Chaihu Guizhi Ganjiang Decoction Improves Non-alcoholic Fatty Liver in Rats Through RIP1/RIP3/MLKL Pathways Inhibiting Necrotic Apoptosis / 广州中医药大学学报

Objective To investigate the therapeutic effect and mechanism of Chaihu Guizhi Ganjiang Decoction on non-alcoholic fatty liver disease(NAFLD)rats.Methods The experiment was conducted in five groups:normal group,model group,low-and high-dose groups of Chinese medicine(Chaihu Guizhi Ganjiang Decoction)and GSK872[receptor interacting protein kinase(RIP)3 inhibitor]group.Except for the normal group,the NAFLD rat model was constructed using high-fat chow feeding method in the remaining groups,respectively.At the end of treatment,hepatocyte apoptosis was observed by terminal transferase uridyl nick end labeling(TUNEL)method,and serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),lipids[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],and the levels of inflammatory factors tumor necrosis factor α(TNF-α)and interleukin 1β(IL-1β)in liver tissues were measured by enzyme-linked immunosorbent assay(ELISA);and the levels of phosphorylation of RIP1,RIP3,and mixed lineage kinase structural domain-like protein(MLKL)were detected in liver tissues by Western Blot.Results Compared with the normal group,the apoptotic index of rat hepatocytes in the model group was elevated,ALT and AST in serum were significantly elevated,TC,TG and LDL-C levels were significantly elevated,and HDL-C level was significantly reduced,and the contents of TNF-α and IL-1β as well as the phosphorylated expression levels of RIP1,RIP3 and MLKL were significantly elevated in the liver tissues(P＜0.05);compared with the model group,the apoptotic index of hepatocytes in rats in the low-and high-dose groups of Chinese medicine and GSK872 group was reduced,the serum levels of ALT and AST were significantly reduced,the levels of TC,TG and LDL-C were significantly reduced,the level of HDL-C was significantly increased,and the contents of TNF-α and IL-1β and the phosphorylated expressions of RIP1,RIP3 and MLKL in the liver tissues were significantly reduced(P＜0.05);there was no significant difference in the above-mentioned indexes between the low-dose and high-dose groups of Chinese medicine and the GSK872 group(P＞0.05).Conclusion Chaihu Guizhi Ganjiang Decoction can effectively improve NAFLD in rats,and its mechanism may be related to the inhibition of RIP1/RIP3/MLKL signaling pathway activation,which in turn inhibits necrotic apoptosis.

Advances in epigenetics of nonalcoholic fatty liver desease / 复旦学报（医学版）

Nonalcoholic fatty liver disease(NAFLD)is a metabolic liver disease that ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis(NASH).NASH is characterized by persistent liver damage,inflammation,and fibrosis which significantly increases the risk of end-stage liver diseases,such as liver cirrhosis and hepatocellular carcinoma.The pathogenesis of NAFLD/NASH is not yet fully understood,but its recent epigenetic advances have provided new insights into the mechanisms of this disease.This review summarized recent progress in this area which has laid a solid foundation for elucidating the pathogenesis of NAFLD and provides potential targets for early detection,diagnosis,and treatment of this disease.

The Role of Nrf2 in Exercise Improving of NAFLD / 生物化学与生物物理进展

In cardiovascular disorders, neurological diseases, and chronic metabolic diseases, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is essential for maintaining cell homeostasis. According to studies, boosting Nrf2 expression can be used to cure or prevent chronic diseases that are characterized by oxidative stress, inflammation, and mitochondrial dysfunction. Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease characterized by hepatic steatosis brought on by a number of causes other than alcohol. In recent years, its incidence has gradually risen across the globe. According to relevant studies, NAFLD and the Nrf2 signaling pathway are tightly connected. Inhibiting lipid production and metabolism-related enzymes, repairing impaired liver metabolism, and lowering hepatic lipid storage are all possible with Nrf2 activation. Exercise is a powerful tool for treating and preventing NAFLD. However, exercise type, exercise intensity, environment, and exhaustion all have an impact on the Nrf2 signaling pathway. By activating Nrf2, exercise can lessen liver inflammation, oxidative stress, endoplasmic reticulum stress, and insulin resistance, and ameliorate liver damage to improve NAFLD. The activation of Nrf2 signaling pathway, its associated mechanism of controlling antioxidation, and the impact of exercise on the Nrf2 signaling pathway are all explained in this work. Based on the pathogenesis of NAFLD, this article examines the connection between exercise, Nrf2, and NAFLD, and the current state of knowledge regarding Nrf2’s role in the amelioration of NAFLD through exercise. It offers a theoretical frame of reference for future research into how Nrf2 might be used to improve NAFLD.

