andreas Benesic, David Bernstein, Fernando Bessone, Susie Birney, Cyrille Bisseye, Martin Blake, Bilal Bobat, Leonilde Bonfrate, Dmitry S Bordin, Francisco Bosques-Padilla, Jerome Boursier, Boushab Mohamed Boushab, David Bowen, Patricia Medina Bravo, Paul N Brennan, Bisi Bright, Ilse Broekaert, Xabier Buque, Diego Burgos-Santamaría, Julio Burman, Luca Busetto, Chris D. Byrne, Patricia Anne I. Cabral-Prodigalidad, Guillermo Cabrera-Alvarez, Wei Cai, Francesca Cainelli, Ali Riza Caliskan, Ali Canbay, Ana Cano-Contreras, Hai-Xia Cao, Zhujun Cao, Andres Carrion, Francesca Carubbi, Teresa Casanovas, Marlen Ivón Castellanos Fernández, Jin Chai, Siew Pheng Chan, Phunchai Charatcharoenwitthaya, Norberto Chavez-Tapia, Kazuaki Chayama, Jinjun Chen, Lin Chen, Zhong-Wei Chen, Huiting Chen, Sui-Dan Chen, Qiang Chen, Yaxi Chen, Gang Chen, En-Quang Chen, Fei Chen, Pei-Jer Chen, Robert Cheng, Wendy Cheng, Jack Tan Wei Chieh, Imad Chokr, Evangelos Cholongitas, Ashok Choudhury, Abhijit Chowdhury, Evaristus Sunday Chukwudike, Stefano Ciardullo, Michelle Clayton, Karine Clement, Marie Michelle Cloa, Cecilia Coccia, Cristina Collazos, Massimo Colombo, Arif Mansur Cosar, Helma Pinchemel Cotrim, Joris Couillerot, Alioune Coulibaly, Gonzalo Crespo, Javier Crespo, Maria Cruells, Ian Homer Y. Cua, Hesham K. Dabbous, George N Dalekos, Patricia D'Alia, Li Dan, Viet Hang Dao, Mostafa Darwish, Christian Datz, Milagros B Davalos-Moscol, Heba Dawoud, Blanca Olaechea de Careaga, Robert de Knegt, Victor de Ledinghen, Janaka de Silva, Nabil Debzi, Marie Decraecker, Elvira Del Pozo, Teresa C Delgado, Manuel Delgado-Blanco, Łukasz Dembiński, Adilson Depina, Moutaz Derbala, Hailemichael Desalegn, Christèle Desbois-Mouthon, Mahmoud Desoky, Anouk Dev, Agostino Di Ciaula, Moisés Diago, Ibrahima Diallo, Luis Antonio Díaz, Melisa Dirchwolf, Paola Dongiovanni, Andrriy Dorofeyev, Xiaoguang Dou, Mark W. Douglas, Michael Doulberis, Cecil K. Dovia, Adam Doyle, Ivana Dragojević, Joost PH Drenth, Xuefei Duan, Audrius Dulskas, Dan L Dumitrascu, Oliver Duncan, Vincent Dusabejambo, Rev. Shem N.A. Dwawhi, Sho Eiketsu, Doaa El Amrousy, Ahmed El Deeb, Ghada El Deriny, Hesham Salah El Din, Salwa El Kamshishy, Mohamed El Kassas, Maissa El Raziky, Osama A Elagamy, Wafaa Elakel, Dina Elalfy, Hanaa Elaraby, Heba ElAwady, Reda Elbadawy, Hanaa Hassan Eldash, Manal S. Eldefrawy, Carol Lezama Elecharri, Amel Elfaramawy, Mohammed Elfatih, Mahmoud Elfiky, Mohamed Elgamsy, Mohamed Elgendy, Mohamed A. El-Guindi, Nagi Elhussieny, Ahmed Maher Eliwa, Zeineb Elkabbany, Hesham El-Khayat, Nehal M. El-Koofy, Alaa Elmetwalli, Amr Elrabat, Fathiya El-Raey, Fatma Elrashdy, Medhat Elsahhar, Esraa M. Elsaid, Shimaa Elsayed, Hany Elsayed, Aly Elsayed, Amr M. Elsayed, Hamdy Elsayed, Magdy El-Serafy, Ahmed M. Elsharkawy, Reem Yehia Elsheemy, Eman Elsayed Elshemy, Sara Elsherbini, Naglaa Eltoukhy, Reda Elwakil, Ola Emad, Shaimaa Emad, Mohamed Embabi, Ilkay Ergenç, Tatiana Ermolova, Gamal Esmat, Doaa M. Esmat, Enrique Carrera Estupiñan, Said Ettair, Tcaciuc Eugen, Mohammed Ezz-Eldin, Lidia Patricia Valdivieso Falcón, Yu-Chen Fan, Samah Fandari, Mahmoud Farag, Taghreed Mohamed Farahat, Eman M. Fares, Michael Fares, Eduardo Fassio, Hayam Fathy, Dina Fathy, Wael Fathy, Soheir Fayed, Dan Feng, Gong Feng, Miguel Fernández-Bermejo, Cristina Targa Ferreira, Javier Díaz Ferrer, Alastair Forbes, Rabab Fouad, Hanan M. Fouad, Tove Frisch, Hideki Fujii, Shuhei Fukunaga, Shinya Fukunishi, Hacer Fulya, Masato Furuhashi, Yasmine Gaber, Augusto Jose G. Galang, Jacqueline Cordova Gallardo, Rocío Galloso, Mahmoud Gamal, Reham Gamal, Hadeel Gamal, Jian Gan, Anar Ganbold, Xin Gao, George Garas, Tony Garba, Miren García-Cortes, Carmelo García-Monzón, Javier García-Samaniego, Amalia Gastaldelli, Manuel Gatica, Elizabeth Gatley, Tamar Gegeshidze, Bin Geng, Hasmik Ghazinyan, Salma Ghoneem, Luca Giacomelli, Gianluigi Giannelli, Edoardo G. Giannini, Matthew Giefer, Pere Ginès, Marcos Girala, Pablo J Giraudi, George Boon-Bee Goh, Ahmed Ali Gomaa, Benbingdi Gong, Dina Hilda C. Gonzales, Humberto C. Gonzalez, Maria Saraí Gonzalez-Huezo, Isabel Graupera, Ivica Grgurevic, Henning Grønbæk, Xuelian Gu, Lin Guan, Ibrahima Gueye, Alice Nanelin Guingané, Ozen Oz Gul, Cuma Bulent Gul, Qing Guo, Pramendra Prasad Gupta, Ahmet Gurakar, Juan Carlos Restrepo Gutierrez, Ghada Habib, Azaa Hafez, Emilia Hagman, Eman Halawa, Osama Hamdy, Abd Elkhalek Hamed, Dina H. Hamed, Saeed Hamid, Waseem Hamoudi, Yu Han, James Haridy, Hanan Haridy, David C H Harris Harris, Michael Hart, Fuad Hasan, Almoutaz Hashim, Israa Hassan, Ayman Hassan, Essam Ali Hassan, Adel Ahmed Hassan, Magda Shehata Hassan, Fetouh Hassanin, Alshymaa Hassnine, John Willy Haukeland, Amr Ismael M. Hawal, Jinfan He, Qiong He, Yong He, Fang-Ping He, Mona Hegazy, Adham Hegazy, Osama Henegil, Nelia Hernández, Manuel Hernández-Guerra, Fatima Higuera-de-la-Tijera, Ibrahim Hindy, Keisuke Hirota, Lee Chi Ho, Alexander Hodge, Mohamed Hosny, Xin Hou, Jiao-Feng Huang, Yan Huang, Zhifeng Huang, Yuan Huang, Ang Huang, Xiao-Ping Huang, Sheng Hui-ping, Bela Hunyady, Mennatallah A. Hussein, Osama Hussein, Shahinaz Mahmoud Hussien, Luis Ibáñez-Samaniego, Jamal Ibdah, Luqman Ibrahim, Miada Ibrahim, Ibrahim Ibrahim, Maria E. Icaza-Chávez, Sahar Idelbi, Ramazan Idilman Idilman, Mayumi Ikeda, Giuseppe Indolfi, Federica Invernizzi, Iram Irshad, Hasan Mohamed Ali Isa, Natacha Jreige Iskandar, Abdulrahman Ismaiel, Mariam Ismail, Zulkifli Ismail, Faisal Ismail, Hideki Iwamoto, Kathryn Jack, Rachael Jacob, Fuad Jafarov, Wasim Jafri, Helen Jahshan, Prasun K Jalal, Ligita Jancoriene, Martin Janicko, Hiruni Jayasena, Meryem Jefferies, Vivekanand Jha, Fanpu Ji, Yaqiu Ji, Jidong