In order to increase activity of Cu Fe catalyst and use the mixture of nitrogen and hydrogen directly for preparation of high alcohols by reducing fatty acid esters, rare earths were used to modify the catalyst. Expe...In order to increase activity of Cu Fe catalyst and use the mixture of nitrogen and hydrogen directly for preparation of high alcohols by reducing fatty acid esters, rare earths were used to modify the catalyst. Experiments show that yield of high alcohols increases by 3% as 1% Sm 2O 3 is added to the catalyst when the reduction is carried out under pure hydrogen. The yield greatly decreases when the reduction is carried out under the mixture of hydrogen and nitrogen. Catalysts activities modified by Y and Nd can be evidently improved and even enhanced. The yields increase by 33% and 29% when 1% Y 2O 3 and 1% Nd 2O 3 are added to the catalyst, respectively.展开更多
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, succ...BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, successful treatment options are limited. One of the main barriers to finding safe and effective drugs for long-term use in NAFLD is the fast initiation and progression of disease in the available preclinical models. Therefore, we are in need of preclinical models that (1) mimic the human manifestation of NAFLD and (2) have a longer progression time to allow for the design of superior treatments. AIM To characterize a model of prolonged high-fat diet (HFD) feeding for investigation of the long-term progression of NAFLD. METHODS In this study, we utilized prolonged HFD feeding to examine NAFLD features in C57BL/6 male mice. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 80 wk to promote obesity (Old-HFD group, n = 18). A low-fat diet (LFD)(14% fat, 32% protein, and 54% carbohydrate) was administered for the same duration to age-matched mice (Old-LFD group, n = 15). An additional group of mice was maintained on the LFD (Young-LFD, n = 20) for a shorter duration (6 wk) to distinguish between age-dependent and age-independent effects. Liver, colon, adipose tissue, and feces were collected for histological and molecular assessments.RESULTS Prolonged HFD feeding led to obesity and insulin resistance. Histological analysis in the liver of HFD mice demonstrated steatosis, cell injury, portal and lobular inflammation and fibrosis. In addition, molecular analysis for markers of endoplasmic reticulum stress established that the liver tissue of HFD mice have increased phosphorylated Jnk and CHOP. Lastly, we evaluated the gut microbial composition of Old-LFD and Old-HFD. We observed that prolonged HFD feeding in mice increased the relative abundance of the Firmicutes phylum. At the genus level, we observed a significant increase in the abundance of Adercreutzia, Coprococcus, Dorea, and Ruminococcus and decreased relative abundance of Turicibacter and Anaeroplasma in HFD mice. CONCLUSION Overall, these data suggest that chronic HFD consumption in mice can mimic pathophysiological and some microbial events observed in NAFLD patients.展开更多
Introduction: Alcohol drinking and risky sexual practices have become serious public health problem among teenagers and young adults globally, including many developing countries. The available reports are sparse, esp...Introduction: Alcohol drinking and risky sexual practices have become serious public health problem among teenagers and young adults globally, including many developing countries. The available reports are sparse, especially there is a lack of recent and representative data for high school students in developing countries including Ethiopia. The aim of this study was to estimate the prevalence, identify determinants, and examine the association of alcohol drinking with sexual practices among high school students in Addis Ababa, capital city of Ethiopia. Methods: School based cross sectional study was conducted from November to December 2010. Multivariate logistic regression analysis was used to determine the association between students’ background characteristics and alcohol use, and alcohol use and sexual practices. Results: Among 2551 students surveyed, lifetime and current (past month) alcohol drinking was reported by 1166 (45.7%) and 676 (26.5%) students, respectively. Having sexual intercourse at least once in their lifetime was reported by 412 (16.2%) with151 (5.9%) of them being sexually active during a month prior to the survey. Having multiple sexual partners (52.5%), drinking alcohol before sexual intercourse (26.4%), and having sexual intercourse without the use of condom (47.3%) were also common among sexually active students. In adjusted logistic regression model, age (18 and 19 and older), living with 2 parents, getting pocket money, having alcohol drinking