Insulin-like growth factor binding protein 3 promoter variant (rs2854744) is associated with nonalcoholic fatty liver disease

ABSTRACT Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (−202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The "GT+TT" genotype of the IGFBP3 rs2854744 polymorphism, compared with the "GG" genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 "T" allele, in comparison with the "G" allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 "GT+TT" genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

Independent predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B

SUMMARY OBJECTIVE: There are limited data on non-alcoholic fatty liver disease in chronic hepatitis B virus infection. We aimed to determine the predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B virus infection. METHODS: All consecutive treatment-naïve patients with chronic hepatitis B virus infection at the Haseki Training and Research Hospital between October 1, 2021, and September 31, 2022, were retrospectively enrolled. Chronic hepatitis B virus infection is defined by positive serum hepatitis B surface antigen for 6 months or more. Patients with significant alcohol consumption, prolonged steatogenic drug use, malignancy, monogenic hereditary disorders, patients co-infected with hepatitis D virus, hepatitis C virus infection, or human immunodeficiency virus were excluded. Demographic characteristics, anthropometric determinants, laboratory findings, and virological parameters were retrospectively collected from patients' charts and electronic medical records. RESULTS: A total of 457 patients with treatment-naïve chronic hepatitis B virus infection were included in the study. The three multivariate regression models revealed that age (p<0.028), body mass index (p=0.046), diabetes mellitus (p=0.030), hemoglobin (p=0.008), platelet (p=0.012), and triglyceride (p=0.002) in Model 1; body mass index (p=0.033), diabetes mellitus (p<0.001), hemoglobin (p=0.008), platelet (p=0.004), LDL (p=0.023), and HDL (p=0.020) in Model 2; and age (p<0.001), body mass index (p=0.033), hemoglobin (p=0.004), platelet (p=0.004), and HDL (p=0.007) in Model 3 were independent predictors. CONCLUSION: Non-alcoholic fatty liver disease was observed in about one-third of patients with chronic hepatitis B virus infection and was positively associated with older age, higher body mass index, presence of comorbid conditions including diabetes mellitus, increased levels of metabolic laboratory parameters, especially serum triglyceride and LDL, and decreased HDL.

The rs1862513 promoter variant of resistin gene influences susceptibility to nonalcoholic fatty liver disease

SUMMARY OBJECTIVES: Nonalcoholic fatty liver disease is the term used for a range of conditions in which fat builds up in the liver and exceeds 5% of hepatocytes without inordinate alcohol intake or other causes of lipid accumulation. Regarding the fact that insulin resistance and obesity play key roles in the pathogenesis of nonalcoholic fatty liver disease, as well as the connection between resistin and these metabolic diseases, the association between nonalcoholic fatty liver disease and a resistin gene (RETN) polymorphism was examined. METHODS: In this genetic case-control association study, 150 biopsy-proven nonalcoholic fatty liver disease patients and 154 controls were enrolled and genotyped for the RETN rs1862513 (-420C>G) gene polymorphism using PCR-RFLP method. RESULTS: The −420C>G genotype frequency distributions in both groups were consistent with Hardy-Weinberg equilibrium (HWE; p>0.05). The carriers of the RETN −420C>G "CC" genotype compared with the "GG" genotype occurred less frequently in the cases with nonalcoholic fatty liver disease than in the controls, and the difference remained significant even after adjustment for confounding factors (p=0.030; OR=0.47, 95%CI=0.36-0.93). Interestingly, the RETN −420C>G "C" allele was also associated with a decreased risk for nonalcoholic fatty liver disease too (p=0.042; OR=0.72, 95%CI=0.53-0.95). CONCLUSION: We found for the first time an association between biopsy-proven nonalcoholic fatty liver disease and RETN −420C>G promoter polymorphism. The carriers of the RETN −420C>G "CC" genotype had a 53% decreased risk for nonalcoholic fatty liver disease. Our findings, however, need to be corroborated by further studies.

