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Zeng L, Tang Y, Huang X, Pei W, Liao Y, Liu J. Combined impact of prognostic nutritional index, fibrinogen-to-albumin ratio, and neutrophil-to-lymphocyte ratio on surgical outcomes and prognosis in hepatocellular carcinoma. Am J Cancer Res 2025; 15:439-451. [PMID: 40084351 PMCID: PMC11897630 DOI: 10.62347/rtmf3105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 02/07/2025] [Indexed: 03/16/2025] Open
Abstract
This study evaluated the predictive value of the prognostic nutritional index (PNI), fibrinogen-to-albumin ratio (FAR), and neutrophil-to-lymphocyte ratio (NLR) for overall survival in hepatocellular carcinoma (HCC) patients. A total of 283 HCC cases from Hunan Provincial People's Hospital were included in the analysis, with 45 additional patients as external validation. The relationship between these indices and patient prognosis was further evaluated using the Kaplan-Meier method and Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of these indices for overall survival (OS) and to determine the optimal cutoff values. ROC curve analysis revealed that the area under the curve (AUC) for PNI, FAR, and NLR was 0.723, 0.857, and 0.872, respectively. Multivariate analysis identified hepatitis history, intraoperative blood transfusion, FAR, NLR, and PNI as independent prognostic factors (all P<0.05). The resulting prediction model demonstrated strong performance in both the training (C-index =0.917) and external validation (C-index =0.853) cohorts, with AUCs of 0.889 and 0.931 for 6-month and 1-year prediction in the validation set, respectively. These findings suggest that preoperative levels of peripheral blood PNI, FAR, and NLR are closely associated with the surgical prognosis of HCC patients. The prognostic prediction model developed based on these indices exhibits good predictive efficacy.
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Affiliation(s)
- Liuhaonan Zeng
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Yixun Tang
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Xiaoling Huang
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Wanmin Pei
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Yongqiong Liao
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Jitong Liu
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
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Xu L, Zhang S, Cao C. The impact of the muscle mass-to-fat ratio on the prognosis of patients undergoing pancreaticoduodenectomy for pancreatic cancer. Kaohsiung J Med Sci 2025; 41:e12928. [PMID: 39717925 PMCID: PMC11827537 DOI: 10.1002/kjm2.12928] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/17/2024] [Accepted: 12/11/2024] [Indexed: 12/25/2024] Open
Abstract
To evaluate the relationship between the muscle mass-to-fat ratio (MMFR) at the third lumbar spine (L3) and overall survival (OS) as well as related complications after pancreaticoduodenectomy (PD) for pancreatic cancer. Patients who underwent PD for pancreatic cancer between March 2017 and May 2023 at the Second Affiliated Hospital of Soochow University were included. Muscle mass and fat content at the L3 were measured by computed tomography. The specific formula that was used to calculate the MMFR was total abdominal muscle area/(subcutaneous adipose tissue area + visceral adipose tissue area), and the optimal cutoff values of the MMFR based on receiver operating characteristic curves were 0.688 for males and 0.382 for females. Patient characteristics were collected, and multivariate analyses were used to evaluate the impact of the MMFR on prognosis. Kaplan-Meier survival curves and log-rank tests were used to compare OS between the high-MMFR and low-MMFR groups. On the basis of the optimal cutoff values, 191 patients were divided into two groups, with 91 patients in the low-MMFR group and 100 patients in the high-MMFR group. The incidence of POPF was significantly greater in the low-MMFR group than in the high-MMFR group. According to multivariate analysis, the MMFR was an independent factor associated with POPF and OS. Patients with low MMFRs had significantly shorter OS and a greater POPF incidence than did those with high MMFRs. The MMFR is an independent predictor of POPF and affects the OS of patients undergoing PD for pancreatic cancer.
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Affiliation(s)
- Long‐Jie Xu
- Department of General SurgeryThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Sheng‐Qiang Zhang
- Department of General SurgeryThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Chun Cao
- Department of General SurgeryThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
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Zi Y, Qin Y, Ma C, Qiao Y, Xu X, Yang Y, He Q, Li M, Liu Y, Gao F. Transcriptome analysis reveals hepatic disordered lipid metabolism, lipotoxic injury, and abnormal development in IUGR sheep fetuses due to maternal undernutrition during late pregnancy. Theriogenology 2024; 226:350-362. [PMID: 38968678 DOI: 10.1016/j.theriogenology.2024.06.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 06/19/2024] [Accepted: 06/23/2024] [Indexed: 07/07/2024]
Abstract
Although lipid metabolism in fetal livers under intrauterine growth restriction (IUGR) conditions has been widely studied, the implications of maternal undernutrition on fetal hepatic lipid metabolism, lipotoxic injury, and abnormal development remain largely unknown. Therefore, this study investigated the effects of maternal undernutrition on disordered hepatic lipid metabolism, lipotoxic injury, and abnormal development in IUGR sheep fetuses using transcriptome analysis. Seventeen singleton ewes were randomly divided into three groups on day 90 of pregnancy: a control group (CG; 0.63 MJ metabolic energy/body weight (ME/BW)0.75/day, n = 5), maternal undernutrition group 1 (MU1; 0.33 MJ ME/BW0.75/day, n = 6), and maternal undernutrition group 2 (MU2; 0.20 MJ ME/BW0.75/day, n = 6). The fetuses were euthanized and recovered on day 130 of pregnancy. The levels of free fatty acids (FFA) in maternal blood (P < 0.01), fetal blood (P < 0.01), and fetal livers (P < 0.05) were increased in the MU1 and MU2 groups, but fetal hepatic triglyceride (TG) levels in the MU2 group (P < 0.01) and β-hydroxybutyrate levels in the MU1 and MU2 groups (P < 0.01) were decreased compared to the CG. Severe inflammatory cell infiltration and increased non-alcoholic fatty liver disease activity scores were observed in MU1 and MU2 fetuses (P < 0.01). Progressive deposition of fetal hepatic reticular fibers and collagen fibers in the fetal livers of the MU1 and MU2 groups and significant hepatic fibrosis were observed in the MU2 fetuses (P < 0.05). Gene set enrichment analysis showed that genes involved in lipid accumulation and FFA beta oxidation were downregulated in both MU groups compared to those in the controls. The fetal liver mRNA expression of the β-oxidation regulator, acetyl-CoA acetyltransferase 1, and the TCA regulator, isocitrate dehydrogenase were reduced in MU1 (P < 0.05) and MU2 (P < 0.01) fetuses, and downregulated mRNA expression of long chain fatty acid CoA ligase 1 (P < 0.05) and glycerol-3-phosphate acyltransferase (P < 0.01) was observed in MU2 fetuses. Differentially expressed genes (DEGs) in MU1 versus CG (360 DEGs) and MU2 versus CG (746 DEGs) were identified using RNA sequencing. Bioinformatics analyses of the 231 intersecting DEGs between MU1 versus CG and MU2 versus CG indicated that neutrophil extracellular traps (NETs) were induced and played a central role in fetal hepatic injury in IUGR sheep. Increased maternal blood myeloperoxidase (MPO) levels (P < 0.01), NE (Elane)-positive areas in fetal liver sections (P < 0.05), and fetal liver MPO protein expression (P < 0.01) were found in the MU1 and MU2 groups; however, MPO levels were reduced in the fetal membrane (P < 0.01) and fetal blood (P < 0.05) in the MU1 group, and in the maternal-fetal placenta and fetal blood in the MU2 group (P < 0.01). Analysis of gene expression trends in the intersecting DEGs between MU1 versus CG (129 DEGs) and MU2 versus CG (515 DEGs) further revealed that 30 hub genes were essential regulators of the G2/M cell cycle, all of which were associated with hepatocellular carcinoma. G0/G1 phase cells of the fetal liver were reduced in the MU1 (P < 0.05) and MU2 (P < 0.01) groups, whereas G2/M phase cells were elevated in the MU1 and MU2 groups (P < 0.01). The representatives of upregulated hub genes and fetal liver protein expression of maternal embryonic leucine zipper kinase and protein regulator of cytokinesis 1 were progressively enhanced in the MU1 and MU2 groups (P < 0.01), and topoisomerase II alpha protein expression in the MU2 group (P < 0.05), as expected. These results indicate that FFA overload, severe lipotoxic injury, and NETs were induced, and disease-promoting regulators of the G2/M cell cycle were upregulated in the fetal liver of IUGR sheep. These findings provide new insights into the pathogenesis of impaired hepatic lipid metabolism and abnormal development and the molecular origin of post-natal liver disease in IUGR due to maternal undernutrition. This information can support the development of new therapeutic strategies.
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Affiliation(s)
- Yang Zi
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China; Shenzheng Institute of Advanced Technology, Chinese Academy of Sciences, Shenzheng, China
| | - Yulong Qin
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Chi Ma
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Yina Qiao
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Xiaoyi Xu
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Yilin Yang
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Qiuyue He
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Mingyue Li
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Yingchun Liu
- College of Life Science, Inner Mongolia Key Laboratory of Biomanufacturing, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Feng Gao
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China.