friends and attending general secondary school (grade 9-10) were positive predictors of current alcohol drinking. Nergative predictors of current alcohol drinking were being Protestant Christian and living with relatives or siblings. Conclusion: Alcohol drinking before sexual intercourse was a major problem among high school students in Addis Ababa, Ethiopia. Male gender, older age and higher school grade, friends influence, religious affiliation, living with parents and getting pocket money were significant predictors of current alcohol drinking. Educating about substance use and risky sexual behaviors, engaging students in extracurricular activities and restrict access to alcohol to high school students may help in solution of these problems on a local scale.展开更多
BACKGROUND Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for therapy of nonalcoholic fatty liver disease(NAFLD).Polygonatum kin...BACKGROUND Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for therapy of nonalcoholic fatty liver disease(NAFLD).Polygonatum kingianum(PK)has been traditionally used in China as a medicinal and nutritional ingredient for centuries and can alleviate high-fat diet(HFD)-induced NAFLD by promoting mitochondrial functions.To date,the underlying molecular mechanism of PK for treating mitochondrial dysfunctions and thus alleviating NAFLD remains unclear.AIM To identify the molecular mechanism behind the mitochondrial regulatory action of PK against HFD-induced NAFLD in rats.METHODS NAFLD model was induced in rats with HFD.The rats were intragastrically administered PK(4 g/kg per day)for 14 wk.Metabolites in hepatic mitochondrial samples were profiled through ultra-high performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to find the potential biomarkers and metabolic pathways.RESULTS PK significantly restored the metabolites’levels in the mitochondrial samples.Ten potential biomarkers were identified in the analyzed samples.These biomarkers are involved in riboflavin metabolism.CONCLUSION PK can alleviate HFD-induced NAFLD by regulating the riboflavin metabolism and further improving the mitochondrial functions.Thus,PK is a promising mitochondrial regulator/nutrient for alleviating NAFLD-associated diseases.展开更多
The contributions of tetrahydrofurfuryl alcohol (THFA) and polyethylene glycol (PEG) to the renatured efficiency of a-chymotrypsin were investigated and compared with each other. The maximum increments of bioactivity...The contributions of tetrahydrofurfuryl alcohol (THFA) and polyethylene glycol (PEG) to the renatured efficiency of a-chymotrypsin were investigated and compared with each other. The maximum increments of bioactivity recovery of a-Chy were found to be 25.1% for THFA, 10.4% for PEG, respectively. The experimental results indicated that the denaturant solution containing THFA contributed more to the renaturation of a-Chy in high performance hydrophobic interaction chromatography (HPHIC) than that containing PEG, when the concentration of THFA was 3.2%, the bioactivity recovery of a-Chy is the highest.展开更多
为了探究草菇子实体多肽(Volvariella volvacea fruit body polypeptides,VVFP)对模型小鼠急性酒精肝预防作用及肠道菌群的影响,以先前获得的VVFP(分子质量1~3 kDa)为材料灌胃小鼠,将小鼠随机分为空白组、模型组、阳性对照组、多肽低剂...为了探究草菇子实体多肽(Volvariella volvacea fruit body polypeptides,VVFP)对模型小鼠急性酒精肝预防作用及肠道菌群的影响,以先前获得的VVFP(分子质量1~3 kDa)为材料灌胃小鼠,将小鼠随机分为空白组、模型组、阳性对照组、多肽低剂量组、多肽中剂量组、多肽高剂量组,比较各组小鼠的血清和肝脏指标以及组织病理切片,利用16S rDNA基因高通量测序分析各样品中微生物菌群的生物多样性以及在门和属水平上的相对丰度。结果表明,与模型组相比,VVFP能够极显著降低血清中甘油三酯、总胆固醇、谷丙转氨酶、谷草转氨酶水平和肝脏中丙二醛的含量,并且降低肿瘤坏死因子-α、白细胞介素-6炎症因子水平,同时明显提高肝脏中乙醇脱氢酶、总超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。16S rDNA基因高通量测序结果表明,VVFP可以使小鼠肠道菌群中α多样性的Chao1指数和Observed_species指数明显降低,Shannon指数升高,并可通过调节拟杆菌门、厚壁菌门、链霉菌属、乳酸杆菌属和弧菌属的丰度从而减轻小鼠肝脏的损伤程度。综上,VVFP可以减轻酒精引起的肝损伤,本研究可为多肽在功能食品领域的应用提供理论参考。展开更多
AIM:To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis(NASH),which has been a challenge.METHODS:In this study,we used a high fat diet(HFD)feeding supplemented with fructo...AIM:To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis(NASH),which has been a challenge.METHODS:In this study,we used a high fat diet(HFD)feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States.We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively,and evaluated the extent of liver damage,steatosis,and inflammasome activation.Our methods included histopathological analysis to assess liver damage and steatosis,which involved H and E and oil-red-o staining;biochemical studies to look at ALT and triglyceride levels;RNA analysis using quantitative polymerase chain reaction;and cytokine analysis,which included the enzyme-linked immunosorbent assay method to look at interleukin(IL)-1βand tumor necrosis factor-α(TNFα)levels.Furthermore,at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests(ITT)and