Jia, Changtao Jiang, Ni Jiang, Zong-zhe Jiang, Xing Jin, Yi Jin, Xu Jing, Qian Jingyu, Maia Jinjolava, FX Himawan Haryanto Jong, Alina Jucov, Ibecheole Julius, Mona Kaddah, Yoshihiro Kamada, Abobakr kamal, Enas Mohamed Kamal, Ashraf Sayed Kamel, Jia-Horng Kao, Maja Karin, Thomas Karlas, Mohammad Kashwaa, Leolin Katsidzira, Eda Kaya, M.Azzam Kayasseh, Bernadette Keenan, Caglayan Keklikkiran, William Keml, Deia K. Khalaf, Rofida Khalefa, Sherin Khamis, Doaa Khater, Hamed khattab, Anatoly Khavkin, Olga Khlynova, Nabil Khmis, Nazarii Kobyliak, Apostolos Koffas, Kazuhiko Koike, Kenneth Y.Y. Kok, Tomas Koller, Narcisse Patrice Komas, Nataliya V. Korochanskaya, Yannoula Koulla, Shunji Koya, Colleen Kraft, Bledar Kraja, Marcin Krawczyk, Mohammad Shafi Kuchay, Anand V Kulkarni, Ashish Kumar, Manoj Kumar, Sulaiman Lakoh, Philip Lam, Ling Lan, Naomi F. Lange, Kamran Bagheri Lankarani, Nicolas Lanthier, Kateryna Lapshyna, Sameh A. Lashen, Konang Nguieguia Justine Laure, Leonid Lazebnik, Didier Lebrec, Samuel S. 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Soares Martins, Rana Marwan, Karen Frances Mason, Ghadeer Masoud, Mohamed Naguib Massoud, Maria Amalia Matamoros, Rosa Martín Mateos, Asmaa Mawed, Jean Claude Mbanya, Charles Mbendi, Lone McColaugh, Duncan McLeod, Juan Francisco Rivera Medina, Ahmed Megahed, Mai Mehrez, Iqbal Memon, Shahin Merat, Randy Mercado, Ahmed Mesbah, Taoufik Meskini, Mayada Metwally, Rasha Metwaly, Lei Miao, Eileen Micah, Luca Miele, Vladimir Milivojevic, Tamara Milovanovic, Yvonne L. Mina, Milan Mishkovik, Amal Mishriki, Tim Mitchell, Alshaimaa Mohamed, Mona Mohamed, Sofain Mohamed, Shady Mohammed, Ahmed Mohammed, Viswanathan Mohan, Sara Mohie, Aalaa Mokhtar, Reham Moniem, Mabel Segura Montilla, Jose Antonio Orozco Morales, María María Sánchez Morata, Jose Maria Moreno-Planas, Silvia Morise, Sherif Mosaad, Mohamed Moselhy, Alaa Mohamed Mostafa, Ebraheem Mostafa, Nezha Mouane, Nasser Mousa, Hamdy Mahfouz Moustafa, Abeer Msherif, Kate Muller, Christopher Munoz, Ana Beatriz Muñoz-Urribarri, Omar Alfaro Murillo, Feisul Idzwan Mustapha, Emir Muzurović, Yehia Nabil, Shaymaa Nafady, Ayu Nagamatsu, Atsushi Nakajima, Dan Nakano, Yuemin Nan, Fabio Nascimbeni, Mirella S. Naseef, Nagwa Nashat, Taran Natalia, Francesco Negro, Alexander V. Nersesov, Manuela Neuman, Masolwa Ng'wanasayi, Yan Ni, Amanda Nicoll, Takashi Niizeki, Dafina Nikolova, Wang Ningning, Madunil Niriella, K.A Nogoibaeva, Rozeena Nordien, Catherine O Sullivan, James O'Beirne, Solomon Obekpa, Ponsiano Ocama, Missiani Ochwoto, Michael Promise Ogolodom, Olusegun Ojo, Nana Okrostsvaridze, Claudia P. Oliveira, Raul Contreras Omaña, Omneya M. Omar, Hanaa Omar, Mabroka Omar, Salma Omran, Reham Omran, Marian Muse Osman, Nevin Owise, Theobald Owusu-Ansah, P. Martín Padilla- Machaca, Sirish Palle, Ziyan Pan, Xiao-Yan Pan, Qiuwei Pan, Apostolis Papaefthymiou, Feliciano Chanana Paquissi, Gabriella Par, Arit Parkash, Diana Payawal, Kevork M. 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R, Mandato, C, Mangia, A, Mann, J, Mansour, H, Mansouri, A, Mantovani, A, Mao, J, Maramag, F, Marchesini, G, Marcus, C, Marinho, R, Martinez-Chantar, M, Martins, A, Marwan, R, Mason, K, Masoud, G, Massoud, M, Matamoros, M, Mateos, R, Mawed, A, Mbanya, J, Mbendi, C, Mccolaugh, L, Mcleod, D, Medina, J, Megahed, A, Mehrez, M, Memon, I, Merat, S, Mercado, R, Mesbah, A, Meskini, T, Metwally, M, Metwaly, R, Miao, L, Micah, E, Miele, L, Milivojevic, V, Milovanovic, T, Mina, Y, Mishkovik, M, Mishriki, A, Mitchell, T, Mohamed, A, Mohamed, M, Mohamed, S, Mohammed, S, Mohammed, A, Mohan, V, Mohie, S, Mokhtar, A, Moniem, R, Montilla, M, Morales, J, Morata, M, Moreno-Planas, J, Morise, S, Mosaad, S, Moselhy, M, Mostafa, A, Mostafa, E, Mouane, N, Mousa, N, Moustafa, H, Msherif, A, Muller, K, Munoz, C, Munoz-Urribarri, A, Murillo, O, Mustapha, F, Muzurovic, E, Nabil, Y, Nafady, S, Nagamatsu, A, Nakajima, A, Nakano, D, Nan, Y, Nascimbeni, F, Naseef, M, Nashat, N, Natalia, T, Negro, F, Nersesov, A, Neuman, M, Ng'Wanasayi, M, Ni, Y, Nicoll, A, Niizeki, T, Nikolova, D, Ningning, W, Niriella, M, Nogoibaeva, K, Nordien, R, O Sullivan, C, O'Beirne, J, Obekpa, S, Ocama, P, Ochwoto, M, Ogolodom, M, Ojo, O, Okrostsvaridze, N, Oliveira, C, Omana, R, Omar, O, Omar, H, Omar, M, Omran, S, Omran, R, Osman, M, Owise, N, Owusu-Ansah, T, Padilla- Machaca, P, Palle, S, Pan, Z, Pan, X, Pan, Q, Papaefthymiou, A, Paquissi, F, Par, G, Parkash, A, Payawal, D, Peltekian, K, Peng, X, Peng, L, Peng, Y, Pengoria, R, Perez, M, Perez, J, Perez, N, Persico, M, Pessoa, M, Petta, S, Philip, M, Plaz Torres, M, Polavarapu, N, Poniachik, J, Portincasa, P, Pu, C, Purnak, T, Purwanto, E, Qi, X, Qian, Z, Qiang, Z, Qiao, Z, Qiao, L, Queiroz, A, Rabiee, A, Radwan, M, Rahetilahy, A, Ramadan, Y, Ramadan, D, Ramli, A, Ramm, G, Ran, A, Rankovic, I, Rao, H, Raouf, S, Ray, S, Reau, N, Refaat, A, Reiberger, T, Remes-Troche, J, Reyes, E, Richardson, B, Ridruejo, E, Riestra Jimenez, S, Rizk, I, Roberts, S, Roblero, J, Robles, J, Rockey, D, Rodriguez, M, Rodriguez