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Pu J, Zhao Y, Zhang S, Wu T, Liu R, Yuan T, He S, Hao Q, Zhu H. Mapping the knowledge domains of literature on hepatocellular carcinoma and liver failure: a bibliometric approach. Front Oncol 2025; 15:1529297. [PMID: 40308492 PMCID: PMC12040667 DOI: 10.3389/fonc.2025.1529297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 03/27/2025] [Indexed: 05/02/2025] Open
Abstract
Background Hepatocellular carcinoma (HCC) accounts for 75-85% of primary liver cancers, with its incidence continually rising, posing a threat to socio-economic development. Currently, liver resection is the standard treatment for HCC. However, post-hepatectomy liver failure (PHLF) is a severe and formidable postoperative complication that increases patients' medical expenses and mortality risk. Additionally, liver failure can occur at any stage of HCC development, severely affecting patients' quality of life and prognosis. Method Using the Web of Science Core Collection, this bibliometric study analyzed English articles and reviews on HCC and liver failure from 2003 to 2023. Bibliometric tools like CiteSpace, VOSviewer, and R-studio were employed for data visualization and analysis, focusing on publication trends, citation metrics, explosive intensity, and collaborative networks. Use the Comparative Toxicogenomics and Genecards databases to screen for genes related to liver failure, and perform enrichment analyses using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PubMed on the identified differentially expressed genes. Results The study identified a significant increase in publications on HCC and liver failure, with key contributions from journals such as the World Journal of Gastroenterology and the Journal of Hepatology. The United States, China, and Japan were the leading countries in research output. Prominent authors and institutions, including Kudo Masatoshi and Sun Yat-sen University, were identified. Enrichment analysis showed drug metabolism, oxidative stress, lipid metabolism, and other pathways are closely related to this field. Research hotspots included risk prediction models and novel therapies. Conclusion This bibliometric analysis highlights the growing research interest and advancements in HCC and liver failure. Future research should focus on improving risk prediction, developing new therapies, and enhancing international collaboration to address these critical health issues.
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Affiliation(s)
- Jun Pu
- Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Medical School of Nantong University, Nantong, China
| | - Yamin Zhao
- Department of Cardiology, Nantong Second People's Hospital, Nantong, China
| | - Siming Zhang
- Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Medical School of Nantong University, Nantong, China
- Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan
| | - Tianqi Wu
- Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Medical School of Nantong University, Nantong, China
| | - Ruizi Liu
- Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Medical School of Nantong University, Nantong, China
| | - Tianyi Yuan
- Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Medical School of Nantong University, Nantong, China
| | - Songnian He
- Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Medical School of Nantong University, Nantong, China
| | - Qingyu Hao
- Department of Cardiology, Infectious Disease Hospital of Heilongjiang Province, Harbin, China
| | - Haixia Zhu
- Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Medical School of Nantong University, Nantong, China
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Zeljkovic A, Vekic J, Stefanovic A. Obesity and dyslipidemia in early life: Impact on cardiometabolic risk. Metabolism 2024; 156:155919. [PMID: 38653373 DOI: 10.1016/j.metabol.2024.155919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 04/19/2024] [Accepted: 04/19/2024] [Indexed: 04/25/2024]
Abstract
Childhood obesity with its growing prevalence worldwide presents one of the most important health challenges nowadays. Multiple mechanisms are involved in the development of this condition, as well as in its associations with various cardiometabolic complications, such as insulin resistance, diabetes, metabolic dysfunction-associated steatotic liver disease and cardiovascular diseases. Recent findings suggest that childhood obesity and associated dyslipidemia at least partly originate from epigenetic modifications that take place in the earliest periods of life, namely prenatal and perinatal periods. Hence, alterations of maternal metabolism could be fundamentally responsible for fetal and neonatal metabolic programming and consequently, for metabolic health of offspring in later life. In this paper, we will review recent findings on the associations among intrauterine and early postnatal exposure to undesirable modulators of metabolism, development of childhood obesity and later cardiometabolic complications. Special attention will be given to maternal dyslipidemia as a driven force for undesirable epigenetic modulations in offspring. In addition, newly proposed lipid biomarkers of increased cardiometabolic risk in obese children and adolescents will be analyzed, with respect to their predictive potential and clinical applicability.