NAMPT gene rs2058539 variant is a risk factor for nonalcoholic fatty liver disease

SUMMARY OBJECTIVE: Nonalcoholic fatty liver disease is a chronic liver disease and a growing global epidemic. The aim of this study was to investigate the association between a visfatin gene (NAMPT) variant and nonalcoholic fatty liver disease, owing to the connection between this disease and insulin resistance, obesity, inflammation, and oxidative stress, and the role of visfatin in these metabolic disorders. METHODS: In the present case-control study, we enrolled 312 genetically unrelated individuals, including 154 patients with biopsy-proven nonalcoholic fatty liver disease and 158 controls. The rs2058539 polymorphism of NAMPT gene was genotyped using the PCR-RFLP method. RESULTS: Genotype and allele distributions of NAMPT gene rs2058539 polymorphism conformed to the Hardy-Weinberg equilibrium both in the case and control groups (p>0.05). The distribution of NAMPT rs2058539 genotypes and alleles differed significantly between the cases with nonalcoholic fatty liver disease and controls. The "CC" genotype of the NAMPT rs2058539 compared with "AA" genotype was associated with a 2.5-fold increased risk of nonalcoholic fatty liver disease after adjustment for confounding factors [p=0.034; odds ratio (OR)=2.52, 95% confidence interval (CI)=1.36-4.37]. Moreover, the NAMPT rs2058539 "C" allele was significantly overrepresented in the nonalcoholic fatty liver disease patients than controls (p=0.022; OR=1.77, 95%CI=1.14-2.31). CONCLUSION: Our findings indicated for the first time that the NAMPT rs2058539 "CC" genotype is a marker of increased nonalcoholic fatty liver disease susceptibility; however, it needs to be supported by further investigations in other populations.

Efficacy of nutrition therapy with food rich in methionine for treating nonalcoholic fatty liver / Eficacia de la terapia nutricional con alimentos ricos en metionina para el tratamiento de hígado graso no alcohólico

Non-Alcoholic Fatty Liver disease (NAFLD) can lead to Non Alcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The treatment for NAFLD involves modification of caloric intake and physical activity. NAFLD has a pro-oxidant nature; therefore, it is logical to suppose that the antioxidant methionine can be used as a treatment for this disease. Aim. This study aimed to evaluate the effect of high-methionine dietary therapy on patients with NAFLD. Materials and methods. A randomized clinical study was conducted over three months. In this study, 121 NAFLD patients participated, and the age of the participants was ≥ 20 years (experimental group included 56 and control group 65), all of whom were randomized and matched by sex, recluted from the ISSSTE hospital in Xalapa, Mexico. The patients were instructed to consume food to cover the recommended methionine daily doses, and the daily amount consumed was calculated. Methionine effect was measured as NAFLD regression and quality of life improvement. Results. Nutritional therapy induced NAFLD regression and diminished central fat accumulation, blood pressure, and the fatty liver index. Some parameters, such as liver enzymes, did not changed. The quality of life of patients improved after treatment. Conclusions. In this study, we show a hepatoprotective effect induced only in three months of chances in the diet, thus, a longer diet may generate more relevant benefits in the resistant parameters of our study(AU)