Hernandez, H, Roman, E, Romeiro, F, Romeo, S, Rosales-Zabal, J, Roshdi, G, Rosso, N, Ruf, A, Ruiz, P, Runes, N, Ruzzenente, A, Ryan, M, Saad, A, Sabbagh, E, Sabbah, M, Saber, S, Sabrey, R, Sabry, R, Saeed, M, Said, D, Said, E, Sakr, M, Salah, Y, Salama, R, Salama, A, Saleh, H, Saleh, A, Salem, A, Salifou, A, Salih, A, Salman, A, Samouda, H, Sanai, F, Sanchez-Avila, J, Sanker, L, Sano, T, Sanz, M, Saparbu, T, Sawhney, R, Sayed, F, Sayed, S, Sayed, A, Sayed, M, Sebastiani, G, Secadas, L, Sediqi, K, Seif, S, Semida, N, Senates, E, Serban, E, Serfaty, L, Seto, W, Sghaier, I, Sha, M, Shabaan, H, Shalaby, L, Shaltout, I, Sharara, A, Sharma, V, Shawa, I, Shawkat, A, Shawky, N, Shehata, O, Sheils, S, Shewaye, A, Shi, G, Shi, J, Shimose, S, Shirono, T, Shou, L, Shrestha, A, Shui, G, Sievert, W, Sigurdardottir, S, Sira, M, Siradj, R, Sison, C, Smyth, L, Soliman, R, Sollano, J, Sombie, R, Sonderup, M, Sood, S, Soriano, G, Stedman, C, Stefanyuk, O, Stimac, D, Strasser, S, Strnad, P, Stuart, K, Su, W, Su, M, Sumida, Y, Sumie, S, Sun, D, Sun, J, Suzuki, H, Svegliati-Baroni, G, Swar, M, Taharboucht, S, Taher, Z, Takamura, S, Tan, L, Tan, S, Tanwandee, T, Tarek, S, Tatiana, G, Tavaglione, F, Tecson, G, Tee, H, Teschke, R, Tharwat, M, Thong, V, Thursz, M, Tine, T, Tiribelli, C, Tolmane, I, Tong, J, Tongo, M, Torkie, M, Torre, A, Torres, E, Trajkovska, M, Treeprasertsuk, S, Tsutsumi, T, Tu, T, Tur, J, Turan, D, Turcan, S, Turkina, S, Tutar, E, Tzeuton, C, Ugiagbe, R, Uygun, A, Vacca, M, Vajro, P, Van der Poorten, D, Van Kleef, L, Vashakidze, E, Velazquez, C, Velazquez, M, Vento, S, Verhoeven, V, Vespasiani-Gentilucci, U, Vethakkan, S, Vilaseca, J, Vitek, L, Volkanovska, A, Wallace, M, Wan, W, Wang, Y, Wang, X, Wang, C, Wang, M, Wangchuk, P, Weltman, M, White, M, Wiegand, J, Wifi, M, Wigg, A, Wilhelmi, M, William, R, Wittenburg, H, Wu, S, Wubeneh, A, Xia, H, Xiao, J, Xiao, X, Xiaofeng, W, Xiong, W, Xu, L, Xu, J, Xu, W, Xu, K, Xu, Y, Xu, S, Xu, M, Xu, A, Xu, C, Yan, H, Yang, J, Yang, R, Yang, Y, Yang, Q, Yang, N, Yao, J, Yara, J, Yaras, S, Yilmaz, N, Younes, R, Younes, H, Young, S, Youssef, F, Yu, Y, Yu, M, Yuan, J, Yue, Z, Yuen, M, Yun, W, Yurukova, N, Zakaria, S, Zaky, S, Zaldastanishvili, M, Zapata, R, Zare, N, Zerem, E, Zeriban, N, Zeshuai, X, Zhang, H, Zhang, X, Zhang, Y, Zhang, W, Zhang, Z, Zhao, J, Zhao, R, Zhao, H, Zheng, C, Zheng, Y, Zheng, R, Zheng, T, Zheng, K, Zhou, X, Zhou, Y, Zhou, H, Zhou, L, Zhu, L, Zhu, Y, Zhu, P, Ziada, E, Ziring, D, Ziyi, L, Zou, S, Zou, Z, Zou, H, Zuart Ruiz, R, and Global Multi-Stakeholder Consensus on the Redefinition of Fatty Liver Disease
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Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,Hepatology ,Non-alcoholic Fatty Liver Disease ,NAFLD ,consensu ,Gastroenterology ,MAFLD ,definition ,Humans ,MAFLD, NAFLD ,Human medicine - Abstract
Contains fulltext : 252162.pdf (Publisher’s version ) (Closed access)
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- 2022
12. Lipotoxic Hepatocyte‐Derived Exosomal MicroRNA 192‐5p Activates Macrophages Through Rictor/Akt/Forkhead Box Transcription Factor O1 Signaling in Nonalcoholic Fatty Liver Disease
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Qin Pan, Xiao-Lin Liu, Hai-Xia Cao, Feng-Zhi Xin, Huiping Zhou, Ze-Hua Zhao, Rui-Xu Yang, Jian-Gao Fan, and Jing Zeng
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Male ,0301 basic medicine ,Macrophage polarization ,FOXO1 ,Exosomes ,Proinflammatory cytokine ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Nonalcoholic fatty liver disease ,medicine ,Animals ,Interleukin 6 ,Protein kinase B ,Hepatology ,biology ,Chemistry ,Forkhead Transcription Factors ,Macrophage Activation ,medicine.disease ,Rats ,MicroRNAs ,Rapamycin-Insensitive Companion of mTOR Protein ,030104 developmental biology ,Integrin alpha M ,Hepatocytes ,Cancer research ,biology.protein ,030211 gastroenterology & hepatology ,Tumor necrosis factor alpha ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Background and aims Hepatic macrophages can be activated by many factors such as gut-derived bacterial components and factors released from damaged hepatocytes. Macrophage polarization toward a proinflammatory phenotype (M1) represents an important event in the disease progression of nonalcoholic fatty liver disease (NAFLD). However, the underlying molecular mechanisms remain incompletely understood. Exosomes have been identified as important mediators for cell-cell communication by transferring various biological components such as microRNAs (miRs), proteins, and lipids. The role of exosomes in crosstalk between hepatocytes and macrophages in disease progression of NAFLD is yet to be explored. Approach and results In the present study, we reported that lipotoxic injury-induced release of hepatocyte exosomes enriched with miR-192-5p played a critical role in the activation of M1 macrophages and hepatic inflammation. Serum miR-192-5p levels in patients with NAFLD positively correlated with hepatic inflammatory activity score and disease progression. Similarly, the serum miR-192-5p level and the number of M1 macrophages, as well as the expression levels of the hepatic proinflammatory mediators, were correlated with disease progression in high-fat high-cholesterol diet-fed rat models. Lipotoxic hepatocytes released more miR-192-5p-enriched exosomes than controls, which induced M1 macrophage (cluster of differentiation 11b-positive [CD11b+ ]/CD86+ ) activation and increase of inducible nitric oxide synthase, interleukin 6, and tumor necrosis factor alpha expression. Furthermore, hepatocyte-derived exosomal miR-192-5p inhibited the protein expression of the rapamycin-insensitive companion of mammalian target of rapamycin (Rictor), which further inhibited the phosphorylation levels of Akt and forkhead box transcription factor O1 (FoxO1) and resulted in activation of FoxO1 and subsequent induction of the inflammatory response. Conclusions Hepatocyte-derived exosomal miR-192-5p plays a critical role in the activation of proinflammatory macrophages and disease progression of NAFLD through modulating Rictor/Akt/FoxO1 signaling. Serum exosomal miR-192-5p represents a potential noninvasive biomarker and therapeutic target for nonalcoholic steatohepatitis.
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- 2020