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Tan Y, Jiang X, Ding X, Wei Z, Song Z, Chen S, Yang P, Zhao D, Wu S, Li Y. Early life exposure to Chinese famine and risk of digestive system cancer in midlife. Appl Physiol Nutr Metab 2024; 49:751-761. [PMID: 38346286 DOI: 10.1139/apnm-2023-0366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
To investigate whether early-life exposure to the Great Famine of 1959-1961 in China was associated with the risk of digestive system cancer. The prospective cohort study involved 17 997 participants from the Kailuan Study (Tangshan, China) that began in 2006. All participants were divided into three groups based on their date of birth. The unexposed group (born from 1 October 1962 to 30 September 1964), fetal-exposed group (born from 1 October 1959 to 30 December 1961), and early-childhood-exposed group (born from 1 October 1956 to 30 December 1958). The Cox proportional hazards model was used to analyze the association between early famine exposure and digestive system cancer. During the mean follow-up period of (10.4 ± 2.2) years, a total of 223 digestive system cancer events occurred. Including 54 cases in the unexposed group (62.14/100 000 person-years), 57 cases in the fetal-exposed group (114.8/100 000 person-years), and 112 cases in the early-childhood-exposure group (122.2/100 000 person-years). After adjusting covariates, compared with the unexposed group, the HR and 95% CI were 1.85 (1.28, 2.69) for participants in the fetal-exposed group and 1.92 (1.38, 2.66) for participants in the early-childhood-exposed group. No interactions were observed in our study. After classifying digestive system cancers, the HR and 95% CI were 2.02 (1.03, 3.97) for colorectal cancer for participants in the fetal-exposed group and 2.55 (1.43, 4.55) for participants in the early-childhood-exposed group. The HR and 95% CI were (1.13, 3.83) of liver cancer for participants in the fetal-exposed group and 1.15 (0.63, 2.10) for participants in the early-childhood-exposed group. Early-life famine exposure was associated with a higher risk of digestive system cancer in adulthood. Fetal-exposed individuals might increase the risk of colorectal cancer and liver cancer, and early childhood-exposed might increase the risk of colorectal cancer.
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Affiliation(s)
- Yizhen Tan
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Xiaozhong Jiang
- Digestive Department, Kailuan General Hospital, Tangshan, China
| | - Xiong Ding
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Zhihao Wei
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Zongshuang Song
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Shuohua Chen
- Department of Cardiology, Kailuan General Hospital, Tangshan, China
| | - Peng Yang
- Department of Neurosurgery, Affiliated Hospital of North China University of Science and Technology, Tangshan, China
| | - Dandan Zhao
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Shouling Wu
- Department of Cardiology, Kailuan General Hospital, Tangshan, China
| | - Yun Li
- School of Public Health, North China University of Science and Technology, Tangshan, China
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Tzeng HT, Lee WC. Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity. Nutrients 2024; 16:1388. [PMID: 38732634 PMCID: PMC11085251 DOI: 10.3390/nu16091388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 04/25/2024] [Accepted: 05/01/2024] [Indexed: 05/13/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent pediatric liver disorder, primarily attributed to dietary shifts in recent years. NAFLD is characterized by the accumulation of lipid species in hepatocytes, leading to liver inflammation that can progress to steatohepatitis, fibrosis, and cirrhosis. Risk factors contributing to NAFLD encompass genetic variations and metabolic disorders such as obesity, diabetes, and insulin resistance. Moreover, transgenerational influences, resulting in an imbalance of gut microbial composition, epigenetic modifications, and dysregulated hepatic immune responses in offspring, play a pivotal role in pediatric NAFLD development. Maternal nutrition shapes the profile of microbiota-derived metabolites in offspring, exerting significant influence on immune system regulation and the development of metabolic syndrome in offspring. In this review, we summarize recent evidence elucidating the intricate interplay between gut microbiota, epigenetics, and immunity in fetuses exposed to maternal nutrition, and its impact on the onset of NAFLD in offspring. Furthermore, potential therapeutic strategies targeting this network are also discussed.
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Affiliation(s)
- Hong-Tai Tzeng
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;
| | - Wei-Chia Lee
- Division of Urology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 33332, Taiwan
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Wang H, Qiao C, Gao Y, Geng Y, Niu F, Yang R, Wang Z, Jiang W, Sun H. The adverse effects of developmental exposure to polystyrene nanoparticles on cognitive function in weaning rats and the protective role of trihydroxy phenolacetone. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 347:123632. [PMID: 38460594 DOI: 10.1016/j.envpol.2024.123632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 02/08/2024] [Accepted: 02/20/2024] [Indexed: 03/11/2024]
Abstract
Polystyrene nanoplastic(PS-NP) can originate from sources such as plastic waste and industrial wastewater and have been shown to have deleterious effects on abnormal neurobehaviors. However, evidence regarding the health impacts, biological mechanisms, and treatment strategies underlying developmental exposure to low dose PS-NP is still lacking. This study aimed to fill this knowledge gap by administering low doses of PS-NP(50 and 100 μg/L) to weaning rats for 4 consecutive weeks. Behavioral and morphological experiments were performed to evaluate hippocampal damage, and transcriptomics and Assay for Transposase Accessible Chromatin with hight-throughput sequencing(ATAC) analyses were conducted to identify potential key targets. Additionally, Connectivity Map(CMap) database, Limited proteolysis-mass spectrometry(LiP-SMap), and molecular-protein docking were used to examine potential phytochemicals with therapeutic effects on key targets. The results indicated that developmental exposure to PS-NP can induce hippocampal impairment and aberrant neurobehaviors in adulthood. Multi-omics analyses consistently showed that apoptosis-related signaling pathways were sensitive to PS-NP exposure, and mitogen-activated protein kinase 3(Mapk3) was identified as the core gene by the gene network, which was further validated in vitro experiments. The CMap database provided a series of phytochemicals that might regulate Mapk3 expression, and trihydroxy-phenolacetone(THP) was found to have directly binding sites with Mapk3 through LiP-SMap and molecular docking analysis. Furthermore, THP administration could significantly alleviate apoptosis induced by PS-NP exposure in primary hippocampal cells through down-regulation of Mapk3. These findings suggested that developmental exposure to PS-NP has adverse effects on cognitive function and that THP can alleviate these effects by directly binding to Mapk3.
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Affiliation(s)
- Hang Wang
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China; National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, 150081, China
| | - Conghui Qiao
- National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, 150081, China
| | - Yang Gao
- Cosmetics Technology Center, Chinese Academy of Inspection and Quarantine, No.11 Rong Hua South Road, Economic-Technological Development Area, Beijing, 100176, China
| | - Yiding Geng
- National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, 150081, China
| | - Fengru Niu
- National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, 150081, China
| | - Ruiming Yang
- National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, 150081, China
| | - Zheng Wang
- National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, 150081, China
| | - Wenbo Jiang
- National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, 150081, China; Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hongru Sun
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China.
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Li L, Sun L, Liang X, Ou Q, Tan X, Li F, Lai Z, Ding C, Chen H, Yu X, Wu Q, Wei J, Wu F, Wang L. Maternal betaine supplementation ameliorates fatty liver disease in offspring mice by inhibiting hepatic NLRP3 inflammasome activation. Nutr Res Pract 2023; 17:1084-1098. [PMID: 38053832 PMCID: PMC10694418 DOI: 10.4162/nrp.2023.17.6.1084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 07/26/2023] [Accepted: 08/14/2023] [Indexed: 12/07/2023] Open
Abstract
BACKGROUND/OBJECTIVES Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. MATERIALS/METHODS Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.
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Affiliation(s)
- Lun Li
- Department of Delivery Room, Guangzhou Women and Children’s Medical Center, Guangzhou 510623, People’s Republic of China
| | - Liuqiao Sun
- Department of Maternal, Child and Adolescent Health, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Xiaoping Liang
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Qian Ou
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Xuying Tan
- Department of Child Health Care, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, People’s Republic of China
| | - Fangyuan Li
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Zhiwei Lai
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Chenghe Ding
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Hangjun Chen
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Xinxue Yu
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Qiongmei Wu
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Jun Wei
- Department of Science and Technology, Guangzhou Customs, Guangzhou 510623, People’s Republic of China
| | - Feng Wu
- Department of Science and Technology, Guangzhou Customs, Guangzhou 510623, People’s Republic of China
| | - Lijun Wang
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China
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La Colla A, Cámara CA, Campisano S, Chisari AN. Mitochondrial dysfunction and epigenetics underlying the link between early-life nutrition and non-alcoholic fatty liver disease. Nutr Res Rev 2023; 36:281-294. [PMID: 35067233 DOI: 10.1017/s0954422422000038] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Early-life malnutrition plays a critical role in foetal development and predisposes to metabolic diseases later in life, according to the concept of 'developmental programming'. Different types of early nutritional imbalance, including undernutrition, overnutrition and micronutrient deficiency, have been related to long-term metabolic disorders. Accumulating evidence has demonstrated that disturbances in nutrition during the period of preconception, pregnancy and primary infancy can affect mitochondrial function and epigenetic mechanisms. Moreover, even though multiple mechanisms underlying non-alcoholic fatty liver disease (NAFLD) have been described, in the past years, special attention has been given to mitochondrial dysfunction and epigenetic alterations. Mitochondria play a key role in cellular metabolic functions. Dysfunctional mitochondria contribute to oxidative stress, insulin resistance and inflammation. Epigenetic mechanisms have been related to alterations in genes involved in lipid metabolism, fibrogenesis, inflammation and tumorigenesis. In accordance, studies have reported that mitochondrial dysfunction and epigenetics linked to early-life nutrition can be important contributing factors in the pathogenesis of NAFLD. In this review, we summarise the current understanding of the interplay between mitochondrial dysfunction, epigenetics and nutrition during early life, which is relevant to developmental programming of NAFLD.
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Affiliation(s)
- Anabela La Colla
- Departamento de Química y Bioquímica, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, 7600 Mar del Plata, Argentina
| | - Carolina Anahí Cámara
- Departamento de Química y Bioquímica, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, 7600 Mar del Plata, Argentina
| | - Sabrina Campisano
- Departamento de Química y Bioquímica, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, 7600 Mar del Plata, Argentina
| | - Andrea Nancy Chisari
- Departamento de Química y Bioquímica, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, 7600 Mar del Plata, Argentina
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Cao X, Zolnikova O, Maslennikov R, Reshetova M, Poluektova E, Bogacheva A, Zharkova M, Ivashkin V. Low Short-Chain-Fatty-Acid-Producing Activity of the Gut Microbiota Is Associated with Hypercholesterolemia and Liver Fibrosis in Patients with Metabolic-Associated (Non-Alcoholic) Fatty Liver Disease. GASTROINTESTINAL DISORDERS 2023; 5:464-473. [DOI: 10.3390/gidisord5040038] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/26/2024] Open
Abstract
The aim of this study was to investigate the short-chain fatty acid (SCFA) activity of the gut microbiota of patients with metabolic-associated fatty liver disease (MAFLD). The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas–liquid chromatography. Liver fibrosis was assessed using the FIB-4 index and elastography. Among 42 non-cirrhotic MAFLD patients, 24 had high fecal SCFA levels (group H) and 18 had low fecal SCFA levels (group L). Patients in group H had lower serum uric acid, total cholesterol, and LDL cholesterol levels but a higher BMI than those in group L. All patients in group L and only 37.9% of those in group H were found to have hypercholesterolemia. In patients with hypercholesterolemia, the level of SCFAs was lower than that in patients without hypercholesterolemia. Patients in group H had less liver fibrosis than patients in group L. A total of 50.0% of the patients in group H and 92.3% of those in group L had significant liver fibrosis (≥F2). Patients with significant liver fibrosis had lower levels of fecal SCFAs—particularly acetate and butyrate. The fecal SCFA levels were positively correlated with gamma-glutamyl transferase, total bilirubin levels, BMI, and platelet count and were negatively correlated with FIB-4, liver stiffness, serum total, and LDL cholesterol levels.
