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The current trend and challenges of developing red yeast rice-based food supplements for hypercholesterolemia

Journal of Future Foods 2023年第4期3卷 312-329页

作者： Gong Chen Wanbo Chen Jinhong Xu Guodong Ma Xinge Hu Guoxun Chen department of internal medicine University of Texas Southwestern Medical Center at DallasDallas 75390USA Clinical School of Chinese medicine Hubei University of Chinese MedicineWuhan 430022China College of Pharmacy South-Central University for NationalitiesWuhan 430074China department of nutrition University of Tennessee at KnoxvilleKnoxville 37996USA

Hypercholesterolemia is a risk factor of cardiovascular diseases,which have been managed using statin *** yeast rice(RYR)as a traditional food in the Eastern Asia countries has anti-hyperlipidemia ***,a variety of food supplement products containing RYR have been developed to lower blood cholesterol,which is attributed to the presence of monacolins,especially monacolin K(lovastatin,a statin drug).This review was aimed to summarize the clinical trials using RYR products to investigate their effects on lipid profiles in *** articles of human clinical trials were retrieved from PubMed and discussed *** showed that RYR and its extracts have been included in commercially available products alone and in combinations with various other materials,which include bioactive compounds such as coenzyme Q10 and berberine,vitamins,extracts from other plants such as phytosterols,polyunsaturated fatty acids or even *** durations of the trials ranged from 4 weeks to 60 *** content of monacolin K ranged from 0.32 mg/pack to 10 mg/*** data of these human clinical trials demonstrated that these RYR supplement products were sufficient to reduce blood cholesterol in different ***,the inclusions of certain materials might not have additive ***,studies including a lovastatin only positive control group with the equivalent dose as that of monacolin K in the RYR products remain to be ***,variations of monacolin K contents and presence of toxic citrinin are still ***,bioactivities of other components in RYR should be investigated as *** future studies will certainly help to fully explore the potentials of this traditional food in the combat against cardiovascular and other metabolic diseases.

关键词： Cardiovascular diseases Cholesterol human clinical trials Food supplement Hypercholesterolemia Monacolins Red yeast rice

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New insights into the role of Lith genes in the formation of cholesterol-supersaturated bile

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Liver Research 2017年第1期1卷 42-53页

作者： Helen H.Wang Tiangang Li Piero Portincasa David A.Ford Brent A.Neuschwander-Tetri Patrick Tso David Q-H.Wang department of internal medicine Division of Gastroenterology and HepatologySaint Louis University School of MedicineSt.LouisMOUSA department of Pharmacology Toxicology and TherapeuticsKansas University Medical CenterKansas CityKSUSA Clinica Medica“A.Murri” Department of Biomedical Sciences and Human OncologyUniversity of Bari“Aldo Moro”Medical SchoolBariItaly department of Biochemistry and Molecular Biology Saint Louis University School of MedicineSt.LouisMOUSA department of Pathology and Laboratory medicine University of Cincinnati College of MedicineCincinnatiOHUSA

Cholesterol gallstone formation represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is *** bile is mainly caused by persistent hepatic hypersecretion of biliary cholesterol and sustained cholesterol-supersaturated bile is an essential prerequisite for the precipitation of solid cholesterol monohydrate crystals and the formation of cholesterol *** metabolic determinants of the supply of hepatic cholesterol molecules that are recruited for biliary secretion are dependent upon the input-output balance of cholesterol and its catabolism in the *** sources of cholesterol for hepatic secretion into bile have been extensively investigated;however,to what extent each cholesterol source contributes to hepatic secretion is still unclear both under normal physiological conditions and in the lithogenic *** it has been long known that biliary lithogenicity is initiated by hepatic cholesterol hypersecretion,the genetic mechanisms that cause supersaturated bile have not been defined *** of the Lith genes that determine hepatic cholesterol hypersecretion should provide novel insights into the primary genetic and pathophysiological defects for gallstone *** this review article,we focus mainly on the pathogenesis of the formation of supersaturated bile and gallstones from the viewpoint of genetics and pathophysiology.A better understanding of the molecular genetics and pathophysiology of the formation of cholesterol-supersaturated bile will undoubtedly facilitate the development of novel,effective,and noninvasive therapies for patients with gallstones,which would reduce the morbidity,mortality,and costs of health care associated with gallstones,a very prevalent liver disease worldwide.

