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| 1 | Th e role of ferroptosis in ionizing radiation-induced cell death and tumor suppression显示文摘Ferroptosis,a form of regulated cell death caused by lipid peroxidation,was recently identified as a natural tumor suppression mechanism.Here,we show that ionizing radiation(IR)induces ferroptosis in cancer cells.Mechanistically,IR induces not only reactive oxygen species(ROS)but also the expression of ACSL4,a lipid metabolism enzyme required for ferroptosis,resulting in elevated lipid peroxidation and ferroptosis.ACSL4 ablation largely abolishes IR-induced ferroptosis and promotes radioresistance.IR also induces the expression of ferroptosis inhibitors,including SLC7A11 and GPX4;as an adaptive response.IR-or KEAP1 deficiencyinduced SLC7A11 expression promotes radioresistance through inhibiting ferroptosis.Inactivating SLC7A11 or GPX4 with ferroptosis inducers(FINs)sensitizes radioresistant cancer cells and xenograft tumors to IR.Furthermore,radiotherapy induces ferroptosis in cancer patients,and increased ferroptosis correlates with better response and longer survival to radiotherapy in cancer patients.Our study reveals a previously unrecognized link between IR and ferroptosis and indicates that further exploration of the combination of radiotherapy and FINs in cancer treatment is warranted. | Guang Lei Yilei Zhang Pranavi Koppula Xiaoguang Liu Jie Zhang Steven HLin Jaffer AAjani Qin Xiao Zhongxing Liao Hui Wang Boyi Gan | 2020 | Cell Research2020，30，2： | 88 |
| 2 | Pathogenesis of alcoholic liver disease:Role of oxidative metabolism显示文摘Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases,resulting in fatty liver,alcoholic hepatitis,fibrosis/cirrhosis,and hepatocellular carcinoma(HCC).Although the pathogenesis of alcoholic liver disease(ALD)involves complex and still unclear biological processes,the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species(ROS)play a preeminent role in the clinical and pathological spectrum of ALD.Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes,leading to fat accumulation,fibrogenesis and activation of innate and adaptive immunity.Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis,decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase(AMPK)-dependent mechanism.AMPK activation by ROS modulates autophagy,which has an important role in removing lipid droplets.Acetaldehyde and aldehydes generated from lipid peroxidation induce collagensynthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells(HSCs).Furthermore,activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD.Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide(LPS)translocation by disrupting tight and adherent junctions in human colonic mucosa.Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration.In addition,alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver.Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells,and consequently alters allogenic antigen presentation.Finally,acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis,and they interfere with methylation,synthesis and repair of DNA,thereby increasing HCC susceptibility. | Elisabetta Ceni Tommaso Mello Andrea Galli | 2014 | World Journal of Gastroenterology2014，20，47： | 72 |
| 3 | Gut microbiota and host metabolism in liver cirrhosis显示文摘The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulatingthe activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probioticstreated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients. | Makoto Usami Makoto Miyoshi Hayato Yamashita | 2015 | World Journal of Gastroenterology2015，21，41： | 44 |
| 4 | The role of the gut microbiome and its metabolites in metabolic diseases显示文摘It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases,while in recent years,accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases,including obesity,type 2 diabetes,nonalcoholic fatty liver disease,cardiovascular disease and so on.Numerous microorganisms dwell in the gastrointestinal tract,which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances,thus acting as a link between the gut microbiome and its host.The gut microbiome is shaped by host genetics,immune responses and dietary factors.The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases.Therefore,targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future.This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic diseases.Furthermore,recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed. | Jiayu Wu Kai Wang Xuemei Wang Yanli Pang Changtao Jiang | 2021 | Protein & Cell2021，12，5： | 40 |