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Affiliation(s)
- Xinlu Cao
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Oksana Zolnikova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119121, Russia
| | - Maria Reshetova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119121, Russia
| | - Arina Bogacheva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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10
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Myint M, Oppedisano F, De Giorgi V, Kim BM, Marincola FM, Alter HJ, Nesci S. Inflammatory signaling in NASH driven by hepatocyte mitochondrial dysfunctions. J Transl Med 2023; 21:757. [PMID: 37884933 PMCID: PMC10605416 DOI: 10.1186/s12967-023-04627-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 10/14/2023] [Indexed: 10/28/2023] Open
Abstract
Liver steatosis, inflammation, and variable degrees of fibrosis are the pathological manifestations of nonalcoholic steatohepatitis (NASH), an aggressive presentation of the most prevalent chronic liver disease in the Western world known as nonalcoholic fatty liver (NAFL). Mitochondrial hepatocyte dysfunction is a primary event that triggers inflammation, affecting Kupffer and hepatic stellate cell behaviour. Here, we consider the role of impaired mitochondrial function caused by lipotoxicity during oxidative stress in hepatocytes. Dysfunction in oxidative phosphorylation and mitochondrial ROS production cause the release of damage-associated molecular patterns from dying hepatocytes, leading to activation of innate immunity and trans-differentiation of hepatic stellate cells, thereby driving fibrosis in NASH.
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Affiliation(s)
| | - Francesca Oppedisano
- Department of Health Sciences, Institute of Research for Food Safety and Health, University "Magna Græcia" of Catanzaro, Catanzaro, Italy
| | - Valeria De Giorgi
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, USA
| | | | | | - Harvey J Alter
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, USA
| | - Salvatore Nesci
- Department of Veterinary Medical Sciences, University of Bologna, Ozzano Emilia, Italy.
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11
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Ooi KS, Abdul Jalal MI, Wong JY, Choo MY, Kamruldzaman NA, Lye CW, Lum LCS. The Prevalence and Determinants of Child Hunger and Its Associations with Early Childhood Nutritional Status among Urban Poverty Households during COVID-19 Pandemic in Petaling District, Malaysia: An Exploratory Cross-Sectional Survey. Nutrients 2023; 15:2356. [PMID: 37242239 PMCID: PMC10222894 DOI: 10.3390/nu15102356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/24/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
Child hunger was prevalent during the COVID-19 pandemic, but the extent, determinants, and impact on pre-school children aged 6 months to 7 years old from Malaysian urban poor households are still unknown. This exploratory cross-sectional study was performed between July 2020 and January 2021 at the Lembah Subang People Housing Project, Petaling. The households' food security status was assessed using the previously validated Radimer/Cornell questionnaire, and the children's anthropometric measurements were taken. Food diversity score was assessed using the World Health Organization Infant and Young Children Feeding (under-2 children) or Food and Agriculture Organization Women's Dietary Diversity (2-year-old-and-above children) systems. Overall, 106 households were recruited. The prevalence of child hunger is 58.4% (95% CI: 50.0, 67.4). Significant differences were found in breastfeeding and sugar-sweetened beverage consumption between under-2 and ≥2-year-old children. There were no significant differences between child hunger and other food-insecure groups in weight-for-age, height-for-age, and weight-for-height z-scores. Only a higher dietary diversity score was significantly protective against child hunger after adjusting for maternal age, paternal employment status, and the number of household children (ORadjusted: 0.637 (95% CI: 0.443, 0.916), p = 0.015)). Proactive strategies are warranted to reduce child hunger during the COVID-19 pandemic by improving childhood dietary diversity.
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Affiliation(s)
- Kai Shen Ooi
- Department of Paediatrics, University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia
| | - Muhammad Irfan Abdul Jalal
- UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | - Jing Yuan Wong
- Department of Paediatrics, University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia
| | - Minn Yin Choo
- Department of Paediatrics, University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia
| | | | - Chuan Way Lye
- Department of Public Health, University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia
| | - Lucy Chai See Lum
- Department of Paediatrics, University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia
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12
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Jiang T, Xiao H, Li B, He H, Wang H, Chen L. LOX overexpression programming mediates the osteoclast mechanism of low peak bone mass in female offspring rats caused by pregnant dexamethasone exposure. Cell Commun Signal 2023; 21:84. [PMID: 37095518 PMCID: PMC10124047 DOI: 10.1186/s12964-023-01115-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 03/25/2023] [Indexed: 04/26/2023] Open
Abstract
BACKGROUND Osteoporosis is a degenerative disease characterized by reduced bone mass, with low peak bone mass being the predominant manifestation during development and having an intrauterine origin. Pregnant women at risk of preterm delivery are commonly treated with dexamethasone to promote fetal lung development. However, pregnant dexamethasone exposure (PDE) can lead to reduced peak bone mass and susceptibility to osteoporosis in offspring. In this study, we aimed to investigate the mechanism of PDE-induced low peak bone mass in female offspring from the perspective of altered osteoclast developmental programming. METHODS 0.2 mg/kg.d dexamethasone was injected subcutaneously into rats on gestation days (GDs) 9-20. Some pregnant rats were killed at GD20 to remove fetal rat long bones, the rest were delivered naturally, and some adult offspring rats were given ice water swimming stimulation for two weeks. RESULTS The results showed that the fetal rat osteoclast development was inhibited in the PDE group compared with the control group. In contrast, the adult rat osteoclast function was hyperactivation with reduced peak bone mass. We further found that the promoter region methylation levels of lysyl oxidase (LOX) were decreased, the expression was increased, and the production of reactive oxygen species (ROS) was raised in PDE offspring rat long bone before and after birth. Combined in vivo and in vitro experiments, we confirmed that intrauterine dexamethasone promoted the expression and binding of the glucocorticoid receptor (GR) and estrogen receptor β (ERβ) in osteoclasts and mediated the decrease of LOX methylation level and increase of expression through upregulation of 10-11 translocator protein 3 (Tet3). CONCLUSIONS Taken together, we confirm that dexamethasone causes osteoclast LOX hypomethylation and high expression through the GR/ERβ/Tet3 pathway, leading to elevated ROS production and that this intrauterine epigenetic programming effect can be carried over to postnatal mediating hyperactivation in osteoclast and reduced peak bone mass in adult offspring. This study provides an experimental basis for elucidating the mechanism of osteoclast-mediated intrauterine programming of low peak bone mass in female offspring of PDE and for exploring its early targets for prevention and treatment. Video Abstract.
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Affiliation(s)
- Tao Jiang
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Hao Xiao
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Bin Li
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Hangyuan He
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Hui Wang
- Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China.
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China.
| | - Liaobin Chen
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China.
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13
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Yuan P, Xu H, Ma Y, Niu J, Liu Y, Huang L, Jiang S, Jiao N, Yuan X, Yang W, Li Y. Effects of dietary Galla Chinensis tannin supplementation on immune function and liver health in broiler chickens challenged with lipopolysaccharide. Front Vet Sci 2023; 10:1126911. [PMID: 36865438 PMCID: PMC9974168 DOI: 10.3389/fvets.2023.1126911] [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: 12/18/2022] [Accepted: 01/30/2023] [Indexed: 02/16/2023] Open
Abstract
Herein, Galla Chinensis tannin (GCT) was examined for its influence on preventing lipopolysaccharide (LPS)-induced liver damage in broiler chickens. Approximately 486 one-day-old healthy broilers were randomly allocated to 3 treatment groups (control, LPS, and LPS + GCT). The control and LPS groups were fed a basal diet and the LPS+GCT group was fed the basal diet supplemented with 300 mg/kg GCT. LPS was intraperitoneally injected (1 mg/kg body weight BW) in broilers in the LPS and LPS+GCT groups at 17, 19, and 21 days of age. The results manifested that dietary GCT addition attenuated LPS-induced deleterious effects on serum parameters and significantly increased serum immunoglobulin and complement C3 concentrations relative to the control and LPS groups. Dietary supplementation of GCT inhibited LPS-induced increase in broiler hepatic inflammatory cytokines, caspases activities, and TLR4/NF-κB pathway-related gene mRNA expression. Therefore, 300 mg/kg GCT addition to the diet improved the immune function of broilers and inhibit liver inflammation by blocking the TLR4/NF-κB pathway. Our findings provide support for the application of GCT in poultry production.