关键词： Bile flow Bile acid Biliary secretion Lith gene Micelle Vesicle

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MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3

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National Science Review 2020年第3期7卷 671-685页

作者： Chuanyin Li Wenli Lu Liguang Yang Zhengwei Li Xiaoyi Zhou Rong Guo Junqi Wang Zhebao Wu Zhiya Dong Guang Ning Yujiang Shi Yinmin Gu Peng Chen Zijian Hao Tianting Han Meiqiang Yang Wei Wang Xuehui Huang Yixue Li Shan Gao Ronggui Hu department of Pediatrics Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine State Key Laboratory of Molecular Biology CAS Center for Excellence in Molecular Cell Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences CAS Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational BiologyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of Sciences College of Life Sciences Shanghai Normal University Center for Pituitary Tumor Ruijin Hospital Affiliated to Shanghai Jiao Tong University Shanghai Institute of Endocrine and metabolic diseases Shanghai Key Laboratory for Endocrine Tumors and E-Institute for EndocrinologyRuijin Hospital Shanghai Jiao Tong University School of Medicine division of Endocrinology Diabetes and Hypertension Department of Medicine Brigham and Women's Hospital Harvard Medical School CAS Key Laboratory of Bio-medical Diagnostics Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences Cancer Center Shanghai Tenth People's HospitalSchool of Medicine Tongji University

Central precocious puberty(CPP) refers to a human syndrome of early puberty initiation with characteristic increase in hypothalamic production and release of gonadotropin-releasing hormone(Gn RH). Previously, loss-of-function mutations in human MKRN3, encoding a putative E3 ubiquitin ligase, were found to contribute to about 30% of cases of familial CPP. MKRN3 was thereby suggested to serve as a ‘brake’ of mammalian puberty onset, but the underlying mechanisms remain as yet ***, we report that genetic ablation of Mkrn3 did accelerate mouse puberty onset with increased production of hypothalamic Gn RH1. MKRN3 interacts with and ubiquitinates MBD3, which epigenetically silences GNRH1 through disrupting the MBD3 binding to the GNRH1 promoter and recruitment of DNA demethylase TET2. Our findings have thus delineated a molecular mechanism through which the MKRN3–MBD3 axis controls the epigenetic switch in the onset of mammalian puberty.

关键词： ubiquitin MKRN3 DNA methylation MBD3 DNA demethylase central precocious puberty

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Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic diseases International 2024年第3期23卷 241-248页

作者： Chao Sun George Boon-Bee Goh Wan-Cheng Chow Wah-Kheong Chan Grace Lai-Hung Wong Wai-Kay Seto Yi-Hsiang Huang Han-Chieh Lin I-Cheng Lee Hye Won Lee Seung Up Kim Vincent Wai-Sun Wong Jian-Gao Fan Center for Fatty Liver Disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China department of Gastroenterology&Hepatology Singapore General HospitalSingaporeSingapore Gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia department of medicine and Therapeutics and State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong KongChina department of medicine The University of Hong KongHong KongChina Institute of Clinical medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina division of Gastroenterology and Hepatology Taipei Veterans General HospitalTaipeiTaiwanChina Faculty of medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina department of internal medicine Yonsei University College of MedicineSeoulKorea

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic ***,the prevalence and risk factors for impaired renal function in patients with NAFLD remain *** objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD ***:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective *** fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 *** renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value ofmetabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of *** glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

关键词： Nonalcoholic fatty liver disease Impaired renal function Agile 3+ Agile 4 metabolic syndrome

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Pathogenic role of oxidative and nitrosative stress in primary biliary cirrhosis

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World Journal of Gastroenterology 2014年第19期20卷 5746-5759页

作者： Ignazio Grattagliano Giuseppe Calamita Tiziana Cocco David Q-H Wang Piero Portincasa Italian College of General Practitioners 50100 FlorenceBari 70124Italy department of Bioscience Biotechnologyand Biopharmaceutics"Aldo Moro" University Medical SchoolBari 70124Italy department of Basic Medical Science Neurosciencesand Sense Organs"Aldo Moro" University Medical SchoolBari 70124Italy department of internal medicine Division of Gastroenterology and HepatologySaint Louis University School of MedicineSt.LouisMO 63104United States Clinica Medica "A.Murri" Department of Biomedical Sciences and Human Oncology"Aldo Moro" University Medical SchoolBari 70124Italy