| 5 | Human gut microbiome: the second genome of human body显示文摘The human body is actually a super-organism that is composed of 10 times more microbial cells than our body cells.Metagenomic study of the human microbiome has demonstrated that there are 3.3 million unique genes in human gut,150 times more genes than our own genome,and the bacterial diversity analysis showed that about 1000 bacterial species are living in our gut and a majority of them belongs to the divisions of Firmicutes and Bacteriodetes.In addition,most people share a core microbiota that comprises 50–100 bacterial species when the frequency of abundance at phylotype level is not considered,and a core microbiome harboring more than 6000 functional gene groups is present in the majority of human gut surveyed till now.Gut bacteria are not only critical for regulating gut metabolism,but also important for host immune system as revealed by animal studies. | Baoli Zhu Xin Wang Lanjuan Li | 2010 | Protein & Cell2010，1，8： | 40 |
| 6 | Effect of early enteral combined with parenteral nutrition in patients undergoing pancreaticoduodenectomy显示文摘AIM:To investigate the effect of early enteral nutrition(EEN)combined with parenteral nutritional support in patients undergoing pancreaticoduodenectomy(PD).METHODS:From January 2006,all patients were given EEN combined with parenteral nutrition(PN)(EEN/PN group,n=107),while patients prior to this date were given total parenteral nutrition(TPN)(TPN group,n=67).Venous blood samples were obtained for a nutrition-associated assessment and liver function tests on the day before surgery and 6 d after surgery.The assessment of clinical outcome was based on postoperative complications.Follow-up for infectious and noninfectious complications was carried out for 30 d after hospital discharge.Readmission within 30 d afterdischarge was also recorded.RESULTS:Compared with the TPN group,a significant decrease in prealbumin(PAB)(P=0.023)was seen in the EEN/PN group.Total bilirubin(TB),direct bilirubin(DB)and lactate dehydrogenase(LDH)were significantly decreased on day 6 in the EEN/PN group(P=0.006,0.004 and 0.032,respectively).The rate of gradeⅠcomplications,gradeⅡcomplications and the length of postoperative hospital stay in the EEN/PN group were significantly decreased(P=0.036,0.028and 0.021,respectively),and no hospital mortality was observed in our study.Compared with the TPN group(58.2%),the rate of infectious complications in the EEN/PN group(39.3%)was significantly decreased(P=0.042).Eleven cases of delayed gastric emptying were noted in the TPN group,and 6 cases in the EEN/PN group.The rate of delayed gastric emptying and hyperglycemia was significantly reduced in the EEN/PN group(P=0.031 and P=0.040,respectively).CONCLUSION:Early enteral combined with PN can greatly improve liver function,reduce infectious complications and delayed gastric emptying,and shorten postoperative hospital stay in patients undergoing PD. | Xin-Hua Zhu Ya-Fu Wu Yu-Dong Qiu Chun-Ping Jiang Yi-Tao Ding | 2013 | World Journal of Gastroenterology2013，19，35： | 34 |
| 7 | Vascular endothelial dysfunction, cardiomyopathy a major mediator in diabetic cardiomyopathy显示文摘Diabetes mellitus is currently a major public health problem.A common complication of diabetes is cardiac dysfunction,which is recognized as a microvascular disease that leads to morbidity and mortality in diabetic patients.While ischemic events are commonly observed in diabetic patients,the risk for developing heart failure is also increased,independent of the severity of coronary artery disease and hypertension.This diabetes-associated clinical entity is considered a distinct disease process referred to as 'diabetic cardiomyopathy'.However,it is not clear how diabetes promotes cardiac dysfunction.Vascular endothelial dysfunction is thought to be one of the key risk factors.The impact of diabetes on the endothelium involves several alterations,including hyperglycemia,fatty acid oxidation,reduced nitric oxide (NO),oxidative stress,inflammatory activation,and altered barrier function. The current review provides an update on mechanisms that specifically target endothelial dysfunction,which may lead to diabetic cardiomyopathy. | Maura Knapp Xin Tu Rongxue Wu | 2019 | Acta Pharmacologica Sinica2019，40，1： | 34 |