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Affiliation(s)
- Aleksandra Zeljkovic
- Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, Belgrade, Serbia
| | - Jelena Vekic
- Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, Belgrade, Serbia.
| | - Aleksandra Stefanovic
- Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, Belgrade, Serbia
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Huneault HE, Chen CY, Cohen CC, Liu X, Jarrell ZR, He Z, DeSantos KE, Welsh JA, Maner-Smith KM, Ortlund EA, Schwimmer JB, Vos MB. Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease. Metabolites 2024; 14:191. [PMID: 38668319 PMCID: PMC11052520 DOI: 10.3390/metabo14040191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 03/21/2024] [Accepted: 03/26/2024] [Indexed: 04/28/2024] Open
Abstract
Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.
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Affiliation(s)
- Helaina E. Huneault
- Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; (J.A.W.); (M.B.V.)
| | - Chih-Yu Chen
- Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA; (C.-Y.C.); (X.L.); (E.A.O.)
| | - Catherine C. Cohen
- Section of Nutrition, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (C.C.C.); (K.M.M.-S.)
| | - Xueyun Liu
- Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA; (C.-Y.C.); (X.L.); (E.A.O.)
| | - Zachery R. Jarrell
- Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, GA 30322, USA;
| | - Zhulin He
- Pediatric Biostatistics Core, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA;
| | - Karla E. DeSantos
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA;
- Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
| | - Jean A. Welsh
- Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; (J.A.W.); (M.B.V.)
- Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
| | - Kristal M. Maner-Smith
- Section of Nutrition, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (C.C.C.); (K.M.M.-S.)
| | - Eric A. Ortlund
- Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA; (C.-Y.C.); (X.L.); (E.A.O.)
| | - Jeffrey B. Schwimmer
- Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, CA 92123, USA;
- Department of Pediatrics, School of Medicine, University of California, San Diego, CA 92093, USA
| | - Miriam B. Vos
- Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; (J.A.W.); (M.B.V.)
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA;
- Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
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Jiang X, Hu R, Huang Y, Xu Y, Zheng Z, Shi Y, Miao J, Liu Y. Fructose aggravates copper-deficiency-induced non-alcoholic fatty liver disease. J Nutr Biochem 2023; 119:109402. [PMID: 37311490 PMCID: PMC11186518 DOI: 10.1016/j.jnutbio.2023.109402] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 05/28/2023] [Accepted: 06/07/2023] [Indexed: 06/15/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD), is the most common cause of chronic liver disease, affecting 24% of the global population. Accumulating evidence demonstrates that copper deficiency (CuD) is implicated in the development of NAFLD, besides, high fructose consumption by promoting inflammation contributes to NAFLD. However, how CuD and/or fructose (Fru) causes NAFLD is not clearly delineated. The present study aims to investigate the role of CuD and/or fructose supplement on hepatic steatosis and hepatic injury. We established a CuD rat model by feeding weaning male Sprague-Dawley rats for 4 weeks with CuD diet. Fructose was supplemented in drinking water. We found the promoting role of CuD or Fructose (Fru) in the progress of NAFLD, which was aggravated by combination of the two. Furthermore, we presented the alteration of hepatic lipid profiles (including content, composition, and saturation), especially ceramide (Cer), cardiolipin (CL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was closely associated with CuD and/or Fru fed induced-NAFLD in rat models. In conclusion, insufficient copper intake or excessive fructose supplement resulted in adverse effects on the hepatic lipid profile, and fructose supplement causes a further hepatic injury in CuD-induced NAFLD, which illuminated a better understanding of NAFLD.
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Affiliation(s)
- Xin Jiang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, P.R. China
| | - Ruixiang Hu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, P.R. China
| | - Yipu Huang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, P.R. China
| | - Yi Xu
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, P.R. China
| | - Zhirui Zheng
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, P.R. China
| | - Yuansen Shi
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, P.R. China
| | - Ji Miao
- Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
| | - Yun Liu
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, P.R. China.