Primary biliary cirrhosis is a multifactor autoimmune disease characterized by hepatic and systemic manifestations,with immune system dysregulation and abnormalities in the hepatic metabolism of bile salts,lipids,and nutrients,as well as destruction of membrane lipids and mitochondrial *** oxidative and nitrosative stress are associated with ongoing manifestations of the *** particular,abnormalities in nitric oxide metabolism and thiol oxidation already occur at early stages,thus leading to the hypothesis that these biochemical events play a pathogenic role in primary biliary ***,the association of these metabolic abnormalities with the progression of the disease may indicate some biochemical parameters as early diagnostic markers of disease evolution,and may open up the potential for pharmacological intervention to inhibit intra-and extra-cellular stress events for resuming hepatocellular *** following paragraphs summarize the current knowledge by outlining molecular mechanisms of the disease related to these stress events.

关键词： Aquaporins Bile salts Chronic cholestasis Glutathione Mitochondria Nitrosothiols Nitrotyrosine Protein sulfhydryls Thioredoxin

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Fabricating 3-dimensional human brown adipose microtissues for transplantation studies

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Bioactive Materials 2023年第4期22卷 518-534页

作者： Ou Wang Li Han Haishuang Lin Mingmei Tian Shuyang Zhang Bin Duan Soonkyu Chung Chi Zhang Xiaojun Lian Yong Wang Yuguo Lei department of Chemical and Biomolecular Engineering University of Nebraska-LincolnNEUSA Biomedical Engineering Program University of Nebraska-LincolnNEUSA department of Biomedical Engineering Pennsylvania State UniversityPAUSA China Novartis Institutes for BioMedical Research Co. Ltd.BeijingChina department of Chemistry University of Nebraska-LincolnNEUSA Mary&Dick Holland Regenerative medicine Program and division of Cardiology Department of Internal MedicineUniversity of Nebraska Medical CenterOmahaNEUSA department of nutrition University of MassachusettsAmherstMAUSA School of Biological Science University of Nebraska-LincolnNEUSA Huck Institutes of the Life Sciences Pennsylvania State UniversityPAUSA

Transplanting cell cultured brown adipocytes(BAs)represents a promising approach to prevent and treat obesity(OB)and its associated metabolic disorders,including type 2 diabetes mellitus(T2DM).However,transplanted BAs have a very low survival rate in *** enzymatic dissociation during the harvest of fully differentiated BAs also loses significant *** is a critical need for novel methods that can avoid cell death during cell preparation,transplantation,and in ***,we reported that preparing BAs as injectable microtissues could overcome the *** found that 3D culture promoted BA differentiation and UCP-1 expression,and the optimal initial cell aggregate size was 100μ*** microtissues could be produced at large scales via 3D suspension assisted with a PEG hydrogel and could be *** microtissues could survive in vivo for long *** alleviated body weight and fat gain and improved glucose tolerance and insulin sensitivity in high-fat diet(HFD)-induced OB and T2DM *** microtissues impacted multiple organs,secreted protein factors,and influenced the secretion of endogenous *** our best knowledge,this is the first report on fabricating human BA microtissues and showing their safety and efficacy in T2DM *** proposal of transplanting fabricated BA microtissues,the microtissue fabrication method,and the demonstration of efficacy in T2DM mice are all *** results show that engineered 3D human BA microtissues have considerable advantages in product scalability,storage,purity,safety,dosage,survival,and efficacy.

关键词： Brown adipocyte Microtissue Transplantation Obesity Type 2 diabetes

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Vitamin d deficiency and metabolic syndrome:The joint effect on cardiovascular and all-cause mortality in the United States adults

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World Journal of Cardiology 2022年第7期14卷 411-426页

作者： Longjian Liu Saishi Cui Stella L Volpe Nathalie S May Deeptha Sukumar Rose Ann DiMaria-Ghalili Howard J Eisen department of Epidemiology and Biostatistics Dornsife School of Public HealthDrexel UniversityPhiladelphiaPA 19104United States department of human nutrition Foodsand ExerciseVirginia Polytechnic Institute and State UniversityBlacksburgVA 24061United States department of medicine College of MedicineDrexel UniversityPhiladelphiaPA 19102United States department of nutrition Sciences College of Nursing and Health ProfessionsDrexel UniversityPhiladelphiaPA 19102United States department of Graduate Nursing College of Nursing and Health ProfessionsDrexel UniversityPhiladelphiaPA 19102United States division of Cardiology Heart and Vascular InstitutePennsylvania State UniversityHersheyPA 17033United States