13. Prevalence, clinical characteristics, risk factors, and indicators for lean Chinese adults with nonalcoholic fatty liver disease
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Rui-Nan Zhang, Ying Hu, Qin Pan, Rui-Xu Yang, Guang-Yu Chen, Chao Sun, Jian-Gao Fan, and Jing Zeng
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Male ,China ,medicine.medical_specialty ,Polymorphism, Single Nucleotide ,digestive system ,Triglyceride ,Gastroenterology ,Body Mass Index ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Liver Function Tests ,Reference Values ,Risk Factors ,Retrospective Study ,Internal medicine ,Nonalcoholic fatty liver disease ,Prevalence ,Humans ,Mass Screening ,Medicine ,Triglycerides ,Ultrasonography ,Fatty liver index ,business.industry ,nutritional and metabolic diseases ,Chinese adults ,gamma-Glutamyltransferase ,General Medicine ,Middle Aged ,medicine.disease ,digestive system diseases ,Liver ,Body max index ,chemistry ,030220 oncology & carcinogenesis ,Waist circumference ,Female ,Lean ,030211 gastroenterology & hepatology ,business ,Biomarkers ,Non-alcoholic fatty liver disease - Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases in the world. Nowadays, the percentage of non-obese or lean patients with NAFLD is increasing. NAFLD in non-obese populations, especially the lean subgroup with a normal waist circumference (WC), might lead to more problems than obese individuals, as these individuals may not visit clinics for NAFLD diagnosis or ignore the diagnosis of NAFLD. If the precise characteristics of these populations, especially the lean subgroup, are identified, the clinicians would be able to provide more appropriate advice and treatment to these populations. AIM To investigate the prevalence, clinical characteristics, risk factors, and possible indicators for NAFLD in lean Chinese adults with a normal WC. METHODS People without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included. Their fatty liver index (FLI), abdominal ultrasonography results, and controlled attenuation parameter were all assessed. Genotyping for single-nucleotide polymorphisms associated with NAFLD was performed in another small group consisting of biopsy-proven NAFLD subjects and healthy controls. RESULTS A total of 2715 subjects who underwent routine health examinations were included in the study. Among 810 lean participants with a normal WC, 142 (17.5%) fulfilled the diagnostic criteria for NAFLD. Waist-height ratio, hemoglobin, platelets, and triglycerides were significant factors associated with the presence of NAFLD in these participants. The appropriate cut-off value of the FLI score in screening for NAFLD in the lean subjects with a normal WC was 25.15, which had a 77.8% sensitivity and 75.9% specificity. There was no significant difference in the single-nucleotide polymorphisms in the SIRT1, APOC3, PNPLA3, AGTR1, and PPARGC1A genes between lean subjects with and without NAFLD (P < 0.05). CONCLUSION NAFLD is not uncommon in lean Chinese adults even with a normal WC. Metabolic factors, rather than genetic factors, may play important roles in the development of NAFLD in this population. A lower cut-off value of the FLI score in screening for NAFLD should be used for lean Chinese adults with a normal WC.
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- 2020
14. Association of maternal obesity and gestational diabetes mellitus with overweight/obesity and fatty liver risk in offspring
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Jing Zeng, Feng Shen, Zi-Yuan Zou, Rui-Xu Yang, Qian Jin, Jing Yang, Guang-Yu Chen, and Jian-Gao Fan
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Adult ,China ,Pediatric Obesity ,Gastroenterology ,General Medicine ,Overweight ,Body Mass Index ,Cohort Studies ,Fatty Liver ,Obesity, Maternal ,Diabetes, Gestational ,Pregnancy ,Risk Factors ,Birth Weight ,Humans ,Female ,Prospective Studies ,Child - Abstract
Childhood obesity and fatty liver are associated with adverse outcomes such as diabetes, metabolic syndrome, and cardiovascular diseases in adulthood. It is very important to identify relevant risk factors and intervene as early as possible. At present, the relationship between maternal and offspring metabolic factors is conflicting.To estimate the association of maternal obesity and gestational diabetes mellitus (GDM) with overweight/obesity and fatty liver risk in offspring at 8 years of age.The prospective study included mothers who all had a 75-g oral glucose tolerance test at 24-28 wk of gestation and whose offspring completed follow-up at 8 years of age. Offspring birth weight, sex, height, weight, and body mass index (BMI) were measured and calculated. FibroScan-502 examination with an M probe (Echosens, Paris, France) was prospectively conducted in offspring aged 8 years from the Shanghai Prenatal Cohort Study.A total of 430 mother-child pairs were included in the analysis. A total of 62 (14.2%) mothers were classified as obese, and 48 (11.1%) were classified as having GDM. The mean age of the offspring at follow-up was 8 years old. Thirty-seven (8.6%) offspring were overweight, 14 (3.3%) had obesity, and 60 (14.0%) had fatty liver. The prevalence of overweight, obesity and fatty liver in offspring increased significantly across maternal BMI quartiles (allThis study showed that maternal obesity can increase the odds of overweight/obesity and fatty liver in offspring, and GDM status also increases the odds of overweight/obesity in offspring. Weight management and glycemic control before and during pregnancy need to be highlighted in primary prevention of pediatric obesity and fatty liver.