La enfermedad del hígado graso no alcohólico (NAFLD) puede conducir a la esteatohepatitis no alcohólica (NASH), la cirrosis y el cáncer de hígado. El tratamiento para NAFLD es la modificación de la ingesta calórica y la actividad física. Debido a que NAFLD tiene una naturaleza pro-oxidante; es lógico suponer que el antioxidante metionina puede utilizarse en el tratamiento de esta enfermedad. Objetivo. el presente trabajo evaluó el papel de la terapia nutricional con alimentos ricos en metioninaen pacientes con NAFLD. Materiales y Métodos. Se realizó un ensayo clínico aleatorizado durante tres meses. Participaron en el estudio 121 pacientes con NAFLD con edad ≥ 20 años (56 en el grupo experimental y 65 en el control), todos aleatorizados y pareados por sexo, reclutados de la Clínica Hospital ISSTE en la ciudad de Xalapa, México, en el año 2015. Se instruyó a los pacientes en consumir los alimentos hasta completar la dosis diaria recomendada de metioninay se calculó la cantidad diaria consumida. Su efecto se midió como la regresión de NAFLD y la mejora de la calidad de vida. Resultados. La terapia nutricional retrocedió NAFLD; disminuyó la acumulación de grasa central, la presión arterial y el índice de hígado graso. Algunos parámetros, como las enzimas de la función hepática, no se modificaron con el tratamiento. Otro parámetro fue la mejora de la calidad de vida de los pacientes tratados. Conclusiones. En este trabajo mostramos un impacto hepatoprotector producido con tan solo tres meses de cambios en la dieta, por lo que una dieta más prolongada podría generar beneficios aún más significativos en los parámetros resistentes en nuestro protocolo(AU)

A study on parathyroid hormone and Vitamin D levels in patients with non-alcoholic fatty liver disease

Background: One of the most prevalent chronic liver ailments is non-alcoholic fatty liver disease (NAFLD). The correction of numerous genes connected to various metabolic diseases depends heavily on Vitamin D. Aims and Objectives: This investigation was intended to look at the relationships among those with NAFLD serum levels of Vitamin D, parathyroid hormone (PTH), insulin, and insulin resistance (IR). Materials and Methods: Two hundred and fifty patients with NAFLD and 250 age-matched participants without NAFLD served as the study’s control group. Serum Vitamin D, PTH, insulin, and fasting blood glucose (FBG) levels were measured after 8–12 h of not eating or drinking. By controlling for the independent factors, the multivariate logistic regression analysis model was utilized to assess the relationship between Vitamin D, PTH, and IR in the occurrence of NAFLD. Results: When compared to controls, patients with NAFLD had significantly lower serum Vitamin D levels and higher levels of PTH, insulin, and FBG (P = 0.001). Confounders had no impact on the association between NAFLD and the lower Vitamin D readings. Conclusions: Our findings demonstrated that raised insulin and IR values and lower serum Vitamin D concentrations were each independently related with an increased risk of having NAFLD.

Effect of Dendrobii Caulis Mixture on Cell Inflammatory Response and Apoptosis in Diabetic Rats with Nonalcoholic Fatty Liver Disease Based on NF-κB/NLRP3/IL-1β Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Dendrobii Caulis mixture on cell inflammatory response and apoptosis in diabetic rat with non-alcoholic fatty liver disease（NAFLD） and its possible mechanism. MethodForty male SD rats were randomly divided into blank group and model group of type 2 diabetes mellitus（T2DM） with NAFLD according to body weight. The model was established by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ）， which was randomly divided into the model group， Dendrobii Caulis mixture group（16.67 g·kg-1·d-1） and metformin group（100 mg·kg-1·d-1） according to blood glucose and body weight， and 10 rats in each group. Rats in each group were administered by continuous gavage for 4 weeks， the blank and model groups were given saline by gavage at 10 mL·kg-1·d-1. Fasting blood glucose（FBG）， serum insulin（INS）， glycosylated serum protein（GSP）， triglyceride（TG）， total cholesterol（TC）， high density lipoprotein（HDL-C）， low density lipoprotein（LDL-C）， alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were detected in each group of rats. The liver tissues of rats in each group were stained with hematoxylin-eosin（HE） to observe the pathological changes， and the positive expressions of nuclear transcription factor（NF）-κB， NOD-like receptor heat protein structural domain-related protein 3（NLRP3）， interleukin（IL）-1β and tumor necrosis factor（TNF）-α were observed by immunohistochemistry. Western blot and fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression of B-cell lymphoma-2（Bcl-2）， Bcl-2 associated X protein（Bax）， Caspase-3 and NF-κB p65， NLRP3， IL-1β， TNF-α in liver tissue of rats in each group. ResultCompared with the blank group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels were increased， INS and HDL-C levels were decreased， Bax， Caspase-3， NLRP3， IL-1β， TNF-α protein and mRNA expression were increased in model group， the ratio of p-NF-κB/NF-κB protein increased， the expression of Bcl-2 protein and mRNA decreased， and the positive immunohistochemical expression of NF-κB， NLRP3， IL-1β and TNF-α increased， and the differences were statistically significant（P<0.01）. The morphological structure of the liver was disrupted， and obvious fat vacuoles were seen. Compared with the model group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels of Dendrobii Caulis mixture group and metformin group were decreased， INS and HDL-C levels were increased， and protein and mRNA expressions of Bax， Caspase-3， NLRP3， IL-1β and TNF-α were decreased， the protein ratio of p-NF-κB/NF-κB decreased， the expression of Bcl-2 protein and mRNA increased， and the positive immunohistochemical expressions of NF-κB， NLRP3， IL-1β and TNF-α decreased， and the differences were statistically significant（P<0.01）. The liver morphology and structure were relatively complete， and the fat vacuoles were reduced. ConclusionDendrobii Caulis mixture can inhibit cell apoptosis， reduce inflammatory response and alleviate liver injury in rats with T2DM and NAFLD， the mechanism may be related to inhibiting the activation of NF-κB pathway， blocking the activation of NLRP3 inflammatory vesicles， reducing IL-1β secretion， attenuating Caspase-3 activity and reducing the ratio of Bcl-2/Bax.