| 8 | Carotenoid metabolism and regulation in horticultural crops显示文摘Carotenoids are a diverse group of pigments widely distributed in nature.The vivid yellow,orange,and red colors of many horticultural crops are attributed to the overaccumulation of carotenoids,which contribute to a critical agronomic trait for flowers and an important quality trait for fruits and vegetables.Not only do carotenoids give horticultural crops their visual appeal,they also enhance nutritional value and health benefits for humans.As a result,carotenoid research in horticultural crops has grown exponentially over the last decade.These investigations have advanced our fundamental understanding of carotenoid metabolism and regulation in plants.In this review,we provide an overview of carotenoid biosynthesis,degradation,and accumulation in horticultural crops and highlight recent achievements in our understanding of carotenoid metabolic regulation in vegetables,fruits,and flowers. | Hui Yuan Junxiang Zhang Divyashree Nageswaran Li Li | 2015 | Horticulture Research2015，2，1： | 32 |
| 9 | Cytological, physiological, and transcriptomic analyses of golden leaf coloration in Ginkgo biloba L显示文摘Ginkgo biloba is grown worldwide as an ornamental plant for its golden leaf color.However,the regulatory mechanism of leaf coloration in G.biloba remains unclear.Here,we compared G.biloba gold-colored mutant leaves and normal green leaves in cytological,physiological and transcriptomic terms.We found that chloroplasts of the mutant were fewer and smaller,and exhibited ruptured thylakoid membranes,indistinct stromal lamellae and irregularly arranged vesicles.Physiological experiments also showed that the mutant had a lower chlorophyll,lower flavonoid and higher carotenoid contents(especially lutein).We further used transcriptomic sequencing to identify 116 differentially expressed genes(DEGs)and 46 transcription factors(TFs)involved in chloroplast development,chlorophyll metabolism,pigment biosynthesis and photosynthesis.Among these,the chlorophyll biosynthesis-related PPO showed down-regulation,while chlorophyll degradation-related NYC/NOL had up-regulated expression in mutant leaves.Z-ISO,ZDS,and LCYE,which are involved in carotenoid biosynthesis were up-regulated.Quantitative real-time PCR(RT-qPCR)further confirmed the altered expression levels of these genes at three stages.The alteration of PPO and NYC/NOL gene expression might affect chlorophyll biosynthesis and promote degradation of chlorophyll b to chlorophyll a,while the up-regulated genes Z-ISO,ZDS and LCYE enhanced carotenoid accumulation.Consequently,changes in the ratio of carotenoids to chlorophylls were the main factors driving the golden leaf coloration in the mutant G.biloba. | Wei-xing Li Shun-bo Yang Zhaogeng Lu Zhi-chong He Yun-ling Ye Bei-bei Zhao Li Wang Biao Jin | 2018 | Horticulture Research2018，5，1： | 28 |
| 10 | Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock显示文摘The mixed venous-to-arterial carbon dioxide(CO_2)tension difference[P(v-a) CO_2]is the difference between carbon dioxide tension(PCO_2) in mixed venous blood(sampled from a pulmonary artery catheter) and the PCO_2 in arterial blood.P(v-a) CO_2 depends on the cardiac output and the global CO_2 production,and on the complex relationship between PCO_2 and CO_2 content.Experimental and clinical studies support the evidence that P(v-a) CO_2 cannot serve as an indicator of tissue hypoxia,and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO_2generated by the peripheral tissues.P(v-a) CO_2 can be replaced by the central venous-to-arterial CO_2 difference(△PCO_2),which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and,therefore,more easy to obtain at the bedside.Determining the △PCO_2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation(SCVO_2) > 70%associated with elevated blood lactate levels.Because high blood lactate levels is not a discriminatory factor in determining the source of that stress,an increased △PCO_2(> 6 mmHg)could be used to identify patients who still remain inadequately resuscitated.Monitoring the △PCO_2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and,thus,guiding the therapy.In this respect,it can aid to titrate inotropes to adjust oxygen delivery to CO_2 production,or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO_2 related to metabolic demand.The combination of P(v-a) CO_2 or △PCO_2 with oxygen-derived parameters through the calculation of the P(v-a) CO_2 or △PCO_2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism. | Jihad Mallat Malcolm Lemyze Laurent Tronchon Beno?t Vallet Didier Thevenin | 2016 | World Journal of Critical Care Medicine2016，5，1： | 25 |