BACKGROUND The long-term impact of vitamin D deficiency and metabolic syndrome(MetS)on cardiovascular disease(CVD)and all-cause mortality are still a matter of *** To test the hypotheses that lower serum 25 hydroxyvitamin D[25(OH)D]concentrations(a marker of vitamin D level)and MetS have a long-term impact on the risk of CVD and all-cause mortality,and individuals with vitamin D deficiency can be identified by multiple *** A sample of 9094 adults,20 to 90 years of age,who participated in the Third National Health and nutrition Examination Survey(NHANES III,1988 to 1994)were followed through December 2015 was *** associations of serum 25(OH)D concentrations and MetS with CVD and all-cause mortality were analyzed longitudinally using Cox regression *** and regression tree(CART)for machine learning was applied to classify individuals with vitamin D *** Of 9094 participants,30%had serum 25(OH)D concentrations<20 ng/mL(defined as vitamin D deficiency),39%had serum 25(OH)D concentrations between 20 to 29 ng/mL(insufficiency),and 31%had serum 25(OH)D concentrations≥30 ng/mL(sufficiency).Prevalence of MetS was 28.4%.During a mean of 18 years follow-up,vitamin D deficiency and MetS were significantly associated with increased risk of CVD and all-cause *** with both vitamin D deficiency and MetS had the highest risk of CVD mortality(HR=1.77,95%CI:1.22-2.58)and all-cause mortality(HR=1.62,95%CI:1.26-2.09),followed by those with both vitamin D insufficiency and MetS for CVD mortality(HR=1.59,95%CI:1.12-2.24),and all-cause mortality(HR=1.41,95%CI:1.08-1.85).Meanwhile,vitamin D sufficiency significantly decreased the risk of CVD and all-cause mortality for those who even had *** the total study sample,CART analysis suggests that being non-Hispanic Black,having lower serum folate level,and being female were the first three predictors for those with serum 25(OH)D *** Vitamin D defic

关键词： Joint effect Serum 25 hydroxyvitamin D concentration metabolic syndrome Cardiovascular and all-cause mortality Cox model and machine learning

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Influence of Preservation Solutions and Bile on a human Bile Duct Epithelium Cell Line: An <i>In-Vitro</i>Study

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Open Journal of Organ Transplant Surgery 2012年第4期2卷 37-41页

作者： Philipp Stiegler Ursula Mayrhauser Sonja Koestenbauer Bettina Leber Katja Konrad Florian Iberer Karlheinz Tscheliessnigg Vanessa Stadlbauer division of internal medicine Department of Gastroenterology and Hepatology Medical University Graz division of Surgery Department for Transplantation Surgery Medical University Graz

Introduction: Bile duct complications are common after liver transplantation. The impact of preservation solution is unclear. Aim: We investigated the impact of different preservation solutions with and without diluted bile on a human biliary tract carcinoma cell line. Methods: The human biliary tree carcinoma cell line SK-ChA-1 was cultured with either medium or University of Wisconsin solution (UW), histidine-tryptophane-ketoglutarate (HTK) solution, Celsior or physiological saline for 6h, 10h or 12h at 6℃- 8℃ and metabolic activity was measured by a MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)-test immediately, after 12h or 24h. Cells were also incubated in combination with diluted porcine bile. Results: Immediately after cold storage of 6h HTK and UW decreased metabolic activity whereas Celsior increased metabolic activity after 10h or 12h of cold ischemia. After 12h or 24h no major differences were found any more. Incubation with bile in combination with HTK, Celsior or NaCl decreased metabolic activity, whereas UW abolished this effect. Conclusion: On a cellular level differences between preservation solutions were found, especially in combination with bile. Further studies are warranted to determine whether this results in clinically significant differences in biliary complications.