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Affiliation(s)
- Peng Yuan
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China
| | - Haitao Xu
- Animal Husbandry Development Center of Changyi City, Weifang, China
| | - Yuanfei Ma
- Agricultural and Rural Comprehensive Service Center of Bincheng District, Binzhou, China
| | - Jiaxing Niu
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China
| | - Yang Liu
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China
| | - Libo Huang
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China
| | - Shuzhen Jiang
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China
| | - Ning Jiao
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China
| | - Xuejun Yuan
- College of Life Sciences, Shandong Agricultural University, Tai'an, China
| | - Weiren Yang
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China,*Correspondence: Weiren Yang ✉
| | - Yang Li
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China,Yang Li ✉
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14
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Gutiérrez-Cuevas J, Lucano-Landeros S, López-Cifuentes D, Santos A, Armendariz-Borunda J. Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies. Cancers (Basel) 2022; 15:23. [PMID: 36612019 PMCID: PMC9818030 DOI: 10.3390/cancers15010023] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the sixth most frequent cancer in the world, being the third cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH) is characterized by fatty infiltration, oxidative stress and necroinflammation of the liver, with or without fibrosis, which can progress to advanced liver fibrosis, cirrhosis and HCC. Obesity, metabolic syndrome, insulin resistance, and diabetes exacerbates the course of NASH, which elevate the risk of HCC. The growing prevalence of obesity are related with increasing incidence of NASH, which may play a growing role in HCC epidemiology worldwide. In addition, HCC initiation and progression is driven by reprogramming of metabolism, which indicates growing appreciation of metabolism in the pathogenesis of this disease. Although no specific preventive pharmacological treatments have recommended for NASH, dietary restriction and exercise are recommended. This review focuses on the molecular connections between HCC and NASH, including genetic and risk factors, highlighting the metabolic reprogramming and aberrant epigenetic alterations in the development of HCC in NASH. Current therapeutic aspects of NASH/HCC are also reviewed.
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Affiliation(s)
- Jorge Gutiérrez-Cuevas
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
| | - Silvia Lucano-Landeros
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
| | - Daniel López-Cifuentes
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
| | - Arturo Santos
- Tecnologico de Monterrey, EMCS, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico
| | - Juan Armendariz-Borunda
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
- Tecnologico de Monterrey, EMCS, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico
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15
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Tourkochristou E, Assimakopoulos SF, Thomopoulos K, Marangos M, Triantos C. NAFLD and HBV interplay - related mechanisms underlying liver disease progression. Front Immunol 2022; 13:965548. [PMID: 36544761 PMCID: PMC9760931 DOI: 10.3389/fimmu.2022.965548] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 11/15/2022] [Indexed: 12/08/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and Hepatitis B virus infection (HBV) constitute common chronic liver diseases with worldwide distribution. NAFLD burden is expected to grow in the coming decade, especially in western countries, considering the increased incidence of diabetes and obesity. Despite the organized HBV vaccinations and use of anti-viral therapies globally, HBV infection remains endemic and challenging public health issue. As both NAFLD and HBV have been associated with the development of progressive fibrosis, cirrhosis and hepatocellular carcinoma (HCC), the co-occurrence of both diseases has gained great research and clinical interest. The causative relationship between NAFLD and HBV infection has not been elucidated so far. Dysregulated fatty acid metabolism and lipotoxicity in NAFLD disease seems to initiate activation of signaling pathways that enhance pro-inflammatory responses and disrupt hepatocyte cell homeostasis, promoting progression of NAFLD disease to NASH, fibrosis and HCC and can affect HBV replication and immune encountering of HBV virus, which may further have impact on liver disease progression. Chronic HBV infection is suggested to have an influence on metabolic changes, which could lead to NAFLD development and the HBV-induced inflammatory responses and molecular pathways may constitute an aggravating factor in hepatic steatosis development. The observed altered immune homeostasis in both HBV infection and NAFLD could be associated with progression to HCC development. Elucidation of the possible mechanisms beyond HBV chronic infection and NAFLD diseases, which could lead to advanced liver disease or increase the risk for severe complications, in the case of HBV-NAFLD co-existence is of high clinical significance in the context of designing effective therapeutic targets.
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Affiliation(s)
- Evanthia Tourkochristou
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Stelios F. Assimakopoulos
- Division of Infectious Diseases, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Markos Marangos
- Division of Infectious Diseases, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
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16
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Hong Y, Zhang Y, Zhao H, Chen H, Yu QQ, Cui H. The roles of lncRNA functions and regulatory mechanisms in the diagnosis and treatment of hepatocellular carcinoma. Front Cell Dev Biol 2022; 10:1051306. [PMID: 36467404 PMCID: PMC9716033 DOI: 10.3389/fcell.2022.1051306] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 11/07/2022] [Indexed: 10/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent and deadly type of liver cancer. While the underlying molecular mechanisms are poorly understood, it is documented that lncRNAs may play key roles. Many HCC-associated lncRNAs have been linked to HBV and HCV infection, mediating gene expression, cell growth, development, and death. Studying the regulatory mechanisms and biological functions of HCC-related lncRNAs will assist our understanding of HCC pathogenesis as well as its diagnosis and management. Here, we address the potential of dysregulated lncRNAs in HCC as diagnostic and therapeutic biomarkers, and we evaluate the oncogenic or tumor-suppressive properties of these lncRNAs.
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Affiliation(s)
- Yuling Hong
- School of Clinical Medicine, Jining Medical University, Jining, China
| | - Yunxing Zhang
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Haibo Zhao
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Hailing Chen
- School of Clinical Medicine, Jining Medical University, Jining, China
| | - Qing-Qing Yu
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Hongxia Cui
- Jining First People’s Hospital, Jining Medical College, Jining, China
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17
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Di Gesù CM, Matz LM, Bolding IJ, Fultz R, Hoffman KL, Marino Gammazza A, Petrosino JF, Buffington SA. Maternal gut microbiota mediate intergenerational effects of high-fat diet on descendant social behavior. Cell Rep 2022; 41:111461. [PMID: 36223744 PMCID: PMC9597666 DOI: 10.1016/j.celrep.2022.111461] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/03/2022] [Accepted: 09/15/2022] [Indexed: 12/11/2022] Open
Abstract
Dysbiosis of the maternal gut microbiome during pregnancy is associated with adverse neurodevelopmental outcomes. We previously showed that maternal high-fat diet (MHFD) in mice induces gut dysbiosis, social dysfunction, and underlying synaptic plasticity deficits in male offspring (F1). Here, we reason that, if HFD-mediated changes in maternal gut microbiota drive offspring social deficits, then MHFD-induced dysbiosis in F1 female MHFD offspring would likewise impair F2 social behavior. Metataxonomic sequencing reveals reduced microbial richness among female F1 MHFD offspring. Despite recovery of microbial richness among MHFD-descendant F2 mice, they display social dysfunction. Post-weaning Limosilactobacillus reuteri treatment increases the abundance of short-chain fatty acid-producing taxa and rescues MHFD-descendant F2 social deficits. L. reuteri exerts a sexually dimorphic impact on gut microbiota configuration, increasing discriminant taxa between female cohorts. Collectively, these results show multigenerational impacts of HFD-induced dysbiosis in the maternal lineage and highlight the potential of maternal microbiome-targeted interventions for neurodevelopmental disorders.
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Affiliation(s)
- Claudia M. Di Gesù
- Department of Neurobiology, The University of Texas Medical Branch, Galveston, TX 77555, USA,Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy,Current address: Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston,These authors contributed equally
| | - Lisa M. Matz
- Department of Neurobiology, The University of Texas Medical Branch, Galveston, TX 77555, USA,These authors contributed equally
| | - Ian J. Bolding
- Department of Neurobiology, The University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Robert Fultz
- Department of Neurobiology, The University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Kristi L. Hoffman
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA,Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Antonella Marino Gammazza
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
| | - Joseph F. Petrosino
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA,Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Shelly A. Buffington
- Department of Neurobiology, The University of Texas Medical Branch, Galveston, TX 77555, USA,Sealy Center for Microbiome Research, The University of Texas Medical Branch, Galveston, TX 77555, USA,Lead contact,Correspondence:
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18
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Sun D, Li C, Chen S, Zhang X. Emerging Role of Dendritic Cell Intervention in the Treatment of Inflammatory Bowel Disease. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7025634. [PMID: 36262975 PMCID: PMC9576373 DOI: 10.1155/2022/7025634] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 09/27/2022] [Indexed: 11/17/2022]
Abstract
Dendritic cells (DCs) are the most important antigen-presenting cells and are pivotal in initiating effective adaptive immune responses to induce immune tolerance and maintain immune homeostasis. Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is chronic, intestinal inflammatory and autoimmune disorder. DCs participate in IBD pathogenesis. This review is aimed at briefly discussing the role of DCs in IBD and the relationship between them and highlighting the prominent role of these cells in the treatment of these disorders.
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Affiliation(s)
- Donglei Sun
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China
| | - Chenyang Li
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China
| | - Shuang Chen
- Department of Pediatrics and Department of Biomedical Science, Cedars Sinai Medical Center, Los Angeles, USA
| | - Xiaolan Zhang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China
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19
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Diagnostic and Molecular Portraits of Microbiome and Metabolomics of Short-Chain Fatty Acids and Bile acids in Liver Disease. Process Biochem 2022. [DOI: 10.1016/j.procbio.2022.10.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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20
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Non-Coding RNAs in Hepatocellular Carcinoma. LIVERS 2022. [DOI: 10.3390/livers2030017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Liver cancer ranks as the fourth leading cause of cancer-related deaths. Despite extensive research efforts aiming to evaluate the biological mechanisms underlying hepatocellular carcinoma (HCC) development, little has been translated towards new diagnostic and treatment options for HCC patients. Historically, the focus has been centered on coding RNAs and their respective proteins. However, significant advances in sequencing and RNA detection technologies have shifted the research focus towards non-coding RNAs (ncRNA), as well as their impact on HCC development and progression. A number of studies reported complex post-transcriptional interactions between various ncRNA and coding RNA molecules. These interactions offer insights into the role of ncRNAs in both the known pathways leading to oncogenesis, such as dysregulation of p53, and lesser-known mechanisms, such as small nucleolar RNA methylation. Studies investigating these mechanisms have identified prevalent ncRNA changes in microRNAs, snoRNAs, and long non-coding RNAs that can both pre- and post-translationally regulate key factors in HCC progression. In this review, we present relevant publications describing ncRNAs to summarize the impact of different ncRNA species on liver cancer development and progression and to evaluate recent attempts at clinical translation.