| 11 | Molecular mechanosensors in osteocytes显示文摘Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and indirect ways. The mechanotransduction process in osteocytes is a complex but exquisite regulatory process between cells and their environment, between neighboring cells, and between different functional mechanosensors in individual cells. Over the past two decades, great efforts have focused on finding various mechanosensors in osteocytes that transmit extracellular mechanical signals into osteocytes and regulate responsive gene expression. The osteocyte cytoskeleton, dendritic processes, Integrin-based focal adhesions, connexin-based intercellular junctions, primary cilium, ion channels, and extracellular matrix are the major mechanosensors in osteocytes reported so far with evidence from both in vitro and in vitro studies. This review aims to give a systematic introduction to osteocyte mechanobiology, provide details of osteocyte mechanosensors, and discuss the roles of osteocyte mechanosensitive signaling pathways in the regulation of bone homeostasis. | Lei Qin Wen Liu Huiling Cao Guozhi Xiao | 2020 | Bone Research2020，8，2： | 24 |
| 12 | Sequencing of Cultivated Peanut, Arachis hypogaea, Yields Insights into Genome Evolution and Oil Improvement显示文摘Cultivated peanut (Arachis hypogaea) is an allotetraploid crop planted in Asia, Africa, and America for edible oil and protein. To explore the origins and consequences of tetraploidy, we sequenced the allotetraploid A. hypogaea genome and compared it with the related diploid Arachis duranensis and Arachis ipaensis genomes. We annotated 39 888 A-subgenome genes and 41 526 B-subgenome genes in allotetraploid peanut. The A. hypogaea subgenomes have evolved asymmetrically, with the B subgenome resembling the ancestral state and the A subgenome undergoing more gene disruption, loss, conversion, and transposable element proliferation, and having reduced gene expression during seed development despite lacking genome-wide expression dominance. Genomic and transcriptomic analyses identified more than 2 500 oil metabolism-related genes and revealed that most of them show altered expression early in seed development while their expression ceases during desiccation, presenting a comprehensive map of peanut lipid biosynthesis. The availability of these genomic resources will facilitate a better understanding of the complex genome architecture, agronomically and economically important genes, and genetic improvement of peanut. | Xiaoping Chen Qing Lu Hao Liu Jianan Zhang Yanbin Hong Haofa Lan Haifen Li Jinpeng Wang Haiyan Liu Shaoxiong Li Manish K.Pandey Zhikang Zhang Guiyuan Zhou Jigao Yu Guoqiang Zhang Jiaqing Yuan Xingyu Li Shijie Wen Fanbo Meng Shanlin Yu Xiyin Wang Kadambot H.M.Siddique Zhong-Jian Liu Andrew H.Paterson Rajeev K.Varshney Xuanqiang Liang | 2019 | Molecular Plant2019，12，7： | 23 |
| 13 | The Reference Genome Sequence of Scutellaria baicalensis Provides Insights into the Evolution of Wogonin Biosynthesis显示文摘Scutellaria baicalensis Georgi is important in Chinese traditional medicine where preparations of dried roots,'Huang Qin,' are used for liver and lung complaints and as complementary cancer treatments. We report a high-quality reference genome sequence for S. baicalensis where 93% of the 408.14-Mb genome has been assembled into nine pseudochromosomes with a super-N50 of 33.2 Mb. Comparison of this sequence with those of closely related species in the order Lamiales, sesamum indicum and Salvia splendens,revealed that a specialized metabolic pathway for the synthesis of 4'-deoxyflavone bioactives evolved in the genus Scu-tellaria. We found that the gene encoding a specific cinnamate coenzyme A ligase likely obtained its newfunc- tion following recent mutations, and that four genes encoding enzymes in the 4'-deoxyflavone pathway are present as tandem repeats in the genome of S. baicalensis. Further analyses revealed that gene duplications, segmental duplication, gene amplification, and point mutations coupled to gene neo- and subfunctionaliza-tions