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Prostaglandin E2 receptor EP3 regulates both adipogenesis and lipolysis in mouse white adipose tissue

Journal of Molecular Cell Biology 2016年第6期8卷 518-529页

作者： Hu Xu Jia-Lin Fu Yi-Fei Miao Chun-Jiong Wang Qi-Fei Han Sha Li Shi-Zheng Huang Sheng-Nan Du Yu-Xiang Qiu Ji-Chun Yang Jan-Ake Gustafsson Richard MBreyer Feng Zheng Nan-Ping Wang Xiao-Yan Zhang You-Fei Guan Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China center for Nuclear Receptors and Cell Signaling Department of Biology and BiochemistryUniversity of HoustonHoustonTX 77204USA Department of Veterans Affairs Tennessee Valley Health Authorityand Department of MedicineVanderbilt University Medical CenterNashvilleTN 37232USA Advanced Institute for medical Sciences Dalian Medical UniversityDalian 116044China Department of Physiology AstraZeneca–Shenzhen University Joint Institute of NephrologyShenzhen University Health Science CenterShenzhen 518060China

Among the four prostaglandin E2 receptors,EP3 receptor is the one most abundantly expressed in white adipose tissue(WAT).The mouse EP3 gene gives rise to three isoforms,namely EP3α,EP3β,and EP3γ,which differ only at their C-terminal *** date,functions of EP3 receptor and its isoforms in WAT remain incompletely *** this study,we found that the expression of all EP3 isoforms were downregulated in WAT of both db/db and high-fat diet-induced obese *** ablation of three EP3 receptor isoforms(EP3^(−/−)mice)or EP3αand EP3γisoforms with EP3βintact(EP3βmice)led to an obese phenotype with increased food intake,decreased motor activity,reduced insulin sensitivity,and elevated serum *** the differentiation of preadipocytes and mouse embryonic fibroblasts to adipocytes was markedly facilitated by either pharmacological blockade or genetic deletion/inhibition of EP3 receptor via the cAMP/PKA/PPARγpathway,increased adipogenesis may contribute to obesity in EP3^(−/−)and EP3β***,both EP3^(−/−)and EP3βmice had increased lipolysis in WAT mainly due to the activated cAMP/PKA/hormone-sensitive lipase *** together,our findings suggest that EP3 receptor and itsαandγisoforms are involved in both adipogenesis and lipolysis and influence food intake,serum lipid levels,and insulin sensitivity.

关键词： arachidonic acid EP3 receptor isoform PKA PPARγ insulin resistance obesity

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Perivascular localized cells commit erythropoiesis in PDGF-B-expressing solid tumors

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Cancer Communications 2023年第6期43卷 637-660页

作者： Kayoko Hosaka Chenchen Wang Shiyue Zhang Xue Lv Takahiro Seki Yin Zhang Xu Jing Jieyu Wu Qiqiao Du Xingkang He Yulong Fan Xuan Li Makoto Kondo Masahito Yoshihara Hong Qian Lihong Shi Ping Zhu Yuanfu Xu Yunlong Yang Tao Cheng Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholmSweden State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinP.R.China Tianjin Institutes of Health Science TianjinP.R.China School of Pharmacology Binzhou Medical UniversityYantaiShandongP.R.China Department of Clinical Laboratory the Second Hospital of Shandong UniversityJinanShandongP.R.China Department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University Medical SchoolHangzhouZhejiangP.R.China center for Hematology and Regenerative Medicine Department of MedicineKarolinska InstituteKarolinska University HospitalStockholmSweden Department of Biosciences and Nutrition Karolinska InstituteHuddingeSweden Department of Cellular and Genetic Medicine School of Basic Medical SciencesFudan UniversityShanghaiP.R.China

Background:Tumors possess incessant growth features,and expansion of their masses demands sufficient oxygen supply by red blood cells(RBCs).In adult mammals,the bone marrow(BM)is the main organ regulating hematopoiesis with dedicated *** than BM,extramedullary hematopoiesis is discovered in various pathophysiological ***,whether tumors can contribute to hematopoiesis is completely *** evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other ***,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate ***:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived *** tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in ***-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological *** production of erythroid differentiationspecific cytokine,erythropoietin(EPO),in TME was checked using quantitative polymerase chain reaction(qPCR),enzyme-linked immunosorbent assay(ELISA,magnetic-activated cell sorting and *** investigate BM function in tumor erythropoiesis,BM transplantation mouse models were ***:Genome-wide expression profiling showed that in response to plateletderived growth factor subunit B(PDGF-B),neural/glial antigen 2(NG2)+perivascular localized cells exhibited hematopoietic stem and progenitor-like features and underwent differentiation towards the erythroid ***-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates *** analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived sub

关键词： cancer hematopoiesis PDGF-B perivascular localized cell stem cell tumor vasculature

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Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic steatohepatitis?