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21
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Therapeutic Potential of Human Microbiome-Based Short-Chain Fatty Acids and Bile Acids in Liver Disease. LIVERS 2022. [DOI: 10.3390/livers2030012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Microbiome-derived short chain fatty acids (SCFAs: acetate, propionate, and butyrate) and bile acids (BAs: primary BAs and secondary BAs) widely influence liver metabolic inflammation, immune responses, and carcinogenesis. In recent literature, the role of SCFAs and BAs in various liver diseases has been discussed. SCFAs and BAs are two types of microbiome-derived metabolites and they have been shown to have immunoregulatory ability in autoimmunity, inflammation, and liver-cancer microcellular environments. SCFAs and BAs are dependent on dietary components. The numerous regulatory processes in lymphocytes and non-immune cells that underpin both the positive and harmful effects of microbial metabolites include variations in metabolic signaling and epigenetic states. As a result, histone deacetylase (HDAC) inhibitors, SCFAs, and BAs, which are powerful immunometabolism modulators, have been explored. BAs have also been shown to alter the microbiome as well as adaptive and innate immune systems. We therefore emphasize the important metabolites in liver disease for clinical therapeutic applications. A deep understanding of SCFAs and Bas, as well as their molecular risk, could reveal more about certain liver-disease conditions.
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22
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Bao S, Wang X, Ma Q, Wei C, Nan J, Ao W. Mongolian medicine in treating type 2 diabetes mellitus combined with nonalcoholic fatty liver disease via FXR/LXR-mediated P2X7R/NLRP3/NF-κB pathway activation. CHINESE HERBAL MEDICINES 2022; 14:367-375. [PMID: 36118003 PMCID: PMC9476729 DOI: 10.1016/j.chmed.2022.06.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 02/17/2022] [Accepted: 06/15/2022] [Indexed: 11/20/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are the most problematic metabolic diseases in the world. NAFLD encompasses a spectrum of severity, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis, increasing the risk of cirrhosis and hepatocellular carcinoma. Importantly, NAFLD is closely linked to obesity and tightly interrelated with insulin resistance and T2DM. T2DM and NAFLD (T2DM-NAFLD) are called as the Xike Rixijing Disease and Tonglaga Indigestion Disease respectively, in Mongolian medicine. Xike Rixijing Disease maybe develop into Tonglaga Indigestion Disease. Forturnately many Mongolian medicines show efficient treatment of T2DM-NAFLD, such as Agriophyllum squarrosum, Haliyasu (dried powder of camel placenta), Digeda-4 (herbs of Lomatogonium carinthiacum, rhizomata of Coptis chinensis, ripe fruits of Gardenia jasminoides, herbs of Dianthus superbus), Guangmingyan Siwei Decoction Powder (Halite, ripe fruits of Terminalia chebula, rhizomata of Zingiber officinale, fruit clusters of Piper longum), Tonglaga-5 (ripe fruits of Punica granatum, barks of Cinnamomum cassia, ripe fruits of Amomum kravanh, fruit clusters of Piper longum, flowers of Carthamus tinctorius), Tegexidegeqi (rhizomata of Inula helenium, ripe fruits of Gardenia jasminoides, rhizomata of Platycodon grandiflorum, rhizomata of Coptis chinensis, heartwood of Caesalpinia sappan), Ligan Shiliu Bawei San (ripe fruits of Punica granatum, barks of Cinnamomum cassia, ripe fruits of Amomum kravanh, fruit clusters of Piper longum, flowers of Carthamus tinctorius, ripe fruits of Amomum tsao-ko, rhizomata of Zingiber officinale), etc. Principles of Mongolian medicine in treating diseases: by balancing “three essences or roots” and “seven elements”, strengthening liver and kidney function, transporting nutrients to enhance physical strength and disease resistance, and combined with drugs for comprehensive conditioning treatment. However, their molecular mechanisms remain unclear. In this review, we prospect that Mongolian medicines might be a promising treatment for T2DM-NAFLD by activating P2X7R/NLRP3/NF-κB inflammatory pathway via lipid-sensitive nuclear receptors (i.e., FXR and LXR).
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Affiliation(s)
- Shuyin Bao
- Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao 028000, China
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao 028000, China
- Jilin Key Laboratory for Traditional Chinese Korean Medicine, College of Pharmacy, Yanbian University, Yanji 133002, China
| | - Xiuzhi Wang
- Department of Medicines and Foods, Tongliao Vocational College, Tongliao 028000, China
| | - Qianqian Ma
- Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao 028000, China
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao 028000, China
| | - Chengxi Wei
- Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao 028000, China
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao 028000, China
- Corresponding authors.
| | - Jixing Nan
- Jilin Key Laboratory for Traditional Chinese Korean Medicine, College of Pharmacy, Yanbian University, Yanji 133002, China
- Corresponding authors.
| | - Wuliji Ao
- Research and development center, Inner Mongolia Research Institute of Traditional Mongolian Medicine Engineering Technology, Tongliao 028000, China
- Mongolian Medicine R&D National Local Union Engineering Research Center, Inner Mongolia Minzu University, Tongliao 028000, China
- Corresponding authors.
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23
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Ajah AA, Lembede BW, Nkomozepi P, Erlwanger KH, Nyakudya TT. Neonatal Oral Administration of Chrysin Prevents Long-Term Development of Non-Alcoholic Fatty Liver Disease in a Sexually Dimorphic Manner in Fructose Nurtured Sprague Dawley Rats. Life (Basel) 2022; 12:life12060790. [PMID: 35743821 PMCID: PMC9225280 DOI: 10.3390/life12060790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/30/2022] [Accepted: 05/23/2022] [Indexed: 12/03/2022] Open
Abstract
High-fructose diets are linked with the development of non-alcoholic fatty liver disease (NAFLD), the management of which is a burden to society. Interventions with phytochemicals in the early postnatal period may prevent fructose-induced NAFLD later in adulthood. We investigated the protective potential of chrysin against fructose-induced NAFLD. Four-day-old male and female suckling Sprague Dawley rats (N = 112) were randomly grouped and orally gavaged daily with distilled water (negative Control-Cn + W), chrysin(Chr-100 mg/kg), fructose-solution (Fr-20% w/v), and Chr + Fr between postnatal day (PND) 4 and 21 and then weaned onto normal rat chow and plain drinking water to PND 55. From PND 56 to 130, half of the rats continued on plain water, and the rest had Fr as drinking fluid. Terminally, the liver tissue was collected, and the lipid content was determined and histologically assessed for NAFLD. Dietary Fr induced an increased hepatic lipid content (p = 0.0001 vs. Cn + W) both sexes, and it was only attenuated by neonatal Chr in female rats (p < 0.05). Histologically, there was increased microvesicular steatosis (p = 0.0001 vs. Cn + W) in both sexes, and it was prevented by neonatal Chr (p > 0.05). Fr caused macrovesicular steatosis (p = 0.01 vs. Cn + W) in females only, and chrysin did not prevent it (p > 0.05). Fr induced hepatocellular hypertrophy, and inflammation was observed in females only (p = 0.01 vs. Cn + W), and this was prevented by Chr (p > 0.05). The collagen area fraction was increased by Fr (p = 0.02 (males) and p = 0.04 (females) vs. Cn + W, respectively; however, chrysin did not prevent this (p > 0.05). Neonatal chrysin prevented some of the deleterious effects of the high-fructose diet on the liver, suggesting that chrysin should be further explored as a strategic prophylactic neonatal intervention against high-fructose-diet-induced NAFLD.
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Affiliation(s)
- Austin A. Ajah
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa; (B.W.L.); (K.H.E.)
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, University of Port Harcourt, P.M.B. 5323, Choba, Port Harcourt 500102, Nigeria
- Correspondence:
| | - Busisani W. Lembede
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa; (B.W.L.); (K.H.E.)
| | - Pilani Nkomozepi
- Department of Human Anatomy and Physiology, Faculty of Health Sciences, University of Johannesburg, Corner Beit and Siemert Street, Doornfontein, Johannesburg 2094, South Africa; (P.N.); (T.T.N.)
| | - Kennedy H. Erlwanger
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa; (B.W.L.); (K.H.E.)
| | - Trevor T. Nyakudya
- Department of Human Anatomy and Physiology, Faculty of Health Sciences, University of Johannesburg, Corner Beit and Siemert Street, Doornfontein, Johannesburg 2094, South Africa; (P.N.); (T.T.N.)
- Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Gezina, Pretoria 0031, South Africa
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24
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Intestinal Microbiota-Derived Short Chain Fatty Acids in Host Health and Disease. Nutrients 2022; 14:nu14091977. [PMID: 35565943 PMCID: PMC9105144 DOI: 10.3390/nu14091977] [Citation(s) in RCA: 103] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 05/01/2022] [Accepted: 05/06/2022] [Indexed: 01/27/2023] Open
Abstract
Intestinal microbiota has its role as an important component of human physiology. It produces metabolites that module key functions to establish a symbiotic crosstalk with their host. Among them, short chain fatty acids (SCFAs), produced by intestinal bacteria during the fermentation of partially and non-digestible polysaccharides, play key roles in regulating colon physiology and changing intestinal environment. Recent research has found that SCFAs not only influence the signal transduction pathway in the gut, but they also reach tissues and organs outside of the gut, through their circulation in the blood. Growing evidence highlights the importance of SCFAs level in influencing health maintenance and disease development. SCFAs are probably involved in the management of host health in a complicated (positive or negative) way. Here, we review the current understanding of SCFAs effects on host physiology and discuss the potential prevention and therapeutics of SCFAs in a variety of disorders. It provides a systematic theoretical basis for the study of mechanisms and precise intake level of SCFAs to promote human health.