Prevention and Treatment of NAFLD with Traditional Chinese Medicine Monomers by Regulating AMPK Pathway： A Review / 中国实验方剂学杂志

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease with complex and diverse pathogenesis， and there is no effective treatment or specific drugs for its clinical treatment. In recent years， its incidence has been on the rise， and it has become the earnest expectation of medical researchers in China and abroad that related patients could be treated. AMP-activated protein kinase （AMPK） functions to regulate cellular energy homeostasis and mitochondrial homeostasis. When activated， it has a good intervention effect on NAFLD progression with lipid metabolism disorders and mitochondrial homeostasis disorders. For NAFLD， the activation of AMPK can inhibit the production of new lipogenesis in the liver， promote the oxidation of fatty acids in the liver， and enhance the mitochondrial function of adipose tissues. As a key target of metabolic diseases， AMPK can also improve apoptosis， liver fibrosis， autophagy， and inflammation. Traditional Chinese medicine （TCM） is good at treating diseases from multiple targets and multiple pathways and is also commonly used in the treatment of chronic liver disease in clinical practice. A large number of in vitro and in vivo experimental studies on NAFLD have shown that TCM monomers have good prospects for the treatment of NAFLD through the AMPK signaling pathway， including glycosides， phenols， alkaloids， flavonoids， quinones， terpenoids， and lignans， which are natural activators of AMPK. This study reviewed the research progress on TCM monomers in regulating the AMPK pathway to prevent and treat NAFLD， providing a broader perspective for TCM treatment of NAFLD.

Expression and functions of transient receptor potential channels in liver diseases

Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults, to inflammation, subsequent fibrosis and hepatoma. We also explore expression levels of TRPs in liver tissues of ALD, NAFLD and HCC patients from Gene Expression Omnibus (GEO) or The Cancer Genome Atlas (TCGA) database and survival analysis estimated by Kaplan-Meier Plotter. At last, we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver diseases. The aim is to provide a better understanding of the implications of TRP channels in liver diseases, contributing to the discovery of novel therapeutic targets and efficient drugs.

The deubiquitinating enzyme 13 retards non-alcoholic steatohepatitis via blocking inactive rhomboid protein 2-dependent pathway

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Mechanisms of cholesterol metabolism imbalance in a PA-induced non-alcoholic fatty liver disease cell model / 中国药科大学学报