were involved in the evolution of 4'-deoxyflavone synthesis in the genus Scutellaria. Our study not only provides significant insight into the evolution of specific flavone biosynthetic pathways in the mint family, Lamiaceae, but also will facilitate the development of tools for enhancing bioactive productivity by metabolic engineering in microbes or by molecular breeding in plants. The reference genome of S. baicalensis is also useful for improving the genome assemblies for other members of the mint family and offers an important foundation for decoding the synthetic pathways of bioactive compounds in medicinal plants. | Qing Zhao Jun Yang Meng-Ying Cui Jie Liu Yumin Fang Mengxiao Yan Wenqing Qiu Huiwen Shang Zhicheng Xu Reheman Yidiresi Jing-Ke Weng Tomas Pluskal Marielle Vigouroux Burkhard Steuernagel Yukun Wei Lei Yang Yonghong Hu Xiao-Ya Chen Cathie Martin | 2019 | Molecular Plant2019，12，7： | 23 |
| 14 | Expert consensus on the use of human serum albumin in critically ill patients显示文摘Introduction Human serum albumin(HSA)is a non-glycosylated,negatively charged,single-chain polypeptide composed of 585 amino acid residues with a relative molecular mass of 66.438 kD.It is synthesized by the liver at a rate of approximately 200 mg·kg^(-1)·day^(-1),with a half-life of 21 days,and subjected to catabolism in the muscles,liver,and kidneys at a rate of 4%per day.[1]Albumin,accounting for 60%of the total plasma protein,has various physiological functions,[2]such as maintaining 70%to 80%of effective plasma colloid osmotic pressure,coordinating vascular endothelial integrity,anti-oxidant and anti-inflammatory activities,maintaining the acidbase balance,and participating in the transport,distribution,and metabolism of a variety of endogenous and exogenous substances. | Yue-Tian Yu Jiao Liu Bo Hu Rui-Lan Wang Xiang-Hong Yang Xiu-Ling Shang Gang Wang Chang-Song Wang Bai-Ling Li Ye Gong Sheng Zhang Xin Li Lu Wang Min Shao Mei Meng Feng Zhu You Shang Qiang-Hong Xu Zhi-Xiong Wu De-Chang Chen | 2021 | Chinese Medical Journal2021，，14： | 22 |
| 15 | Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats via Activation of SIRT3/AMPK/ACC Pathway显示文摘This study aimed to verify the effects of berberine(BBR)on the fat metabolism proteins involved in the sirtuin 3(SIRT3)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)pathway in the liver tissues of rats with high-fat diet(HFD)-induced non-alcoholic fatty liver disease(NAFLD).Forty-eight rats were randomly divided into the normal control(NC)group,HFD group or BBR group,with 16 rats in each group.After 8 and 16 weeks of treatment,serum and liver samples were collected.Subsequently,body parameters,biochemical parameters and liver pathology were examined.The expression levels of proteins involved in the SIRT3/AMPK/ACC pathway in the liver were detected by Western blotting.After 8 and 16 weeks of a HFD,the successful establishment of rat models with different degrees of NAFLD was confirmed by hematoxylin and eosin(H&E)and Oil Red O staining.NAFLD rat models exhibited obesity and hyperlipidemia,and the protein expression levels of SIRT3,p-AMPK.p-ACC,and CPT-1A in the liver were significantly decreased compared to those in the NC group.The concurrent administration of BBR with the HFD effectively improved serum and liver lipid profiles and ameliorated liver injury.Furthermore,the protein expression levels of SIRT3,p-AMPK,p-ACC,and CPT-1 A in the liver were significantly increased in the BBR group as compared with those in the HFD group.In conclusion,our data suggest that the mechanism by which BBR ameliorates HFD-induced hepatic steatosis may be related to the activation of the SIRT3/AMPK/ACC pathway in the liver. | Yu-pei ZHANG Yuan-jun DENG Kai-rui TANG Run-sen CHEN Shu LIANG Yin-ji LIANG Li HAN Ling JIN Zi-en LIANG Yan-ning CHEN Qin-he YANG | 2019 | Current Medical Science2019，39，1： | 21 |