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Yang X, Sun L, Feng D, Deng Y, Liao W. A Lipidomic Study: Nobiletin ameliorates hepatic steatosis through regulation of lipid alternation. J Nutr Biochem 2023; 118:109353. [PMID: 37116815 DOI: 10.1016/j.jnutbio.2023.109353] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 11/15/2022] [Accepted: 04/10/2023] [Indexed: 04/30/2023]
Abstract
Hepatic lipidome has been given emphasis for years since hepatic steatosis is the most remarkable character of nonalcoholic fatty liver diseases, an increasingly serious health issue worldwide. Nobiletin (NOB), one of the citrus flavonoids, exerted outstanding effect on lipid metabolism disorder. However, the underlying mechanism of NOB exerting effect on hepatic lipid alternation remains unclear. In this study, the animal model was built by feeding APOE-/- mice with high fat diet (HFD). The results of Oil Red O-stained liver section and the biochemical assay of lipid parameters confirmed the protective effect of NOB on hepatic steatosis and global lipid metabolism disorder in APOE-/- mice. The hepatic lipidomic study revealed a total of 958 lipids significantly altered by HFD and a total of 86, 116, 212 lipid metabolites changed by L-NOB (50 mg/kg/d NOB), M-NOB (100 mg/kg/d NOB) and H-NOB (200 mg/kg/d NOB) respectively. In the further screening analysis, an amount of 60 lipids were identified as the potential lipid markers of NOB treatment, most of which belonged to glycerophospholipids lipid categories and exhibited obvious correlation with each other and the lipid parameters related to hepatic steatosis. Taken together, our data demonstrated that glycerophospholipids metabolism played an indispensable role in the progression of hepatic steatosis and the protective effect of NOB. Besides, the modulation towards genes involved in lipid synthesis were observed after NOB administration in this study. These finding illustrated the anti-hepatic steatosis effect of NOB based on altering hepatic lipidome, particularly the glycerophospholipids metabolism, and provided a new insight in the pathogenesis of hepatic steatosis.
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Affiliation(s)
- Xushan Yang
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, No.1023 South Shatai Road, Guangzhou, 510515, China
| | - Linye Sun
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, No.1023 South Shatai Road, Guangzhou, 510515, China
| | - Dongliang Feng
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, No.1023 South Shatai Road, Guangzhou, 510515, China
| | - Yudi Deng
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, No.1023 South Shatai Road, Guangzhou, 510515, China
| | - Wenzhen Liao
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, No.1023 South Shatai Road, Guangzhou, 510515, China.
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6
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Zhuge A, Li S, Yuan Y, Han S, Xia J, Wang Q, Wang S, Lou P, Li B, Li L. Microbiota-induced lipid peroxidation impairs obeticholic acid-mediated antifibrotic effect towards nonalcoholic steatohepatitis in mice. Redox Biol 2022; 59:102582. [PMID: 36584600 PMCID: PMC9830314 DOI: 10.1016/j.redox.2022.102582] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 12/15/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
Obeticholic acid (OCA) has been examined to treat non-alcoholic steatohepatitis (NASH), but has unsatisfactory antifibrotic effect and deficient responsive rate in recent phase III clinical trial. Using a prolonged western diet-feeding murine NASH model, we show that OCA-shaped gut microbiota induces lipid peroxidation and impairs its anti-fibrotic effect. Mechanically, Bacteroides enriched by OCA deconjugates tauro-conjugated bile acids to generate excessive chenodeoxycholic acid (CDCA), resulting in liver ROS accumulation. We further elucidate that OCA reduces triglycerides containing polyunsaturated fatty acid (PUFA-TGs) levels, whereas elevates free PUFAs and phosphatidylethanolamines containing PUFA (PUFA-PEs), which are susceptible to be oxidized to lipid peroxides (notably arachidonic acid (ARA)-derived 12-HHTrE), inducing hepatocyte ferroptosis and activating hepatic stellate cells (HSCs). Inhibiting lipid peroxidation with pentoxifylline (PTX) rescues anti-fibrotic effect of OCA, suggesting combination of OCA and lipid peroxidation inhibitor could be a potential antifibrotic pharmacological approach in clinical NASH-fibrosis.