关键词： Organ Preservation Liver Transplantation Bile Duct Epithelium In Vitro

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Gut Microbiota: Physiology and Relationship with Inflammatory Bowel Disease

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Open Journal of Endocrine and metabolic diseases 2013年第7期3卷 283-292页

作者： Chun-Yu Lin Yeong-Jang Lin Hung-An Chen division of Allergy-Immunology-Rheumatology Department of Internal Medicine Chi Mei Medical Center Tainan Taiwan

The intestinal microbiota, which evolved over tens of thousands of years along with their human hosts, constitutes a complex and diverse ecosystem whose composition differs from person to person. Accumulating evidence indicates that commensal bacteria exert numerous beneficial physiological effects for humans, including nutrition, protection, metabolism, organ development and immunomodulation. However, mucosal immune responses to intestinal microflora require precise control to allow appropriate defense against potential pathogens but restrict the immune response to beneficial resident bacteria. The task of intestinal homeostasis is accomplished by epithelium and specialized immune system in the gastrointestinal tract. Alternation in the composition of the bacterial community, consisting of increased representation of harmful species or under presence of protective species, or dysbiosis has been linked to various chronic and inflammatory disorders, such as inflammatory bowel disease. An improved understanding of the underlying molecular mechanisms of host-microorganism interactions could bring new insights into onset and pathogenesis of several autoimmune diseases. This review will discuss physiologic properties of commensal microbiota and how dysregulated immune responses to them contribute to chronic mucosal inflammation.

关键词： Gut Microbiota: Physiology and Relationship with Inflammatory Bowel Disease

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Fatty acid oxidation-induced HIF-1α activation facilitates hepatic urate synthesis through upregulating NT5C2 and XDH

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Life Metabolism 2024年第5期3卷 17-31页

作者： Ningning Liang Xuan Yuan Lili Zhang Xia Shen Shanshan Zhong Luxiao Li Rui Li Xiaodong Xu Xin Chen Chunzhao Yin Shuyuan Guo Jing Ge Mingjiang Zhu Yongzhen Tao Shiting Chen Yongbing Qian Nicola Dalbeth Tony RMerriman Robert Terkeltaub Changgui Li Qiang Xia Huiyong Yin CAS Key Laboratory of nutrition Metabolismand Food SafetyShanghai Institute of Nutrition and HealthChinese Academy of Sciences(CAS)Shanghai 200031China University of Chinese Academy of Sciences Beijing 100049China department of Biomedical Sciences Jockey Club College of Veterinary Medicine and MedicineTung Biomedical Science CenterState Key Laboratory of Marine Pollution(SKLMP)The Shenzhen Research Institute and Futian Research InstituteCity University of Hong KongHong Kong 999077China Institute of metabolic diseases Qingdao UniversityQingdaoShandong 266003China Shandong Provincial Key Laboratory of metabolic diseases Qingdao Key Laboratory of GoutAffiliated Hospital of Qingdao University Medical CollegeQingdao UniversityQingdaoShandong 266071China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China department of medicine Faculty of Medical and Health SciencesUniversity of AucklandAuckland 1142New Zealand department of Biochemistry University of OtagoDunedin 9016New Zealand division of Clinical Immunology and Rheumatology University of Alabama at BirminghamBirminghamAlabama 35294United States VA San Diego Healthcare System San DiegoLa JollaCA 92037United States School of medicine University of California San DiegoLa JollaCA 92037United States

Dyslipidemia affects approximately half of all people with gout,and prior Mendelian randomization analysis suggested a causal role for elevated triglycerides in hyperuricemia(HU),but the underlying mechanisms remain *** hypothesize that dyslipi-demia promotes hepatic urate biosynthesis in HU and gout and fatty acid(FA)oxidation(FAO)drives this *** we devel-oped a targeted metabolomics to quantify major metabolites in purine metabolic pathway in the sera of a human cohort with HU,gout,and normaluricemic *** found that the levels of major purine metabolites and multiple FAs were significantly elevated in HU and gout groups compared to normouricemic controls,whereas hypoxathine showed opposite ***,the levels of multiple serum FAs were positively correlated with urate,xanthine,and inosine but negatively with hypoxanthine,which was also observed in a murine model of high-fat diet-induced *** a stable isotope-labeled metabolic flux assay,we discovered that exogenous hypoxanthine plays a key role in urate ***,FAO-induced hypoxia-inducible factor 1 alpha(HIF-1α)activation upregulated 5ʹ-nucleotidase II(NT5C2)and xanthine dehydrogenase(XDH)levels to facilitate hypox-anthine uptake from the blood to the liver and activation of urate *** findings were further supported by data in human hepatocytes and 50 paired serum and liver tissues from liver transplant ***,this study uncovers a mecha-nism by which FAO promotes hepatic urate synthesis by activating HIF-1α-NT5C2/XDH pathways,directly linking lipid metabo-lism to HU.

关键词： dyslipidemia hyperuricemia purine hypoxanthine metabolic flux

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