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- 2021
15. Prevalence and characteristics of MAFLD in Chinese adults aged 40 years or older: A community-based study
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Jing Zeng, Li Qin, Qian Jin, Rui-Xu Yang, Guang Ning, Qing Su, Zhen Yang, and Jian-Gao Fan
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Adult ,China ,Cross-Sectional Studies ,Hepatology ,Diabetes Mellitus, Type 2 ,Metabolic Diseases ,Non-alcoholic Fatty Liver Disease ,Gastroenterology ,Prevalence ,Humans ,Fibrosis - Abstract
Nonalcoholic fatty liver disease (NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease (MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults.A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratified cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected.A total of 9927 subjects were included in this study. The prevalence of MAFLD (40.3%) was significantly higher than that of NAFLD (36.9%) (P0.05). MAFLD was highly prevalent in type 2 diabetes mellitus (T2DM) (53.8%), impaired fasting glucose (35.7%) and impaired glucose tolerance (40.9%). High risk of advanced fibrosis based on fibrosis-4 was highly prevalent (14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481 (35.1%) fulfilled the diagnostic criteria for MAFLD and NAFLD (MAFLD+NAFLD+), 521 (5.2%) MAFLD+NAFLD-, and 181 (1.8%) MAFLD-NAFLD+. The MAFLD+NAFLD- group had more significant metabolic disorders than those in the MAFLD+NAFLD+ group (all P0.05). Among MAFLD-NAFLD+ subjects, 82.9% had metabolic disorders.The new definition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.
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- 2021
16. Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression
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Feng-Zhi Xin, Xiao-Lin Liu, Yuanwen Chen, Jian-Gao Fan, Da Zhou, Ze-Hua Zhao, Huiping Zhou, Rui-Xu Yang, and Qin Pan
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Male ,0301 basic medicine ,Clinical Biochemistry ,lcsh:Medicine ,Biochemistry ,Mice ,chemistry.chemical_compound ,Glucagon-Like Peptide 1 ,Non-alcoholic Fatty Liver Disease ,lcsh:QD415-436 ,Receptor ,biology ,digestive, oral, and skin physiology ,Fatty liver ,Sodium butyrate ,Biological activity ,Hep G2 Cells ,3. Good health ,Intestines ,Liver ,Disease Progression ,Molecular Medicine ,Female ,hormones, hormone substitutes, and hormone antagonists ,Adult ,endocrine system ,medicine.medical_specialty ,Down-Regulation ,Diet, High-Fat ,Glucagon-Like Peptide-1 Receptor ,Article ,lcsh:Biochemistry ,03 medical and health sciences ,Downregulation and upregulation ,Internal medicine ,medicine ,Animals ,Humans ,Molecular Biology ,business.industry ,lcsh:R ,medicine.disease ,digestive system diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,Insulin receptor ,030104 developmental biology ,Endocrinology ,chemistry ,biology.protein ,Butyric Acid ,Steatosis ,Steatohepatitis ,business - Abstract
Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH., Fatty liver disease: A gutsy way to prevent disease progression A treatment for non-alcoholic fatty liver disease that incorporates a metabolite found in the gut could prevent progression to a more serious liver condition. Drugs that enhance the activity of glucagon-like peptide-1 (GLP-1), a protein involved in regulating metabolic processes, have shown promise in targeting non-alcoholic fatty liver disease and the more serious condition, steatohepatitis. However, some patients appear resistant to treatment. Jian-Gao Fan at Shanghai Jiao Tong University in China, Huiping Zhou at McGuire VA Medical Center in Richmond, USA, and co-workers demonstrated that a gut metabolite called sodium butyrate may help encourage responsiveness to GLP-1 treatment. The team found that liver GLP-1R expression was considerably reduced in patients with liver disease compared with healthy controls. Experiments on mouse models showed that treatment incorporating sodium butyrate improved GLP-1R levels and reduced fatty liver deposits.
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- 2018
17. The burden and sexual dimorphism with nonalcoholic fatty liver disease in Asian children: A systematic review and meta-analysis.
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Zi-Yuan Zou, Jing Zeng, Tian-Yi Ren, Lei-Jie Huang, Meng-Yu Wang, Yi-Wen Shi, Rui-Xu Yang, Qian-Ren Zhang, and Jian-Gao Fan
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NON-alcoholic fatty liver disease ,ASIANS ,JUVENILE diseases ,SEXUAL dimorphism ,OVERWEIGHT children - Abstract
Background: Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized. Methods: We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses and meta-regression were all performed. Results: Thirty-three study populations were finally included. Nine of them comprising 20 595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004 to 2010 to the last decade. Male predominant trends were observed in paediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after 10 years of age, boys were more prone to have NAFLD than girls (OR = 1.75; P = .0012). In addition, the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n = 2610), overweight (16.72%, 95% CI 7.07%-34.65%, n = 1265) and obese children (50.13%, 95% CI 41.99%-58.27%, n = 6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (P = .0396) and body mass index (P < .0001) were positively correlated with prevalent NAFLD. Conclusions: In Asia, paediatric NAFLD is becoming prevalent over the recent decades, particularly among obese children and boys after 10 years old. The hormonal and chromosomal origins of paediatric NAFLD dimorphism need further investigation. [ABSTRACT FROM AUTHOR]
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- 2022
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18. PNPLA3 rs139051 is associated with phospholipid metabolite profile and hepatic inflammation in nonalcoholic fatty liver disease
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Rui-Xu Yang, Rui-Nan Zhang, Qin Pan, Ji-Jun Luo, and Hai-Xia Cao
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0301 basic medicine ,medicine.medical_specialty ,Metabolite ,Phospholipid ,Single-nucleotide polymorphism ,Inflammation ,Hepatic inflammation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Patatin-like phospholipase domain containing 3 ,business.industry ,General Medicine ,Basic Study ,medicine.disease ,Single nucleotide polymorphism ,030104 developmental biology ,Endocrinology ,chemistry ,lipids (amino acids, peptides, and proteins) ,030211 gastroenterology & hepatology ,medicine.symptom ,business - Abstract
AIM To investigate the effect of PNPLA3 polymorphisms on serum lipidomics and pathological characteristics in nonalcoholic fatty liver disease (NAFLD). METHODS Thirty-four biopsy-proven NAFLD patients from Northern, Central, and Southern China were subjected to stratification by genotyping their single nucleotide polymorphisms (SNPs) in PNPLA3. Ultra performance liquid chromatographytandem mass spectrometry was then employed to characterize the effects of PNPLA3 SNPs on serum lipidomics. In succession, correlation analysis revealed the association of PNPLA3-related lipid profile and hepatic pathological characteristics on a basis of steatosis, activity, and fibrosis assessment. The variant-based scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was finally performed so as to uncover the actions of lipidomics-affecting PNPLA3 SNPs in NAFLD-specific pathological alterations. RESULTS PNPLA3 SNPs (rs139051, rs738408, rs738409, rs 2072906, rs2294918, rs2294919, and rs4823173) demonstrated extensive association with the serum lipidomics, especially phospholipid metabolites [lysophosphatidylcholine (LPC), lysophosphatidylcholine plasmalogen (LPCO), lysophosphatdylethanolamine (LPE), phosphatidylcholine (PC), choline plasmalogen (PCO), phosphatidylethanolamine (PE), ethanolamine plasmalogen (PEO)], of NAFLD patients. PNPLA3 rs139051 (A/A genotype) and rs2294918 (G/G genotype) dominated the up-regulatory effect on phospholipids of LPCs (LPC 17:0, LPC 18:0, LPC 20:0, LPC 20:1, LPC 20:2) and LPCOs (LPC O-16:1, LPC O-18:1). Moreover, subjects with high-level LPCs/LPCOs were predisposed to low-grade lobular inflammation of NAFLD (rho: -0.407 to -0.585, P < 0.05-0.001). The significant correlation of PNPLA3 rs139051 and inflammation grading [A/A vs A/G + G/G: 0.50 (0.00, 1.75) vs 1.50 (1.00, 2.00), P < 0.05] further demonstrated its pathological role based on the modulation of phospholipid metabolite profile. CONCLUSION The A/A genotype at PNPLA3 rs139051 exerts an up-regulatory effect on serum phospholipids of LPCs and LPCOs, which are associated with low-grade lobular inflammation of NAFLD.