@#Liver cholesterol metabolism disorder plays an important role in the development of non-alcoholic fatty liver disease (NAFLD).In order to reveal the molecular mechanism of cholesterol homeostasis imbalance induced by saturated fatty acids, HepG2 cells were stimulated with palmitic acid (PA).Lipids accumulation was analyzed by Oil Red O staining, intracellular triglyceride and cholesterol quantification.The level of genes and proteins related to cholesterol homeostasis was measured by RT-qPCR and western blotting.Additionally, intracellular bile acids and mitochondrial oxysterols were detected by LC-MS/MS.The results demonstrated that intracellular lipids such as TG and TC were significantly increased in the model with PA stimulation.Although no significant difference was detected in genes related to cholesterol synthesis and uptake, the protein expression of ABCG5 and LXRα were significantly down-regulated, indicating a decrease in cholesterol efflux.Meanwhile, the gene expression of STARD1 and CYP7B1, which are responsible for bile acid alternative synthesis, were markedly enhanced, along with a significant increase of cholesterol and 27-OHC in mitochondria and CDCA in cells.These results suggested that PA overload may disrupt cholesterol homeostasis by inhibiting cholesterol efflux and promoting bile acids synthesis.

Research progress of the impact of nonalcoholic fatty liver disease on chronic hepatitis B infection / 上海交通大学学报（医学版）

Chronic hepatitis B(CHB)is an infectious disease caused by persistent infection with the hepatitis B virus(HBV)and is highly prevalent worldwide.Non-alcoholic fatty liver disease(NAFLD)is a group of liver diseases related to metabolic abnormalities,excluding those caused by alcohol consumption or other liver injury factors.In recent years,with improvement of living standards and changes in lifestyle,the incidence of NAFLD has been increasing substantially,becoming the most common type of liver diseases in China and Western countries,and the second leading cause of liver transplantation in the West.The rising prevalence of NAFLD has also led to an increase in the incidence of NAFLD in patients with chronic HBV infection.However,there is considerable controversy both domestically and internationally regarding the relationship between these two diseases,including the disease progression,pathogenesis,impact on antiviral treatment efficacy,and prognosis of these concomitant CHB and NAFLD patients.Currently,both domestic and international guidelines lack detailed descriptions of diagnostic and treatment strategies for these conditions.This article summarizes the recent research progress in concomitant CHB and NAFLD,including epidemiology,diagnostic criteria,the impact of NAFLD on the virology of HBV infection,potential mechanisms of NAFLD-induced negative regulation of HBV,the effect of NAFLD on antiviral therapy effiicacy,and prognosis.This article aims to gain a deeper understanding of the diseases themselves and provide new insights for basic and clinical research as well as diagnostic and treatment approaches.

Protective Effect and Mechanism of Youning Bawei Powder on Dexamethasone Induced Non-alcoholic Fatty Liver Disease in Rats / 世界科学技术-中医药现代化

Objective To investigate the protective effect of Mongolian Medicine Youning Bawei Powder(MMYBP)on the liver of non-alcoholic fatty liver disease(NAFLD)model rats and its mechanism.Methods SD rats were randomly divided into normal group,model group,Yi Shan Fu group,MMYBP high and low dose groups.The normal group was fed with ordinary diet,and the other four groups were injected with dexamethasone and fed with high-fat diet,then establish NAFLD model.NAFLD model was treated with Yi Shan Fu,MMYBP high dose and low dose for one month.The liver index and pathological changes of liver tissue were detected.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG)and liver triglyceride(TG),malondialdehyde(MDA),superoxide dismutase(SOD)and free fatty acid(FFA)indexes were measured by enzyme linked immunosorbent assay(ELISA).The expression level of CYP2E1 mRNA in liver tissue was measured by reverse transcription PCR(RT-PCR).The expression of cytochrome P4502E1(CYP2E1)protein in liver tissue was measured by Western blot.Results The liver index of MMYBP high dose group was significantly lower than that of model group(P<0.05).The contents of AST,ALT and TG in serum were significantly lower than those in model group(P<0.05).The contents of TG,FFA and MDA in liver tissue were significantly lower than those in model group(P<0.05).The pathological changes of liver were significantly improved compared with the model group.The expression levels of CYP2E1 protein and CYP2E1 mRNA in liver tissue were significantly lower than those in model group.Conclusion MMYBP can reduce the expression level of CYP2E1 protein and CYP2E1 mRNA related to lipid metabolism in NAFLD,improve liver function and lipid metabolism disorder,reduce lipid and protect liver in NAFLD,and delay the progression of NAFLD to liver fibrosis and cirrhosis.