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Affiliation(s)
- Aoxiang Zhuge
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Shengjie Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yin Yuan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Shengyi Han
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Jiafeng Xia
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Qiangqiang Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Shuting Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Pengcheng Lou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Bo Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Beijing, 100730, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan, 250000, China.
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7
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Riccio S, Melone R, Vitulano C, Guida P, Maddaluno I, Guarino S, Marzuillo P, Miraglia del Giudice E, Di Sessa A. Advances in pediatric non-alcoholic fatty liver disease: From genetics to lipidomics. World J Clin Pediatr 2022; 11:221-238. [PMID: 35663007 PMCID: PMC9134151 DOI: 10.5409/wjcp.v11.i3.221] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/05/2021] [Accepted: 04/02/2022] [Indexed: 02/06/2023] Open
Abstract
As a result of the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) represents a global medical concern in childhood with a closely related increased cardiometabolic risk. Knowledge on NAFLD pathophysiology has been largely expanded over the last decades. Besides the well-known key NAFLD genes (including the I148M variant of the PNPLA3 gene, the E167K allele of the TM6SF2, the GCKR gene, the MBOAT7-TMC4 rs641738 variant, and the rs72613567:TA variant in the HSD17B13 gene), an intriguing pathogenic role has also been demonstrated for the gut microbiota. More interestingly, evidence has added new factors involved in the "multiple hits" theory. In particular, omics determinants have been highlighted as potential innovative markers for NAFLD diagnosis and treatment. In fact, different branches of omics including metabolomics, lipidomics (in particular sphingolipids and ceramides), transcriptomics (including micro RNAs), epigenomics (such as DNA methylation), proteomics, and glycomics represent the most attractive pathogenic elements in NAFLD development, by providing insightful perspectives in this field. In this perspective, we aimed to provide a comprehensive overview of NAFLD pathophysiology in children, from the oldest pathogenic elements (including genetics) to the newest intriguing perspectives (such as omics branches).
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Affiliation(s)
- Simona Riccio
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Rosa Melone
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Caterina Vitulano
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierfrancesco Guida
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Ivan Maddaluno
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
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Riccio S, Valentino MS, Passaro AP, Izzo M, Guarino S, Miraglia del Giudice E, Marzuillo P, Di Sessa A. New Insights from Metabolomics in Pediatric Renal Diseases. CHILDREN (BASEL, SWITZERLAND) 2022; 9:118. [PMID: 35053744 PMCID: PMC8774568 DOI: 10.3390/children9010118] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 01/09/2022] [Accepted: 01/13/2022] [Indexed: 12/11/2022]
Abstract
Renal diseases in childhood form a spectrum of different conditions with potential long-term consequences. Given that, a great effort has been made by researchers to identify candidate biomarkers that are able to influence diagnosis and prognosis, in particular by using omics techniques (e.g., metabolomics, lipidomics, genomics, and transcriptomics). Over the past decades, metabolomics has added a promising number of 'new' biomarkers to the 'old' group through better physiopathological knowledge, paving the way for insightful perspectives on the management of different renal diseases. We aimed to summarize the most recent omics evidence in the main renal pediatric diseases (including acute renal injury, kidney transplantation, chronic kidney disease, renal dysplasia, vesicoureteral reflux, and lithiasis) in this narrative review.
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Affiliation(s)
| | | | | | | | | | | | | | - Anna Di Sessa
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.R.); (M.S.V.); (A.P.P.); (M.I.); (S.G.); (E.M.d.G.); (P.M.)