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- 2018
19. miR-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1
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Rui-Xu Yang, Bao-Can Wang, Qin Pan, Ze-Hua Zhao, Rui-Nan Zhang, Hai-Xia Cao, Da Zhou, Jian-Gao Fan, Feng-Zhi Xin, and Xiao-Lin Liu
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0301 basic medicine ,Male ,medicine.medical_specialty ,Palmitic Acid ,Down-Regulation ,Diet, High-Fat ,Palmitic acid ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Cell Line, Tumor ,medicine ,Oil Red O ,Animals ,Humans ,RNA, Small Interfering ,Stearoyl-CoA desaturase 1 ,Reporter gene ,Triglyceride ,Chemistry ,High fat diet ,Lipogenesis ,Fatty liver ,Gastroenterology ,Lipid metabolism ,General Medicine ,Transfection ,Lipid synthesis ,Basic Study ,Liraglutide ,medicine.disease ,Rats ,Up-Regulation ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,Endocrinology ,Liver ,Gene Knockdown Techniques ,Stearoyl-CoA desaturase-1 ,miR-192-5p ,Stearoyl-CoA Desaturase - Abstract
AIM To evaluate the levels of miR-192-5p in non-alcoholic fatty liver disease (NAFLD) models and demonstrate the role of miR-192-5p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet (HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic miR-192-5p and stearoyl-CoA desaturase 1 (SCD-1) levels were measured. MiR-192-5p mimic and inhibitor and SCD-1 siRNA were transfected into Huh7 cells exposed to palmitic acid (PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays. RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic miR-192-5p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection (P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of miR-192-5p and SCD-1 protein levels, respectively (P < 0.01). Transfection with miR-192-5p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively (P < 0.01). Luciferase activity was suppressed and enhanced by miR-192-5p mimic and inhibitor, respectively, in wild-type SCD-1 (P < 0.01) but not in mutant SCD-1. MiR-192-5p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 siRNA transfection abrogated the lipid deposition aggravated by miR-192-5p inhibitor (P < 0.01). CONCLUSION This study demonstrates that miR-192-5p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.
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- 2017
20. Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with Non-alcoholic Fatty Liver Disease and Chronic Hepatitis B
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Feng Shen, Zhen Yang, Wanlu Sun, Jian-Gao Fan, Guowang Xu, Qin Pan, Rui-Xu Yang, Qing Su, and Chunxiu Hu
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,lcsh:Medicine ,Biology ,Chronic liver disease ,Gastroenterology ,digestive system ,Article ,03 medical and health sciences ,Hepatitis B, Chronic ,0302 clinical medicine ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Tandem Mass Spectrometry ,Internal medicine ,medicine ,Humans ,Metabolomics ,lcsh:Science ,Chromatography, High Pressure Liquid ,Triglycerides ,Multidisciplinary ,Fatty liver ,lcsh:R ,Reproducibility of Results ,nutritional and metabolic diseases ,Middle Aged ,Hepatitis B ,medicine.disease ,Lipids ,digestive system diseases ,Fatty Liver ,030104 developmental biology ,ROC Curve ,Alanine transaminase ,Immunology ,biology.protein ,Female ,030211 gastroenterology & hepatology ,lcsh:Q ,Steatosis ,Metabolic syndrome ,Steatohepatitis ,Biomarkers - Abstract
Chronic liver disease is associated with lipid metabolic disruption. We carried out a study to determine serum lipidomic features of patients with non-alcoholic fatty liver disease (NAFLD) and active chronic hepatitis B (CHB) and explored the biomarkers for non-alcoholic steatohepatitis (NASH). Serum lipidomic profiles of healthy controls (n = 23) and of biopsy–proven NAFLD (n = 42), CHB with NAFLD (n = 22) and without NAFLD (n = 17) were analyzed by ultra-performance liquid chromatography–tandem mass spectrometry. There were distinct serum lipidome between groups of NAFLD and CHB without NAFLD. Most of the neutral lipids and ceramide were elevated in the NAFLD group but were decreased in the CHB without NAFLD group. Plasmalogens were decreased in both groups. Triacylglycerols (TAGs) with lower carbon numbers and double bonds were increased in subjects with NASH. Serum monounsaturated TAG was a significant predictor of NASH (OR = 3.215; 95%CI 1.663–6.331) and positively correlated with histological activity (r = 0.501; P
- Published
- 2017
21. Clostridium butyricumB1 alleviates high-fat diet-induced steatohepatitis in mice via enterohepatic immunoregulation
- Author
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Qin Pan, Xiao-Lin Liu, Jian-Gao Fan, Chang Liu, Rui-Xu Yang, Yuanwen Chen, and Da Zhou
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Butyrate ,03 medical and health sciences ,chemistry.chemical_compound ,Immune system ,Internal medicine ,medicine ,Clostridium butyricum ,Hepatology ,biology ,business.industry ,Monocyte ,Gastroenterology ,Interleukin ,Sodium butyrate ,biology.organism_classification ,medicine.disease ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Immunology ,Tumor necrosis factor alpha ,Steatohepatitis ,business - Abstract
Background and Aim Enterohepatic immunologic derangement is associated with non-alcoholic steatohepatitis. Here, we investigated whether Clostridium butyricum B1 (CB) would be an effective immune-targeted substance to attenuate steatohepatitis in mice. Methods Thirty mice were randomized into a control group fed with common forage, a high-fat diet (HFD) group fed an HFD for 16 weeks, and an HFD + CB group treated with CB for the latter 8 weeks. Inflammation-associated or metabolism-associated genes in the liver or epididymal fat tissue were quantified; intrahepatic and intestinal immune factors were detected. Further short-chain fatty acids in the cecal contents or liver were measured, and differentiations of T cells in vitro were analyzed. Results Characteristics of non-alcoholic steatohepatitis in the HFD group were obvious and were significantly attenuated in the HFD + CB group. The messenger RNA levels of monocyte chemotactic protein-1 and tumor necrosis factor-α in the liver and epididymal fat tissue were increased in the HFD group compared with the control group and were downregulated in the HFD + CB group. Intrahepatic and intestinal interferon-γ and interleukin (IL)-17 were significantly increased, whereas forkhead box P3, IL-4, and IL-22 were significantly decreased in the HFD group compared with the control group. However, these intrahepatic or intestinal immune changes were reversed after CB intervention. Furthermore, butyrate in the cecal content and liver of the HFD + CB group was significantly elevated. An in vitro investigation showed that sodium butyrate promoted CD4+ T cell differentiation into Th2, Th22, or Treg, whereas it inhibited CD4+ T cell differentiation into Th1 or Th17 under a cytokine milieu, which was mimicked by Trichostatin A. Conclusion Clostridium butyricum B1 could attenuate HFD-induced steatohepatitis in mice partially through butyrate-induced enterohepatic immunoregulation.