New discoveries in the field of metabolism by applying single-cell and spatial omics / 药物分析学报

Single-cell multi-Omics(SCM-Omics)and spatial multi-Omics(SM-Omics)technologies provide state-of-the-art methods for exploring the composition and function of cell types in tissues/organs.Since its emergence in 2009,single-cell RNA sequencing(scRNA-seq)has yielded many groundbreaking new discoveries.The combination of this method with the emergence and development of SM-Omics tech-niques has been a pioneering strategy in neuroscience,developmental biology,and cancer research,especially for assessing tumor heterogeneity and T-cell infiltration.In recent years,the application of these methods in the study of metabolic diseases has also increased.The emerging SCM-Omics and SM-Omics approaches allow the molecular and spatial analysis of cells to explore regulatory states and determine cell fate,and thus provide promising tools for unraveling heterogeneous metabolic processes and making them amenable to intervention.Here,we review the evolution of SCM-Omics and SM-Omics technologies,and describe the progress in the application of SCM-Omics and SM-Omics in metabolism-related diseases,including obesity,diabetes,nonalcoholic fatty liver disease(NAFLD)and cardiovascular disease(CVD).We also conclude that the application of SCM-Omics and SM-Omics approaches can help resolve the molecular mechanisms underlying the pathogenesis of metabolic diseases in the body and facilitate therapeutic measures for metabolism-related diseases.This review concludes with an overview of the current status of this emerging field and the outlook for its future.

Echinatin down-regulates ASKl-JNK signaling pathway against FFA induced non-alcoholic fatty liver disease / 中国药理学通报

Aim To investigate the effect of echinatin on the non-alcoholic fatty liver disease model of free fatty acids ( FFA) -induced HepG2 cells and its mechanism. Methods The experimental groups were divided into control group, FFA model group and echinatin group (0.3 , 1, 3 μmol • L

Research advances of lncRNAs in nonalcoholic fatty liver disease / 中国药理学通报

Long non-coding RNAs (lncRNAs), a class of noncoding RNAs, are commonly defined as RNA molecules more than 200 nucleotides in length. LncRNA has been shown to get involved in various biological processes, such as chromatin modification, transcriptional activation and intranuclear transport. Emerging research have also indicated that lncRNA plays a vital role in the pathological processes of many diseases. Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases with an increasing incidence. Recent studies have confirmed that lncRNAs are key contributors to pathological processes that are underpinning the initiation and progression of NAFLD, including insulin resistance, lipid metabolism disorders and inflammation. This review summarizes the findings of the role of lncRNAs in the pathological processes of NAFLD that have obtained to date, in order to provide a theoretical basis for the prevention, treatment, clinical detection of NAFLD, and the development of innovative anti-NAFLD drugs.

An Artificial Neural Network Model Combined with Dietary Retinol Intake from Different Sources to Predict the Risk of Nonalcoholic Fatty Liver Disease / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to develop an artificial neural network (ANN) model combined with dietary retinol intake from different sources to predict the risk of non-alcoholic fatty liver disease (NAFLD) in American adults.@*METHODS@#Data from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) 2007-2014 were analyzed. Eligible subjects ( n = 6,613) were randomly divided into a training set ( n 1 = 4,609) and a validation set ( n 2 = 2,004) at a ratio of 7:3. The training set was used to identify predictors of NAFLD risk using logistic regression analysis. An ANN was established to predict the NAFLD risk using a training set. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of the model using the training and validation sets.@*RESULTS@#Our study found that the odds ratios ( ORs) and 95% confidence intervals ( CIs) of NAFLD for the highest quartile of plant-derived dietary retinol intake (i.e., provitamin A carotenoids, such as β-carotene) ( OR = 0.75, 95% CI: 0.57 to 0.99) were inversely associated with NAFLD risk, compared to the lowest quartile of intake, after adjusting for potential confounders. The areas under the ROC curves were 0.874 and 0.883 for the training and validation sets, respectively. NAFLD occurs when its incidence probability is greater than 0.388.@*CONCLUSION@#The ANN model combined with plant-derived dietary retinol intake showed a significant effect on NAFLD. This could be applied to predict NAFLD risk in the American adult population when government departments formulate future health plans.