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25
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Valentini F, Rocchi G, Vespasiani-Gentilucci U, Guarino MPL, Altomare A, Carotti S. The Origins of NAFLD: The Potential Implication of Intrauterine Life and Early Postnatal Period. Cells 2022; 11:562. [PMID: 35159371 PMCID: PMC8834011 DOI: 10.3390/cells11030562] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 01/30/2022] [Accepted: 02/02/2022] [Indexed: 02/04/2023] Open
Abstract
Fetal life and the first few months after birth represent a plastic age, defined as a "window of opportunity", as the organism is particularly susceptible to environmental pressures and has to adapt to environmental conditions. Several perturbations in pregnancy, such as excessive weight gain, obesity, gestational diabetes mellitus and an inadequate or high-fat diet, have been associated with long-term metabolic consequences in offspring, even without affecting birth weight. Moreover, great interest has also been focused on the relationship between the gut microbiome of early infants and health status in later life. Consistently, in various epidemiological studies, a condition of dysbiosis has been associated with an increased inflammatory response and metabolic alterations in the host, with important consequences on the intestinal and systemic health of the unborn child. This review aims to summarize the current knowledge on the origins of NAFLD, with particular attention to the potential implications of intrauterine life and the early postnatal period. Due to the well-known association between gut microbiota and the risk of NAFLD, a specific focus will be devoted to factors affecting early microbiota formation/composition.
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Affiliation(s)
- Francesco Valentini
- Pediatric Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology, “Sapienza” University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy;
| | - Giulia Rocchi
- Unit of Food Science and Human Nutrition, Campus Biomedico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
| | - Umberto Vespasiani-Gentilucci
- Unit of Internal Medicine and Hepatology, Fondazione Policlinico Campus Biomedico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
| | - Michele Pier Luca Guarino
- Gastroenterology Unit, Fondazione Policlinico Campus Biomedico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
| | - Annamaria Altomare
- Gastroenterology Unit, Fondazione Policlinico Campus Biomedico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
| | - Simone Carotti
- Unit of Microscopic and Ultrastructural Anatomy, Campus Biomedico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
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26
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Genetic and epigenetic processes linked to cancer. Cancer 2022. [DOI: 10.1016/b978-0-323-91904-3.00013-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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27
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Qu W, Ma T, Cai J, Zhang X, Zhang P, She Z, Wan F, Li H. Liver Fibrosis and MAFLD: From Molecular Aspects to Novel Pharmacological Strategies. Front Med (Lausanne) 2021; 8:761538. [PMID: 34746195 PMCID: PMC8568774 DOI: 10.3389/fmed.2021.761538] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 09/27/2021] [Indexed: 12/11/2022] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a new disease definition, and this nomenclature MAFLD was proposed to renovate its former name, non-alcoholic fatty liver disease (NAFLD). MAFLD/NAFLD have shared and predominate causes from nutrition overload to persistent liver damage and eventually lead to the development of liver fibrosis and cirrhosis. Unfortunately, there is an absence of effective treatments to reverse MAFLD/NAFLD-associated fibrosis. Due to the significant burden of MAFLD/NAFLD and its complications, there are active investigations on the development of novel targets and pharmacotherapeutics for treating this disease. In this review, we cover recent discoveries in new targets and molecules for antifibrotic treatment, which target pathways intertwined with the fibrogenesis process, including lipid metabolism, inflammation, cell apoptosis, oxidative stress, and extracellular matrix formation. Although marked advances have been made in the development of antifibrotic therapeutics, none of the treatments have achieved the endpoints evaluated by liver biopsy or without significant side effects in a large-scale trial. In addition to the discovery of new druggable targets and pharmacotherapeutics, personalized medication, and combinatorial therapies targeting multiple profibrotic pathways could be promising in achieving successful antifibrotic interventions in patients with MAFLD/NAFLD.
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Affiliation(s)
- Weiyi Qu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal, Wuhan University, Wuhan, China
| | - Tengfei Ma
- Institute of Model Animal, Wuhan University, Wuhan, China
- Department of Neurology, Huanggang Central Hospital, Huanggang, China
- Huanggang Institute of Translational Medicine, Huanggang Central Hospital, Huanggang, China
| | - Jingjing Cai
- Institute of Model Animal, Wuhan University, Wuhan, China
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Xiaojing Zhang
- Institute of Model Animal, Wuhan University, Wuhan, China
- School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Peng Zhang
- Institute of Model Animal, Wuhan University, Wuhan, China
- School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Zhigang She
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal, Wuhan University, Wuhan, China
| | - Feng Wan
- Department of Neurology, Huanggang Central Hospital, Huanggang, China
| | - Hongliang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal, Wuhan University, Wuhan, China
- Huanggang Institute of Translational Medicine, Huanggang Central Hospital, Huanggang, China
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28
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Liu L, Liu B, Yu J, Zhang D, Shi J, Liang P. Development of a Toll-Like Receptor-Based Gene Signature That Can Predict Prognosis, Tumor Microenvironment, and Chemotherapy Response for Hepatocellular Carcinoma. Front Mol Biosci 2021; 8:729789. [PMID: 34621787 PMCID: PMC8490642 DOI: 10.3389/fmolb.2021.729789] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 08/16/2021] [Indexed: 11/19/2022] Open
Abstract
Objective: Emerging evidence highlights the implications of the toll-like receptor (TLR) signaling pathway in the pathogenesis and therapeutic regimens of hepatocellular carcinoma (HCC). Herein, a prognostic TLR-based gene signature was conducted for HCC. Methods: HCC-specific TLRs were screened in the TCGA cohort. A LASSO model was constructed based on prognosis-related HCC-specific TLRs. The predictive efficacy, sensitivity, and independency of this signature was then evaluated and externally verified in the ICGC, GSE14520, and GSE76427 cohorts. The associations between this signature and tumor microenvironment (stromal/immune score, immune checkpoint expression, and immune cell infiltrations) and chemotherapy response were assessed in HCC specimens. The expression of TLRs in this signature was verified in HCC and normal liver tissues by Western blot. Following si-MAP2K2 transfection, colony formation and apoptosis of Huh7 and HepG2 cells were examined. Results: Herein, we identified 60 HCC-specific TLRs. A TLR-based gene signature (MAP2K2, IRAK1, RAC1, TRAF3, MAP3K7, and SPP1) was conducted for HCC prognosis. High-risk patients exhibited undesirable outcomes. ROC curves confirmed the well prediction performance of this signature. Multivariate Cox regression analysis demonstrated that the signature was an independent prognostic indicator. Also, high-risk HCC was characterized by an increased immune score, immune checkpoint expression, and immune cell infiltration. Meanwhile, high-risk patients displayed higher sensitivity to gemcitabine and cisplatin. The dysregulation of TLRs in the signature was confirmed in HCC. MAP2K2 knockdown weakened colony formation and elevated apoptosis of Huh7 and HepG2 cells. Conclusion: Collectively, this TLR-based gene signature might assist clinicians to select personalized therapy programs for HCC patients.
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Affiliation(s)
- Lixia Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.,Department of Ultrasound, Affiliated Hospital of Hebei University, Baoding, China
| | - Bin Liu
- Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Institute of Life Science and Green Development, Hebei University, Baoding, China
| | - Jie Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China
| | - Dongyun Zhang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China
| | - Jianhong Shi
- Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Institute of Life Science and Green Development, Hebei University, Baoding, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China
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29
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Naja F, Ayoub J, Baydoun S, Nassour S, Zgheib P, Nasreddine L. Development of national dietary and lifestyle guidelines for pregnant women in Lebanon. MATERNAL & CHILD NUTRITION 2021; 17:e13199. [PMID: 33973717 PMCID: PMC8476423 DOI: 10.1111/mcn.13199] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/01/2021] [Accepted: 04/08/2021] [Indexed: 01/23/2023]
Abstract
Although a number of international diet and lifestyle guidelines during pregnancy (DLGP) exist in the literature, contextualization to low- and middle-income settings is less common. The aim of this study was to present the Lebanese DLGP and to describe the process followed for their development. A mixed-method approach was used including a review and synthesis of existing international DLGP and a consensus building nominal group technique (NGT) with a multidisciplinary group of experts (n = 11). During the meeting, participants identified the themes of the guidelines, formulated the wording of each themes' guideline and translated the guidelines to the Arabic language. Consensus was defined as an agreement of 80%. Reviewing the literature, a list of 17 main topics were found to be common themes for the DLGP. For the Lebanese DLGP, participants in the NGT meeting selected seven themes from this list: gestational weight gain, diet diversity, hydration, food safety, harmful foods, physical activity and breastfeeding. In addition, the group formulated three themes based on merging/modifying existing themes: supplementation, alcohol and smoking and religious fasting. Two context-specific new themes emerged: wellbeing and nutrition resilience. For each of the identified themes, the group agreed upon the wording of its guidelines and description. This study is the first from the Eastern Mediterranean Region to develop through consensus building, context and culture-specific dietary and lifestyle guidelines for pregnant women. Putting maternal nutrition at the heart of tackling malnutrition and its detrimental health outcomes is a core investment for a better maternal and child health.