glucose tolerance tests.RESULTS:There was no insulin resistance,steatosis,or inflammasome activation at 6 wk.In contrast,at16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male,but not female mice.In males,elevated alanine aminotransferase and triglyceride levels,indicated liver damage and steatosis,respectively.Increased liver TNFαand monocyte chemoattractant protein-1 mRNA and protein,correlated with steatohepatitis.The inflammasome components,adaptor molecule,Aim2,and NOD-like receptor 4,increased at the mRNA level,and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1βprotein levels in male mice fed a long-term HFD.Male mice on HFD had increasedα-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis.In contrast,female mice displayed only elevated triglyceride levels,steatosis,and no fibrosis.CONCLUSION:Our data indicate gender differences in NASH.Male mice fed a long-term HFD display steatohepatitis and inflammasome activation,whereas female mice have steatosis without inflammation.展开更多
BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for rel...BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.展开更多
AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided in...AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet(HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic mi R-192-5 p and stearoyl-Co A desaturase 1(SCD-1) levels were measured. Mi R-192-5 p mimic and inhibitor and SCD-1 si RNA were transfected into Huh7 cells exposed to palmitic acid(PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays.RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic mi R-192-5 p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection(P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of mi R-192-5 p and SCD-1 protein levels, respectively(P < 0.01). Transfection with mi R-192-5 p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively(P < 0.01). Luciferase activity was suppressed and enhanced by mi R-192-5 p mimic and inhibitor, respectively, in wild-type SCD-1(P < 0.01) but not in mutant SCD-1. Mi R-192-5 p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 si RNA transfection abrogated the lipid deposition aggravated by mi R-192-5 p inhibitor(P < 0.01).CONCLUSION This study demonstrates that mi R-192-5 p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.展开更多
Objective The aim of this study was to investigate the energy deposition in the target area of high intensity focused ultrasound(HIFU) with ultrasound-guided intra-hysteromyoma injection of ethyl alcohol absolute Meth...Objective The aim of this study was to investigate the energy deposition in the target area of high intensity focused ultrasound(HIFU) with ultrasound-guided intra-hysteromyoma injection of ethyl alcohol absolute Methods Eighty patients with hysteromyomas were randomly divided into two groups: group HIFU(group H) and group HIFU combined with ultrasound-guided intra-hysteromyoma injectionn of ethyl alcohol absolute(group E + H). Patients in group E + H received an ultrasound-guided injection of absolute ethyl alcohol 1 h before HIFU treatment. The irradiation time, irradiation dose, energy efficiency factor(radiation energy required for ablation of a myoma per unit of volume), grey variation, pain score, and adverse reactions were compared between the two groups. An independent sample t-test was used with a twotailed P-value of < 0.05.Results The irradiation time, irradiation dose, and energy efficiency factor were significantly lower in group E + H than those in group H(P < 0.05). The hysteromyomas of patients in group E+H appeared as dominantly hyperechoic masses, and those of patients in group H appeared as hyperechoic tissue(nonmass). The incidence of adverse reactions and pain score were higher in group H than those in group E + H(P < 0.05).Conclusion Ultrasound-guided intra-hysteromyoma injection of ethyl alcohol absolute can enhance the energy deposition of HIFU in the uterine fibroids, improve the treatment efficiency, shorten the treatment time, reduce the treatment dose, and reduce the pain and complications for the patients.展开更多
文摘In order to increase activity of Cu Fe catalyst and use the mixture of nitrogen and hydrogen directly for preparation of high alcohols by reducing fatty acid esters, rare earths were used to modify the catalyst. Experiments show that yield of high alcohols increases by 3% as 1% Sm 2O 3 is added to the catalyst when the reduction is carried out under pure hydrogen. The yield greatly decreases when the reduction is carried out under the mixture of hydrogen and nitrogen. Catalysts activities modified by Y and Nd can be evidently improved and even enhanced. The yields increase by 33% and 29% when 1% Y 2O 3 and 1% Nd 2O 3 are added to the catalyst, respectively.