- Published
- 2017
22. Effects and therapeutic mechanism of Yinzhihuang on steatohepatitis in rats induced by a high-fat, high-cholesterol diet
- Author
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Feng Zhi Xin, Qin Pan, Ze Hua Zhao, Xiao Lin Liu, Jing Zeng, You Lin Shao, Rui Xu Yang, and Jian-Gao Fan
- Subjects
Male ,non‐alcoholic fatty liver disease ,medicine.medical_specialty ,Aspartate transaminase ,medicine.disease_cause ,Diet, High-Fat ,Cholesterol, Dietary ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Animals ,Aspartate Aminotransferases ,Receptor ,network‐based regulatory model ,Inflammation ,biology ,Fatty acid metabolism ,business.industry ,Lipogenesis ,Gastroenterology ,Alanine Transaminase ,Original Articles ,medicine.disease ,Lipid Metabolism ,Rats ,Disease Models, Animal ,Oxidative Stress ,Endocrinology ,Cholesterol ,chemistry ,Alanine transaminase ,Liver ,030220 oncology & carcinogenesis ,biology.protein ,030211 gastroenterology & hepatology ,Original Article ,Steatohepatitis ,Steatosis ,business ,Oxidative stress ,Chinese traditional medicine ,therapeutic mechanism ,Drugs, Chinese Herbal ,high‐fat high‐cholesterol diet - Abstract
OBJECTIVES We aimed to investigate the therapeutic mechanism of Yinzhihuang (YZH) liquid, a traditional Chinese medicine mainly composed of extracts of four components, on nonalcoholic steatohepatitis (NASH) induced by a high-fat, high-cholesterol diet (HFHCD) in rats. METHODS Altogether 30 Sprague-Dawley rats were randomized into three groups: control, the model group (HFHCD + saline) and the treatment group (HFHCD + YZH). Liver histological features and serum biochemical parameters were assessed by the end of the 16th week. RNA sequencing and protein mass spectrometry detection were performed. The genes and proteins expressed differentially were subjected to KEGG pathway enrichment analysis and included in a network-based regulatory model. RESULTS The weight, liver and fat indices and serum alanine transaminase, aspartate transaminase and total cholesterol levels of the HFHCD + YZH group were all significantly lower than those of the HFHCD + saline group. Moreover, their hepatic steatosis, ballooning and lobular inflammation were relieved, and 64 hepatic genes and 73 hepatic proteins were found to be reversed in their expression patterns after YZH treatment (P
- Published
- 2019
23. Trimethylamine N-oxide attenuates high-fat high-cholesterol diet-induced steatohepatitis by reducing hepatic cholesterol overload in rats
- Author
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Feng-Zhi Xin, Yaqian Xue, Jian-Gao Fan, Qin Pan, Xiao-Lin Liu, Rui-Xu Yang, Da Zhou, and Ze-Hua Zhao
- Subjects
Male ,Drug Evaluation, Preclinical ,Administration, Oral ,Trimethylamine N-oxide ,Gut flora ,Cholesterol, Dietary ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Intestinal Mucosa ,biology ,Chemistry ,Gastroenterology ,General Medicine ,Basic Study ,Endoplasmic Reticulum Stress ,medicine.anatomical_structure ,Cholesterol ,Treatment Outcome ,Liver ,030220 oncology & carcinogenesis ,ABCG5 ,Intestinal cholesterol absorption ,Disease Progression ,030211 gastroenterology & hepatology ,medicine.symptom ,medicine.medical_specialty ,Inflammation ,Gut microbiota ,Diet, High-Fat ,03 medical and health sciences ,Methylamines ,Internal medicine ,medicine ,Animals ,Humans ,Nonalcoholic steatohepatitis ,medicine.disease ,biology.organism_classification ,Small intestine ,Gastrointestinal Microbiome ,Rats ,Disease Models, Animal ,Endocrinology ,Intestinal Absorption ,biology.protein ,Steatohepatitis - Abstract
Background Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. Aim To determine the effect of TMAO on the progression of NASH. Methods A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. Results Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAO-treated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influx-related Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. Conclusion These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.
- Published
- 2019
24. Nitro-oleic acid as a new drug candidate for non-alcoholic steatohepatitis
- Author
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Rui-Xu Yang and Jian-Gao Fan
- Subjects
Research paper ,Chemistry ,Drug candidate ,Non alcoholic ,General Medicine ,Hep G2 Cells ,Pharmacology ,medicine.disease ,Non-alcoholic Steatohepatitis ,Fibrosis ,General Biochemistry, Genetics and Molecular Biology ,Oleic acid ,chemistry.chemical_compound ,Mice ,Non-alcoholic Fatty Liver Disease ,medicine ,Nitro ,Non-invasive liver imaging, liver fibrosis ,Animals ,Steatohepatitis ,Nitro-fatty acids ,Oleic Acid - Abstract
Background Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are reaching global epidemic proportions. Lack of non-invasive diagnostic tools and effective therapies constitute two of the major hurdles for a bona fide treatment and a reversal of NASH progression and/or regression of the disease. Nitro-oleic acid (OA-NO2) has been proven effective in multiple experimental models of inflammation and fibrosis. Thus, the potential benefit of in vivo administration of OA-NO2 to treat advanced NAFLD was tested herein in a model of long-term NASH diet-induced liver damage. Methods Non-invasive imaging (e.g. photoacustic-ultrasound (PA-US)) was pursued to establish advanced experimental model of NASH in mice in which both steatosis and fibrosis were diagnosed prior experimental therapy with OA-NO2. Experimental controls included equimolar amounts of the non-nitrated oleic acid (OA). CLAMS and NMR-based analysis was used for energy metabolism. Findings CLAMS and NMR-based analysis demonstrates that OA-NO2 improves body composition and energy metabolism and inhibits hepatic triglyceride (TG) accumulation. Photoacoustic-ultrasound imaging revealed a robust inhibition of liver steatosis and fibrosis by OA-NO2. RNA-sequencing analysis uncovered inflammation and fibrosis as major pathways suppressed by OA-NO2 administration, as well as regulation of lipogenesis and lipolysis pathways, with a robust inhibition of SREBP1 proteolytic activation and subsequent lipogenesis gene expression by OA-NO2. These results were further supported by histological analysis and quantification of lipid accumulation, lobular inflammation (F4/80 staining) and fibrosis (collagen deposition, αSMA staining) as well as established parameters of liver damage (ALT). In vitro studies indicate that OA-NO2 inhibits TG biosynthesis and accumulation in hepatocytes and inhibits fibrogenesis in human stellate cells. Interpretation OA-NO2 improve steatohepatitis and fibrosis and may constitute an effective therapeutic approach against advanced NAFLD that warrants further clinical evaluation.