| 16 | PBPK modeling and simulation in drug research and development显示文摘Physiologically based pharmacokinetic(PBPK) modeling and simulation can be used to predict the pharmacokinetic behavior of drugs in humans using preclinical data.It can also explore the effects of various physiologic parameters such as age,ethnicity,or disease status on human pharmacokinetics,as well as guide dose and dose regiment selection and aid drug–drug interaction risk assessment.PBPK modeling has developed rapidly in the last decade within both the field of academia and the pharmaceutical industry,and has become an integral tool in drug discovery and development.In this mini-review,the concept and methodology of PBPK modeling are briefly introduced.Several case studies were discussed on how PBPK modeling and simulation can be utilized through various stages of drug discovery and development.These case studies are from our own work and the literature for better understanding of the absorption,distribution,metabolism and excretion(ADME) of a drug candidate,and the applications to increase efficiency,reduce the need for animal studies,and perhaps to replace clinical trials.The regulatory acceptance and industrial practices around PBPK modeling and simulation is also discussed. | Xiaomei Zhuang Chuang Lu | 2016 | Acta Pharmaceutica Sinica B2016，6，5： | 21 |
| 17 | The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals显示文摘Metabolic diseases are the most common and rapidly growing health issues worldwide.The massive population-based human genetics is crucial for the precise prevention and intervention of metabolic disorders.The China Metabolic Analytics Project(ChinaMAP)is based on cohort studies across diverse regions and ethnic groups with metabolic phenotypic data in China.Here,we describe the centralized analysis of the deep whole genome sequencing data and the genetic bases of metabolic traits in 10,588 individuals from the ChinaMAP.The frequency spectrum of variants,population structure,pathogenic variants and novel genomic characteristics were analyzed.The individual genetic evaluations of Mendelian diseases,nutrition and drug metabolism,and traits of blood glucose and BMI were integrated.Our study establishes a large-scale and deep resource for the genetics of East Asians and provides opportunities for novel genetic discoveries of metabolic characteristics and disorders. | Yanan Cao Lin Li Min Xu Zhimin Feng Xiaohui Sun Jieli Lu Yu Xu Peina Du Tiange Wang Ruying Hu Zhen Ye Lixin Shi Xulei Tang Li Yan Zhengnan Gao Gang Chen Yinfei Zhang Lulu Chen Guang Ning Yufang Bi Weiqing Wang The ChinaMAP Consortium | 2020 | Cell Research2020，30，9： | 20 |
| 18 | Fatty liver diseases,bile acids,and FXR显示文摘The prevalence of nonalcoholic fatty liver disease(NAFLD) worldwide has increased at an alarming rate,which will likely result in enormous medical and economic burden.NAFLD presents as a spectrum of liver diseases ranging from simple steatosis,nonalcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and even to hepatocellular carcinoma(HCC).A comprehensive understanding of the mechanism(s) of NAFLD-to-NASH transition remains elusive with various genetic and environmental susceptibility factors possibly involved.An understanding of the mechanism may provide novel strategies in the prevention and treatment to NASH.Abnormal regulation of bile acid homeostasis emerges as an important mechanism to liver injury.The bile acid homeostasis is critically regulated by the farnesoid X receptor(FXR) that is activated by bile acids.FXR has been known to exert tissue-specific effects in regulating bile acid synthesis and transport.Current investigations demonstrate FXR also plays a principle role in regulating lipid metabolism and suppressing inflammation in the liver.Therefore,the future determination of the molecular mechanism by which FXR protects the liver from developing NAFLD may shed light to the prevention and treatment of NAFLD. | Yan Zhu Hongxia Liu Min Zhang Grace L.Guo | 2016 | Acta Pharmaceutica Sinica B2016，6，5： | 20 |
| 19 | Linking uric acid metabolism to diabetic complications显示文摘Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted. | Akifumi Kushiyama Kentaro Tanaka Shigeko Hara Shoji Kawazu | 2014 | World Journal of Diabetes2014，5，6： | 19 |
| 20 | Effect of emodin and sandostatin on metabolism of eicosanoids in acute necrotizing pancreatitis显示文摘INTRODUCTIONIn order to study the therapeutic mechanisms ofemodin,an extract of Rhubarb (Rhizoma et RadixRhei,a traditional Chinese herbal medicine),andsandostatin in the treatment of acute necrotizingpancreatitis (ANP),we used the two drugs in ratmodels of the disease and observed the changes ofplasma thromboxane-2(TXB2),6-keto-prostaglandin F1α(6-keto-PGF1α)and prostaglandinE2(PEG2). | Jian Xin Wu Jia Yu Xu Yao Zong Yuan | 2000 | World Journal of Gastroenterology2000，6，2： | 19 |
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