基金Supported by National Institute of Health,No.NCI-3R01CA121249-08S1,NCCIH-K99AT009206 and No.NCI-1R21CA191966
文摘BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, successful treatment options are limited. One of the main barriers to finding safe and effective drugs for long-term use in NAFLD is the fast initiation and progression of disease in the available preclinical models. Therefore, we are in need of preclinical models that (1) mimic the human manifestation of NAFLD and (2) have a longer progression time to allow for the design of superior treatments. AIM To characterize a model of prolonged high-fat diet (HFD) feeding for investigation of the long-term progression of NAFLD. METHODS In this study, we utilized prolonged HFD feeding to examine NAFLD features in C57BL/6 male mice. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 80 wk to promote obesity (Old-HFD group, n = 18). A low-fat diet (LFD)(14% fat, 32% protein, and 54% carbohydrate) was administered for the same duration to age-matched mice (Old-LFD group, n = 15). An additional group of mice was maintained on the LFD (Young-LFD, n = 20) for a shorter duration (6 wk) to distinguish between age-dependent and age-independent effects. Liver, colon, adipose tissue, and feces were collected for histological and molecular assessments.RESULTS Prolonged HFD feeding led to obesity and insulin resistance. Histological analysis in the liver of HFD mice demonstrated steatosis, cell injury, portal and lobular inflammation and fibrosis. In addition, molecular analysis for markers of endoplasmic reticulum stress established that the liver tissue of HFD mice have increased phosphorylated Jnk and CHOP. Lastly, we evaluated the gut microbial composition of Old-LFD and Old-HFD. We observed that prolonged HFD feeding in mice increased the relative abundance of the Firmicutes phylum. At the genus level, we observed a significant increase in the abundance of Adercreutzia, Coprococcus, Dorea, and Ruminococcus and decreased relative abundance of Turicibacter and Anaeroplasma in HFD mice. CONCLUSION Overall, these data suggest that chronic HFD consumption in mice can mimic pathophysiological and some microbial events observed in NAFLD patients.
文摘Introduction: Alcohol drinking and risky sexual practices have become serious public health problem among teenagers and young adults globally, including many developing countries. The available reports are sparse, especially there is a lack of recent and representative data for high school students in developing countries including Ethiopia. The aim of this study was to estimate the prevalence, identify determinants, and examine the association of alcohol drinking with sexual practices among high school students in Addis Ababa, capital city of Ethiopia. Methods: School based cross sectional study was conducted from November to December 2010. Multivariate logistic regression analysis was used to determine the association between students’ background characteristics and alcohol use, and alcohol use and sexual practices. Results: Among 2551 students surveyed, lifetime and current (past month) alcohol drinking was reported by 1166 (45.7%) and 676 (26.5%) students, respectively. Having sexual intercourse at least once in their lifetime was reported by 412 (16.2%) with151 (5.9%) of them being sexually active during a month prior to the survey. Having multiple sexual partners (52.5%), drinking alcohol before sexual intercourse (26.4%), and having sexual intercourse without the use of condom (47.3%) were also common among sexually active students. In adjusted logistic regression model, age (18 and 19 and older), living with 2 parents, getting pocket money, having alcohol drinking friends and attending general secondary school (grade 9-10) were positive predictors of current alcohol drinking. Nergative predictors of current alcohol drinking were being Protestant Christian and living with relatives or siblings. Conclusion: Alcohol drinking before sexual intercourse was a major problem among high school students in Addis Ababa, Ethiopia. Male gender, older age and higher school grade, friends influence, religious affiliation, living with parents and getting pocket money were significant predictors of current alcohol drinking. Educating about substance use and risky sexual behaviors, engaging students in extracurricular activities and restrict access to alcohol to high school students may help in solution of these problems on a local scale.