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Affiliation(s)
- Farah Naja
- Department of Clinical Nutrition and Dietetics, Research Institute of Medical & Health Sciences (RIMHS), College of Health SciencesUniversity of SharjahSharjahUnited Arab Emirates
- Department of Nutrition and Food SciencesAmerican University of BeirutBeirutLebanon
| | - Jennifer Ayoub
- Department of Nutrition and Food SciencesAmerican University of BeirutBeirutLebanon
| | - Samar Baydoun
- Faculty of Agricultural and Food Sciences/Faculty of Health SciencesAmerican University of BeirutBeirutLebanon
| | - Sahar Nassour
- Faculty of Agricultural and Food Sciences/Faculty of Health SciencesAmerican University of BeirutBeirutLebanon
| | - Pamela Zgheib
- Mother, Child and School Health UnitMinistry of Public HealthBeirutLebanon
| | - Lara Nasreddine
- Department of Nutrition and Food SciencesAmerican University of BeirutBeirutLebanon
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30
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Peng XF, Huang SF, Chen LJ, Xu L, Ye WC. Targeting epigenetics and lncRNAs in liver disease: From mechanisms to therapeutics. Pharmacol Res 2021; 172:105846. [PMID: 34438063 DOI: 10.1016/j.phrs.2021.105846] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/16/2021] [Accepted: 08/18/2021] [Indexed: 12/19/2022]
Abstract
Early onset and progression of liver diseases can be driven by aberrant transcriptional regulation. Different transcriptional regulation processes, such as RNA/DNA methylation, histone modification, and ncRNA-mediated targeting, can regulate biological processes in healthy cells, as well also under various pathological conditions, especially liver disease. Numerous studies over the past decades have demonstrated that liver disease has a strong epigenetic component. Therefore, the epigenetic basis of liver disease has challenged our knowledge of epigenetics, and epigenetics field has undergone an important transformation: from a biological phenomenon to an emerging focus of disease research. Furthermore, inhibitors of different epigenetic regulators, such as m6A-related factors, are being explored as potential candidates for preventing and treating liver diseases. In the present review, we summarize and discuss the current knowledge of five distinct but interconnected and interdependent epigenetic processes in the context of hepatic diseases: RNA methylation, DNA methylation, histone methylation, miRNAs, and lncRNAs. Finally, we discuss the potential therapeutic implications and future challenges and ongoing research in the field. Our review also provides a perspective for identifying therapeutic targets and new hepatic biomarkers of liver disease, bringing precision research and disease therapy to the modern era of epigenetics.
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Affiliation(s)
- Xiao-Fei Peng
- Department of General Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Shi-Feng Huang
- Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Ling-Juan Chen
- Department of Clinical Laboratory, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Lingqing Xu
- Department of Clinical Laboratory, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Wen-Chu Ye
- Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China.
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31
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Zhou J, Ma L, Zhao L, Sheng J, Xu Y, Chen J, Yu L, Sun Q, Zhou H, Zhu S, Lu Z, Wei B. Association Between the Prognostic Nutritional Index and Cognitive Function Among Older Adults in the United States: A Population-Based Study. J Alzheimers Dis 2021; 83:819-831. [PMID: 34366335 DOI: 10.3233/jad-210141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Nutritional status has been recognized as an important factor influencing cognitive function-related diseases, but few comprehensive nutrition indicators are available to assess the risk of cognitive decline. OBJECTIVE This study aimed to investigate the relationship between the prognostic nutritional index (PNI) and cognitive function in an elderly population, and the differences in nutrient intake between different levels of nutritional risk. METHODS Based on cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, we included 2,564 older participants. The lower quartile of each of the four cognitive tests was considered to have cognitive function impairment (CFI). Binary and multivariate logistic regression models were used to estimate the relationship between the PNI and the odds ratio of CFI. RESULTS After adjustment for confounding variables, we found that the odds of CFI were significantly lower for participants with normal PNI levels than for those with low PNI levels. In a comparison of global cognitive impairment scores, participants with a normal PNI had lower ratios of poor cognitive performance than those with a low PNI. By comparing the nutrient intake at different PNI levels, we found a reduction in the intake of protein, dietary fiber, total saturated fatty acids, and multiple micronutrients in the low PNI group. CONCLUSION Our study shows that the PNI can be a good predictor of the odds of CFI in the elderly population and that it is a convenient indicator of reduced intake of nutrients which may be important to brain health.
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Affiliation(s)
- Jie Zhou
- Department of Radiology, Shaoxing 7th People's Hospital, Shaoxing, Zhejiang Province, China
| | - Luping Ma
- Department of Radiology, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province, China
| | - Lulei Zhao
- Department of Radiology, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang Province, China
| | - Jiamin Sheng
- Department of Radiology, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province, China
| | - Yuhua Xu
- Department of Radiology, Shaoxing 7th People's Hospital, Shaoxing, Zhejiang Province, China
| | - Jie Chen
- Department of Laboratory Medicine, Shaoxing 7th People's Hospital, Shaoxing, Zhejiang Province, China
| | - Liangjun Yu
- Department of Radiology, Shaoxing 7th People's Hospital, Shaoxing, Zhejiang Province, China
| | - Quan Sun
- Department of Radiology, Shaoxing 7th People's Hospital, Shaoxing, Zhejiang Province, China
| | - Hangyang Zhou
- Department of Radiology, Zhuji Affiliated Hospital of Wenzhou Medical University, Shaoxing, Zhejiang Province, China
| | - Shaofeng Zhu
- Department of Radiology, Shaoxing 7th People's Hospital, Shaoxing, Zhejiang Province, China
| | - Zefeng Lu
- Department of Radiology, Shaoxing Second Hospital, Shaoxing, Zhejiang Province, China
| | - Bo Wei
- Department of Neurology, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China
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Scapaticci S, D’Adamo E, Mohn A, Chiarelli F, Giannini C. Non-Alcoholic Fatty Liver Disease in Obese Youth With Insulin Resistance and Type 2 Diabetes. Front Endocrinol (Lausanne) 2021; 12:639548. [PMID: 33889132 PMCID: PMC8056131 DOI: 10.3389/fendo.2021.639548] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 01/28/2021] [Indexed: 02/06/2023] Open
Abstract
Currently, Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent form of chronic liver disease in children and adolescents worldwide. Simultaneously to the epidemic spreading of childhood obesity, the rate of affected young has dramatically increased in the last decades with an estimated prevalence of NAFLD of 3%-10% in pediatric subjects in the world. The continuous improvement in NAFLD knowledge has significantly defined several risk factors associated to the natural history of this complex liver alteration. Among them, Insulin Resistance (IR) is certainly one of the main features. As well, not surprisingly, abnormal glucose tolerance (prediabetes and diabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. In addition, other factors such as genetic, ethnicity, gender, age, puberty and lifestyle might affect the development and progression of hepatic alterations. However, available data are still lacking to confirm whether IR is a risk factor or a consequence of hepatic steatosis. There is also evidence that NAFLD is the hepatic manifestation of Metabolic Syndrome (MetS). In fact, NAFLD often coexist with central obesity, impaired glucose tolerance, dyslipidemia, and hypertension, which represent the main features of MetS. In this Review, main aspects of the natural history and risk factors of the disease are summarized in children and adolescents. In addition, the most relevant scientific evidence about the association between NAFLD and metabolic dysregulation, focusing on clinical, pathogenetic, and histological implication will be provided with some focuses on the main treatment options.
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Affiliation(s)
| | | | | | | | - Cosimo Giannini
- Department of Pediatrics, University of Chieti, Chieti, Italy
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Inhibition of Dot1L Alleviates Fulminant Hepatitis Through Myeloid-Derived Suppressor Cells. Cell Mol Gastroenterol Hepatol 2021; 12:81-98. [PMID: 33497867 PMCID: PMC8081916 DOI: 10.1016/j.jcmgh.2021.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 01/14/2021] [Accepted: 01/14/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND & AIMS Fulminant hepatitis (FH) is a clinical syndrome characterized by sudden and severe liver dysfunction. Dot1L, a histone methyltransferase, is implicated in various physiologic and pathologic processes, including transcription regulation and leukemia. However, the role of Dot1L in regulating inflammatory responses during FH remains elusive. METHODS Propionibacterium acnes (P. acnes)-primed, lipopolysaccharides (LPS)-induced FH was established in C57BL/6 mice and was treated with the Dot1L inhibitor EPZ-5676. Myeloid derived suppressor cells (MDSCs) were depleted by anti-Gr-1 antibody to evaluate their therapeutic roles in Dot1L treatment of FH. Moreover, peripheral blood of patients suffered with FH and healthy controls was collected to determine the expression profile of Dot1L-SOCS1-iNOS axis in their MDSCs. RESULTS Here we identified that EPZ-5676, pharmacological inhibitor of Dot1L, attenuated the liver injury of mice subjected to FH. Dot1L inhibition led to decreased T helper 1 cell response and expansion of regulatory T cells (Tregs) during FH. Interestingly, Dot1L inhibition didn't directly target T cells, but dramatically enhanced the immunosuppressive function of MDSCs. Mechanistically, Dot1L inhibition epigenetically suppressed SOCS1 expression, thus inducing inducible nitric oxide synthase (iNOS) expression in a STAT1-dependent manner. Moreover, in human samples, the levels of Dot1L and SOCS1 expression were upregulated in MDSCs, accompanied by decreased expression of iNOS in patients with FH, compared with healthy controls. CONCLUSIONS Altogether, our findings established Dot1L as a critical regulator of MDSC immunosuppressive function for the first time, and highlighted the therapeutic potential of Dot1L inhibitor for FH treatment.
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Al-Okbi SY, Mohamed RS, Al-Siedy ESK, Mohammed SE. Functional Foods for Management of Diarrhea and Malnutrition in Rats Emphasizing on Nucleotides Role. Recent Pat Food Nutr Agric 2020; 11:257-270. [PMID: 32275496 DOI: 10.2174/2212798411666200410084202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 01/24/2020] [Accepted: 03/16/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Diarrhea and malnutrition are major health problems in developing countries. Inflammation, high oxidative stress, poor nutritional status, and fatty liver were encountered during such diseases. Patents for diarrhea and malnutrition management (WO2007/130882A2, WO00/37106A1, WO2014/152420, and CA2987364A1) were published. OBJECTIVE The objective was to introduce anti-diarrhea functional foods with a preventive effect on malnutrition. METHODS Two processing techniques were applied for preparing functional foods (formula 1 ingredients were made into cookies followed by grinding; formula 2 ingredients were pre-cooked, dried, and mixed in powder form) that were evaluated in a rat model of diarrhea with malnutrition (DM). Formula 2 was also assessed when mixed with nucleotides. The ingredients were edible plants that possess an anti-diarrheal effect with high protein sources (legumes and casein). RESULTS Induction of diarrhea with malnutrition, high oxidative stress, inflammation, accumulation of liver fat, and histopathological changes were demonstrated in DM control compared to normal control. The functional foods produced variable improvement in growth curves, food efficiency ratio, hemoglobin, hematocrit and plasma zinc, protein, albumin, globulin, lipase activity, and MDA. Formula 1 was superior in improving intestinal histopathology while formula 2 was more efficient in elevating plasma iron. Formula 2 with nucleotides was the best in improving growth curves, alkaline phosphatase, and reducing liver fat. Intestinal mucosa reduced glutathione and nitrite showed an efficient significant reduction on treatment with formula 2 with or without nucleotides. The formulas showed an anti-diarrheal effect by improving feces weight and moisture content. CONCLUSION Studied functional foods showed an anti-diarrheal effect and malnutrition improvement with different degrees.