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9
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Xu S, Wang Y, Li Z, Hua Q, Jiang M, Fan X. LncRNA GAS5 Knockdown Mitigates Hepatic Lipid Accumulation via Regulating MiR-26a-5p/PDE4B to Activate cAMP/CREB Pathway. Front Endocrinol (Lausanne) 2022; 13:889858. [PMID: 35957809 PMCID: PMC9361042 DOI: 10.3389/fendo.2022.889858] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 06/23/2022] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) can be attributed to the dysregulation of hepatic lipid metabolism; however, its cellular and molecular mechanisms remain unclear. This study aims to explore the effect of long non-coding RNA growth arrest specific 5 (GAS5) on hepatic lipid metabolism in fatty liver models. METHODS Obese mice, high fat diet-fed mice and free fatty acid-stimulated cells were used for GAS5 expression detection. GAS5 overexpression or knockdown models were established to elucidate the regulatory function of GAS5 in de novo lipogenesis (DNL) and mitochondrial function. Bioinformatic analyses and dual luciferase assays were used to investigate the interaction between GAS5, miR-26a-5p and phosphodiesterase (PDE) 4B. The involvement of the cyclic adenosine monophosphate (cAMP)/cAMP-response element-binding protein (CREB) pathway was evaluated using H89 and forskolin treatment. RESULTS GAS5 was activated in vitro and in vivo fatty liver models. Knockdown of GAS5 reduced lipid droplet accumulation, DNL associated enzymes and preserved mitochondrial function, while GAS5 overexpression exacerbated hepatic lipid accumulation. Mechanistically, GAS5 sponged miR-26a-5p to increase PDE4B expression and subsequently modulated DNL and mitochondrial function via the cAMP/CREB pathway. CONCLUSION Downregulation of GAS5 can activate the cAMP/CREB pathway through miR-26a-5p/PDE4B axis to mitigate hepatic lipid accumulation. This study provides evidence that downregulation of GAS5 may be a potential therapeutic option for the treatment of NAFLD.
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Affiliation(s)
| | | | | | | | - Miao Jiang
- *Correspondence: Xiaoming Fan, ; Miao Jiang,
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Deng Q, Du L, Zhang Y, Liu G. NEFAs Influence the Inflammatory and Insulin Signaling Pathways Through TLR4 in Primary Calf Hepatocytes in vitro. Front Vet Sci 2021; 8:755505. [PMID: 34966805 PMCID: PMC8710596 DOI: 10.3389/fvets.2021.755505] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/23/2021] [Indexed: 12/21/2022] Open
Abstract
Transition dairy cows are often in a state of negative energy balance because of decreased dry matter intake and increased energy requirements, initiating lipid mobilization and leading to high serum β-hydroxybutyrate (BHBA) and non-esterified fatty acid (NEFAs) levels, which can induce ketosis and fatty liver in dairy cows. Inflammation and insulin resistance are also common diseases in the perinatal period of dairy cows. What is the relationship between negative energy balance, insulin resistance and inflammation in dairy cows? To study the role of non-esterified fatty acids in the nuclear factor kappa beta (NF-κB) inflammatory and insulin signaling pathways through Toll-like receptor 4 (TLR4), we cultured primary calf hepatocytes and added different concentrations of NEFAs to assess the mRNA and protein levels of inflammatory and insulin signaling pathways. Our experiments indicated that NEFAs could activate the NF-κB inflammatory signaling pathway and influence insulin resistance through TLR4. However, an inhibitor of TLR4 alleviated the inhibitory effects of NEFAs on the insulin pathway. In conclusion, all of these results indicate that high-dose NEFAs (2.4 mM) can activate the TLR4/NF-κB inflammatory signaling pathway and reduce the sensitivity of the insulin pathway through the TLR4/PI3K/AKT metabolic axis.
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Affiliation(s)
- Qinghua Deng
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China.,Inner Mongolia Minzu University Key Laboratory for Prevention and Control of Herbivorous Livestock Perinatal Diseases, Tongliao, China
| | - Liyin Du
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China.,Inner Mongolia Minzu University Key Laboratory for Prevention and Control of Herbivorous Livestock Perinatal Diseases, Tongliao, China
| | - Yuming Zhang
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China.,Inner Mongolia Minzu University Key Laboratory for Prevention and Control of Herbivorous Livestock Perinatal Diseases, Tongliao, China
| | - Guowen Liu
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China.,College of Veterinary Medicine, Jilin University, Changchun, China
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