基金the National Natural Science Foundation of China,No.81660596the National Natural Science Foundation of China,No.81760733+2 种基金the Science and Technology Project of Yunnan China,No.2017FF117-013the Science and Technology Project of Yunnan China,No.2016FD050the Application and Basis Research Project of Yunnan China,No.201801CH00227
文摘BACKGROUND Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for therapy of nonalcoholic fatty liver disease(NAFLD).Polygonatum kingianum(PK)has been traditionally used in China as a medicinal and nutritional ingredient for centuries and can alleviate high-fat diet(HFD)-induced NAFLD by promoting mitochondrial functions.To date,the underlying molecular mechanism of PK for treating mitochondrial dysfunctions and thus alleviating NAFLD remains unclear.AIM To identify the molecular mechanism behind the mitochondrial regulatory action of PK against HFD-induced NAFLD in rats.METHODS NAFLD model was induced in rats with HFD.The rats were intragastrically administered PK(4 g/kg per day)for 14 wk.Metabolites in hepatic mitochondrial samples were profiled through ultra-high performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to find the potential biomarkers and metabolic pathways.RESULTS PK significantly restored the metabolites’levels in the mitochondrial samples.Ten potential biomarkers were identified in the analyzed samples.These biomarkers are involved in riboflavin metabolism.CONCLUSION PK can alleviate HFD-induced NAFLD by regulating the riboflavin metabolism and further improving the mitochondrial functions.Thus,PK is a promising mitochondrial regulator/nutrient for alleviating NAFLD-associated diseases.
基金These projects No. 39880003 and 20175016 were supported by the National Natural Science Foundation of China.
文摘The contributions of tetrahydrofurfuryl alcohol (THFA) and polyethylene glycol (PEG) to the renatured efficiency of a-chymotrypsin were investigated and compared with each other. The maximum increments of bioactivity recovery of a-Chy were found to be 25.1% for THFA, 10.4% for PEG, respectively. The experimental results indicated that the denaturant solution containing THFA contributed more to the renaturation of a-Chy in high performance hydrophobic interaction chromatography (HPHIC) than that containing PEG, when the concentration of THFA was 3.2%, the bioactivity recovery of a-Chy is the highest.
文摘为了探究草菇子实体多肽(Volvariella volvacea fruit body polypeptides,VVFP)对模型小鼠急性酒精肝预防作用及肠道菌群的影响,以先前获得的VVFP(分子质量1~3 kDa)为材料灌胃小鼠,将小鼠随机分为空白组、模型组、阳性对照组、多肽低剂量组、多肽中剂量组、多肽高剂量组,比较各组小鼠的血清和肝脏指标以及组织病理切片,利用16S rDNA基因高通量测序分析各样品中微生物菌群的生物多样性以及在门和属水平上的相对丰度。结果表明,与模型组相比,VVFP能够极显著降低血清中甘油三酯、总胆固醇、谷丙转氨酶、谷草转氨酶水平和肝脏中丙二醛的含量,并且降低肿瘤坏死因子-α、白细胞介素-6炎症因子水平,同时明显提高肝脏中乙醇脱氢酶、总超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。16S rDNA基因高通量测序结果表明,VVFP可以使小鼠肠道菌群中α多样性的Chao1指数和Observed_species指数明显降低,Shannon指数升高,并可通过调节拟杆菌门、厚壁菌门、链霉菌属、乳酸杆菌属和弧菌属的丰度从而减轻小鼠肝脏的损伤程度。综上,VVFP可以减轻酒精引起的肝损伤,本研究可为多肽在功能食品领域的应用提供理论参考。
基金Supported by National Institutes of Health Grant,No.DK075635
文摘AIM:To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis(NASH),which has been a challenge.METHODS:In this study,we used a high fat diet(HFD)feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States.We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively,and evaluated the extent of liver damage,steatosis,and inflammasome activation.Our methods included histopathological analysis to assess liver damage and steatosis,which involved H and E and oil-red-o staining;biochemical studies to look at ALT and triglyceride levels;RNA analysis using quantitative polymerase chain reaction;and cytokine analysis,which included the enzyme-linked immunosorbent assay method to look at interleukin(IL)-1βand tumor necrosis factor-α(TNFα)levels.Furthermore,at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests(ITT)and glucose tolerance tests.RESULTS:There was no insulin resistance,steatosis,or inflammasome