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Affiliation(s)
| | - Rasha Salah Mohamed
- Department of Nutrition and Food Sciences, National Research Centre, Cairo, Egypt
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Mandala A, Janssen RC, Palle S, Short KR, Friedman JE. Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms. Nutrients 2020; 12:E3166. [PMID: 33081177 PMCID: PMC7602751 DOI: 10.3390/nu12103166] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 10/12/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the number one chronic liver disease worldwide and is estimated to affect nearly 40% of obese youth and up to 10% of the general pediatric population without any obvious signs or symptoms. Although the early stages of NAFLD are reversible with diet and lifestyle modifications, detecting such stages is hindered by a lack of non-invasive methods of risk assessment and diagnosis. This absence of non-invasive means of diagnosis is directly related to the scarcity of long-term prospective studies of pediatric NAFLD in children and adolescents. In the majority of pediatric NAFLD cases, the mechanisms driving the origin and rapid progression of NAFLD remain unknown. The progression from NAFLD to non-alcoholic steatohepatitis (NASH) in youth is associated with unique histological features and possible immune processes and metabolic pathways that may reflect different mechanisms compared with adults. Recent data suggest that circulating microRNAs (miRNAs) are important new biomarkers underlying pathways of liver injury. Several factors may contribute to pediatric NAFLD development, including high-sugar diets, in utero exposures via epigenetic alterations, changes in the neonatal microbiome, and altered immune system development and mitochondrial function. This review focuses on the unique aspects of pediatric NAFLD and how nutritional exposures impact the immune system, mitochondria, and liver/gastrointestinal metabolic health. These factors highlight the need for answers to how NAFLD develops in children and for early stage-specific interventions.
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Affiliation(s)
- Ashok Mandala
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
| | - Rachel C. Janssen
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
| | - Sirish Palle
- Department of Pediatrics, Section of Gastroenterology, Hepatology & Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA;
| | - Kevin R. Short
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
- Department of Pediatrics, Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Jacob E. Friedman
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
- Department of Pediatrics, Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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Dai X, Hou H, Zhang W, Liu T, Li Y, Wang S, Wang B, Cao H. Microbial Metabolites: Critical Regulators in NAFLD. Front Microbiol 2020; 11:567654. [PMID: 33117316 PMCID: PMC7575719 DOI: 10.3389/fmicb.2020.567654] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 09/04/2020] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease throughout the world. The relationship between gut microbiota and NAFLD has been extensively investigated. The gut microbiota is involved in the regulation of NAFLD by participating in the fermentation of indigestible food, interacting with the intestinal mucosal immune system, and influencing the intestinal barrier function, leading to signaling alteration. Meanwhile, the microbial metabolites not only affect the signal transduction pathway in the gut but also reach the liver far away from gut. In this review, we focus on the effects of certain key microbial metabolites such as short-chain fatty acids, trimethylamine-N-oxide, bile acids, and endogenous ethanol and indole in NAFLD, and also summarize several potential therapies targeting the gut-liver axis and modulation of gut microbiota metabolites including antibiotics, prebiotics, probiotics, bile acid regulation, and fecal microbiota transplantation. Understanding the complex interactions between microbial metabolites and NAFLD may provide crucial insight into the pathogenesis and treatment of NAFLD.
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Affiliation(s)
- Xin Dai
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Huiqin Hou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Wanru Zhang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Tianyu Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yun Li
- Department of Pharmacy, General Hospital, Tianjin Medical University, Tianjin, China
| | - Sinan Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
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Sandri BJ, Lubach GR, Lock EF, Georgieff MK, Kling PJ, Coe CL, Rao RB. Early-Life Iron Deficiency and Its Natural Resolution Are Associated with Altered Serum Metabolomic Profiles in Infant Rhesus Monkeys. J Nutr 2020; 150:685-693. [PMID: 31722400 PMCID: PMC7138653 DOI: 10.1093/jn/nxz274] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 07/23/2019] [Accepted: 10/11/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Iron deficiency is the most common nutrient deficiency in human infants aged 6 to 24 mo, and negatively affects many cellular metabolic processes, including energy production, electron transport, and oxidative degradation of toxins. There can be persistent influences on long-term metabolic health beyond its acute effects. OBJECTIVES The objective was to determine how iron deficiency in infancy alters the serum metabolomic profile and to test whether these effects persist after the resolution of iron deficiency in a nonhuman primate model of spontaneous iron deficiency. METHODS Blood was collected from naturally iron-sufficient (IS; n = 10) and iron-deficient (ID; n = 10) male and female infant rhesus monkeys (Macaca mulatta) at 6 mo of age. Iron deficiency resolved without intervention upon feeding of solid foods, and iron status was re-evaluated at 12 mo of age from the IS and formerly ID monkeys using hematological and other indices; sera were metabolically profiled using HPLC/MS and GC/MS with isobaric standards for identification and quantification at both time points. RESULTS A total of 413 metabolites were measured, with differences in 40 metabolites identified between IS and ID monkeys at 6 mo (P$\le $ 0.05). At 12 mo, iron-related hematological parameters had returned to normal, but the formerly ID infants remained metabolically distinct from the age-matched IS infants, with 48 metabolites differentially expressed between the groups. Metabolomic profiling indicated altered liver metabolites, differential fatty acid production, increased serum uridine release, and atypical bile acid production in the ID monkeys. CONCLUSIONS Pathway analyses of serum metabolites provided evidence of a hypometabolic state, altered liver function, differential essential fatty acid production, irregular uracil metabolism, and atypical bile acid production in ID infants. Many metabolites remained altered after the resolution of ID, suggesting long-term effects on metabolic health.
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Affiliation(s)
- Brian J Sandri
- Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
| | - Gabriele R Lubach
- Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI, USA
| | - Eric F Lock
- School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Michael K Georgieff
- Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA,Center for Neurobehavioral Development, University of Minnesota, Minneapolis, MN, USA
| | - Pamela J Kling
- Division of Neonatology, Department of Pediatrics, University of Wisconsin, Madison, WI, USA
| | - Christopher L Coe
- Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI, USA
| | - Raghavendra B Rao
- Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA,Center for Neurobehavioral Development, University of Minnesota, Minneapolis, MN, USA,Address correspondence to RBR (e-mail: )
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Bellanti JA. Epigenetic studies and pediatric research. Pediatr Res 2020; 87:378-384. [PMID: 31731288 DOI: 10.1038/s41390-019-0644-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 10/04/2019] [Accepted: 10/21/2019] [Indexed: 02/08/2023]
Abstract
The 2020 Annual Review Issue, "Preventing Disease in the 21st Century" was selected by the Editors-in-Chief of Pediatric Research to include a variety of disease entities that confront health-care practitioners entrusted to the care of infants and children. In keeping with this mandate, this article reviews the subject of epigenetics, which impacts pediatric research from bench to bedside. Epigenetic mechanisms exert their effects through the interaction of environment, various susceptibility genes, and immunologic development and include: (1) DNA methylation; (2) posttranslational modifications of histone proteins through acetylation and methylation, and (3) RNA-mediated gene silencing by microRNA (miRNA) regulation. The effects of epigenetics during fetal life and early periods of development are first reviewed together with clinical applications of cardiovascular and metabolic disorders in later life. The relationships of epigenetics to the allergic and autoimmune diseases and cancer are next reviewed. A specific focus of the article is directed to the recent recognition that many of these disorders are driven by aberrant immune responses in which immunoregulatory events are often poorly functioning and where through interventive epigenetic measures prevention may be possible by alterations in programming of DNA during fetal and early periods as well as in later life.
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Affiliation(s)
- Joseph A Bellanti
- Departments of Pediatrics and Microbiology-Immunology, Georgetown University Medical Center, Washington, DC, USA. .,International Center for Interdisciplinary Studies of Immunology (ICISI), Georgetown University Medical Center, Washington, DC, USA.
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Jonscher KR, Abrams J, Friedman JE. Maternal Diet Alters Trained Immunity in the Pathogenesis of Pediatric NAFLD. JOURNAL OF CELLULAR IMMUNOLOGY 2020; 2:315-325. [PMID: 33426540 PMCID: PMC7793570 DOI: 10.33696/immunology.2.061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Pediatric nonalcoholic fatty liver disease (NAFLD) affects 1 in 10 children in the US, increases risk of cirrhosis and transplantation in early adulthood, and shortens lifespan, even after transplantation. Exposure to maternal obesity and/or a diet high in fat, sugar and cholesterol is strongly associated with development of NAFLD in offspring. However, mechanisms by which "priming" of the immune system in early life increases susceptibility to NAFLD are poorly understood. Recent studies have focused on the role "non-reparative" macrophages play in accelerating inflammatory signals promoting fibrogenesis. In this Commentary, we review evidence that the pioneering gut bacteria colonizing the infant intestinal tract remodel the naïve immune system in the offspring. Epigenetic changes in hematopoietic stem and progenitor cells, induced by exposure to an obesogenic diet in utero, may skew lineage commitment of myeloid cells during gestation. Further, microbial dysbiosis in neonatal life contributes to training innate immune cell responsiveness in the gut, bone marrow, and liver, leading to developmental programming of pediatric NAFLD. Comprehensive understanding of how different gut bacteria and their byproducts shape development of the early innate immune system and microbiome will uncover early interventions to prevent NAFLD pathophysiology.
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Affiliation(s)
- Karen R. Jonscher
- Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, USA
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, USA
| | - Jesse Abrams
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, USA
| | - Jacob E. Friedman
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, USA
- Departments of Physiology and Pediatrics, University of Oklahoma Health Sciences Center, USA
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