- Published
- 2019
25. Altered DNA Methylation Sites in Peripheral Blood Leukocytes from Patients with Simple Steatosis and Nonalcoholic Steatohepatitis (NASH)
- Author
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Rui-Xu Yang, Qin Pan, Rui-Nan Zhang, Hai-Xia Cao, Jian-Gao Fan, Feng Shen, Guang-Yu Chen, Jiayu Wu, and Da Zhou
- Subjects
0301 basic medicine ,Adult ,Male ,Epigenomics ,medicine.medical_specialty ,Inflammation ,Gastroenterology ,digestive system ,Epigenesis, Genetic ,03 medical and health sciences ,Liver disease ,Fibrosis ,Non-alcoholic Fatty Liver Disease ,Clinical Research ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Leukocytes ,Humans ,Gene ,business.industry ,General Medicine ,DNA ,DNA Methylation ,Middle Aged ,medicine.disease ,digestive system diseases ,DNA-Binding Proteins ,Fatty Liver ,030104 developmental biology ,CpG site ,DNA methylation ,CpG Islands ,Female ,Steatosis ,medicine.symptom ,business ,Biomarkers - Abstract
BACKGROUND The aim of this study was to identify DNA methylation sites in peripheral blood leukocytes from patients with histologically confirmed nonalcoholic fatty liver disease (NAFLD) that included simple hepatic steatosis and nonalcoholic steatohepatitis (NASH). MATERIAL AND METHODS DNA was isolated from peripheral blood leukocytes from patients with histologically diagnosed NAFLD (n=35), including simple hepatic steatosis (n=18) and NASH (n=17). Healthy controls included individuals without liver disease (n=30). DNA was hybridized, and DNA methylation was interrogated in an epigenome-wide association study (EWAS). DNA methylation levels (β-values) were correlated with serum lipid profiles, liver enzymes, and liver histology. RESULTS Circulating blood leukocytes from 35 patients with NAFLD (simple steatosis and NASH) contained 65 CpG sites, which represented 60 genes that were differentially methylated when compared with healthy controls. In the simple hepatic steatosis group (n=18), 42 methylated CpG sites were found to be associated with increased levels of serum alanine aminotransferase (ALT), and 32 methylated CpG sites were associated with increased serum lipid profiles. In the NASH group (n=17), when compared with the simple hepatic steatosis group, methylated CpG sites showed significant correlations with the presence of lobular inflammation compared with hepatic steatosis and fibrosis. Six differentially methylated CpG sites were identified in the ACSL4, CRLS1, CTP1A, SIGIRR, SSBP1 and ZNF622 genes, which were associated with histologically confirmed simple hepatic steatosis and NASH. CONCLUSIONS The study identified some key methylated CpG sites from peripheral blood leukocytes, which might be used as serum biomarkers to stratify NAFLD patients into simple hepatic steatosis and NASH.
- Published
- 2018
26. Efficacy of Intragastric Balloons in the Markers of Metabolic Dysfunction-associated Fatty Liver Disease: Results from Meta-analyses
- Author
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Rui-Xu Yang, Jing Zeng, Tian-Yi Ren, Zi-Yuan Zou, Yi-Wen Shi, and Jian-Gao Fan
- Subjects
medicine.medical_specialty ,Intragastric balloon ,Hepatology ,business.industry ,Fatty liver ,Insulin resistance ,Disease ,medicine.disease ,Gastroenterology ,Confidence interval ,law.invention ,Basal (phylogenetics) ,Randomized controlled trial ,law ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Original Article ,Age groups ,Treatment outcome ,business ,Complication - Abstract
Background and Aims Nonalcoholic fatty liver disease, now renamed metabolic dysfunction-associated fatty liver disease (MAFLD), is common in obese patients. Intragastric balloon (IGB), an obesity management tool with low complication risk, might be used in MAFLD treatment but there is still unexplained heterogeneity in results across studies. Methods We conducted a systematic search of 152 citations published up to September 2020. Meta-analyses, stratified analyses, and meta-regression were performed to evaluate the efficacy of IGB on homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT), and to identify patients most appropriate for IGB therapy. Results Thirteen observational studies and one randomized controlled trial met the inclusion criteria (624 participants in total). In the overall estimate, IGB therapy significantly improved the serum markers change from baseline to follow-up [HOMA-IR: 1.56, 95% confidence interval (CI)=1.16–1.95; ALT: 11.53 U/L, 95% CI=7.10–15.96; AST: 6.79 U/L, 95% CI=1.69–11.90; GGT: 10.54 U/L, 95% CI=6.32–14.75]. In the stratified analysis, there were trends among participants with advanced age having less change in HOMA-IR (1.07 vs. 1.82). The improvement of insulin resistance and liver biochemistries with swallowable IGB therapy was no worse than that with endoscopic IGB. Multivariate meta-regression analyses showed that greater HOMA-IR loss was predicted by younger age (p=0.0107). Furthermore, effectiveness on ALT and GGT was predicted by basal ALT (p=0.0004) and GGT (p=0.0026), respectively. Conclusions IGB is effective among the serum markers of MAFLD. Younger patients had a greater decrease of HOMA-IR after IGB therapy.
- Published
- 2021
27. Clostridium butyricum B1 alleviates high-fat diet-induced steatohepatitis in mice via enterohepatic immunoregulation
- Author
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Da, Zhou, Qin, Pan, Xiao-Lin, Liu, Rui-Xu, Yang, Yuan-Wen, Chen, Chang, Liu, and Jian-Gao, Fan
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Tumor Necrosis Factor-alpha ,Cell Differentiation ,Diet, High-Fat ,Fatty Acids, Volatile ,Fatty Liver ,Intestines ,Mice, Inbred C57BL ,Butyrates ,Liver ,Clostridium butyricum ,Animals ,Cytokines ,RNA, Messenger ,Intestinal Mucosa ,Cells, Cultured ,Chemokine CCL2 - Abstract
Enterohepatic immunologic derangement is associated with non-alcoholic steatohepatitis. Here, we investigated whether Clostridium butyricum B1 (CB) would be an effective immune-targeted substance to attenuate steatohepatitis in mice.Thirty mice were randomized into a control group fed with common forage, a high-fat diet (HFD) group fed an HFD for 16 weeks, and an HFD + CB group treated with CB for the latter 8 weeks. Inflammation-associated or metabolism-associated genes in the liver or epididymal fat tissue were quantified; intrahepatic and intestinal immune factors were detected. Further short-chain fatty acids in the cecal contents or liver were measured, and differentiations of T cells in vitro were analyzed.Characteristics of non-alcoholic steatohepatitis in the HFD group were obvious and were significantly attenuated in the HFD + CB group. The messenger RNA levels of monocyte chemotactic protein-1 and tumor necrosis factor-α in the liver and epididymal fat tissue were increased in the HFD group compared with the control group and were downregulated in the HFD + CB group. Intrahepatic and intestinal interferon-γ and interleukin (IL)-17 were significantly increased, whereas forkhead box P3, IL-4, and IL-22 were significantly decreased in the HFD group compared with the control group. However, these intrahepatic or intestinal immune changes were reversed after CB intervention. Furthermore, butyrate in the cecal content and liver of the HFD + CB group was significantly elevated. An in vitro investigation showed that sodium butyrate promoted CD4Clostridium butyricum B1 could attenuate HFD-induced steatohepatitis in mice partially through butyrate-induced enterohepatic immunoregulation.
- Published
- 2016
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