activation at 6 wk.In contrast,at16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male,but not female mice.In males,elevated alanine aminotransferase and triglyceride levels,indicated liver damage and steatosis,respectively.Increased liver TNFαand monocyte chemoattractant protein-1 mRNA and protein,correlated with steatohepatitis.The inflammasome components,adaptor molecule,Aim2,and NOD-like receptor 4,increased at the mRNA level,and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1βprotein levels in male mice fed a long-term HFD.Male mice on HFD had increasedα-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis.In contrast,female mice displayed only elevated triglyceride levels,steatosis,and no fibrosis.CONCLUSION:Our data indicate gender differences in NASH.Male mice fed a long-term HFD display steatohepatitis and inflammasome activation,whereas female mice have steatosis without inflammation.
基金Supported by the Innovation Fund Denmark,Tolbol KS,No.5016-00168B
文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.
基金Supported by National Key R&D Program of China No.2017YFC0908900National Key Basic Research Project,No.2012CB517501National Natural Science Foundation of China,No.81470840 and No.81600464
文摘AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet(HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic mi R-192-5 p and stearoyl-Co A desaturase 1(SCD-1) levels were measured. Mi R-192-5 p mimic and inhibitor and SCD-1 si RNA were transfected into Huh7 cells exposed to palmitic acid(PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays.RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic mi R-192-5 p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection(P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of mi R-192-5 p and SCD-1 protein levels, respectively(P < 0.01). Transfection with mi R-192-5 p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively(P < 0.01). Luciferase activity was suppressed and enhanced by mi R-192-5 p mimic and inhibitor, respectively, in wild-type SCD-1(P < 0.01) but not in mutant SCD-1. Mi R-192-5 p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 si RNA transfection abrogated the lipid deposition aggravated by mi R-192-5 p inhibitor(P < 0.01).CONCLUSION This study demonstrates that mi R-192-5 p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.
文摘Objective The aim of this study was to investigate the energy deposition in the target area of high intensity focused ultrasound(HIFU) with ultrasound-guided intra-hysteromyoma injection of ethyl alcohol absolute Methods Eighty patients with hysteromyomas were randomly divided into two groups: group HIFU(group H) and group HIFU combined with ultrasound-guided intra-hysteromyoma injectionn of ethyl alcohol absolute(group E + H). Patients in group E + H received an ultrasound-guided injection of absolute ethyl alcohol 1 h before HIFU treatment. The irradiation time, irradiation dose, energy efficiency factor(radiation energy required for ablation of a myoma per unit of volume), grey variation, pain score, and adverse reactions were compared between the two groups. An independent sample t-test was used with a twotailed P-value of < 0.05.Results The irradiation time, irradiation dose, and energy efficiency factor were significantly lower in group E + H than those in group H(P < 0.05). The hysteromyomas of patients in group E+H appeared as dominantly hyperechoic masses, and those of patients in group H appeared as hyperechoic tissue(nonmass). The incidence of adverse reactions and pain score were higher in group H than those in group E + H(P < 0.05).Conclusion Ultrasound-guided intra-hysteromyoma injection of ethyl alcohol absolute can enhance the energy deposition of HIFU in the uterine fibroids, improve the treatment efficiency, shorten the treatment time, reduce the treatment dose, and reduce the pain and complications for the patients.