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World Journal of Gastroenterology 2016年第31期22卷 6965-6971页

作者： Priya Handa Akhila Vemulakonda Kris V Kowdley Misael Uribe Nahum Méndez-Sánchez Senior Research Scientist Organ Care Research and Liver Care Network Swedish Medical Center Liver Research Unit Medica Sur Clinic and Foundation

Nonalcoholic fatty liver disease(NAFLD) is the most common liver disease worldwide, affecting approximately one third of the Western world. It consists of a wide spectrum of liver disorders, ranging from fatty liver to nonalcoholic steatohepatitis(NASH), which consists of steatosis, ballooning injury and inflammation. Despite an alarming growth in the statistics surrounding NAFLD, there are as yet no effective therapies for its treatment. Innate immune signaling has been thought to play a significant role in initiating and augmenting hepatic inflammation, contributing to the transition from nonalcoholic fatty liver to NASH. An immune response is triggered by countless signals called damage-associated molecular patterns(DAMPs) elicited by lipid-laden and damaged hepatocytes, which are recognized by pattern recognition receptors(PRRs) on hepatic immune cells to initiate inflammatory signaling. In this editorial, in addition to summarizing innate immune signaling in NAFLD and discussing potential therapies that target innate immune pathways, we have described a recent study that demonstrated that mitochondrial DNA serves as a DAMP activating a hepatic PRR, TLR9, in mice and in the plasma of NASH patients. In addition to identifying a new ligand for TLR9 during NASH progression, the study shows that blocking TLR9 reverses NASH, paving the way for the development of future NASH therapy.

关键词： TLR9 Damage-associated molecular patterns Products of microbial metabolism produced by pathogens Mitochondrial DNA Hepatocytes Nonalcoholic steatohepatitis Nonalcoholic fatty liver disease Inflammation Innate immune signaling Kupffer cells Therapy

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A highly selective C-rhamnosyltransferase from Viola tricolor and insights into its mechanisms

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3535-3544页

作者： Bo-Yun Han Zi-Long Wang Junhao Li Qing Jin Hao-Tian Wang Kuan Chen Yang Yi Hansgren Xue Qiao Min Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Physics and Astronomy Uppsala UniversityUppsala SE-75120Sweden College of Life Science Anhui Agricultural UniversityHefei 230036China Peking University-Yunnan Baiyao International medical Research center Beijing 100191China

C-Glycosides are important natural products with various *** plant biosynthetic pathways,the C-glycosylation step is usually catalyzed by C-glycosyltransferases(CGTs),and most of them prefer to accept uridine 5’-diphosphate glucose(UDP-Glc)as sugar *** CGTs favoring UDP-rhamnose(UDP-Rha)as sugar donor has been reported,thus ***,we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola *** could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside,and exhibited high selectivity towards *** for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics(MD)simulations and molecular mechanics with generalized Born and surface area solvation(MM/GBSA)binding free energy ***144 played a vital role in recognizing UDP-Rha,and the V144T mutant could efficiently utilize *** work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

关键词： Flavonoid C-glycoside C-rhamnosyltransferase Biosynthesis Catalytic mechanisms Sugardonorselectivity

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A Case Report: Prolonged Psychosis Secondary to Use of Highly Concentrated Tetra Hydro Cannabinoid (THC) (DABS)

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Open Journal of Psychiatry 2022年第1期12卷 49-52页

作者： Srinivas Dannaram Madhuri Pulluri Christina Regan Banner Thunderbird medical center Department of Psychiatry College of Medicine-Phoenix University of Arizona Glendale Arizona USA

The Association of Schizophrenia, psychosis, and Marijuana is decades old. swedish Conscripts cohort study [1] was one of the earlier studies which reported dose-dependent associations between Marijuana use and schizophrenia. This landmark study was substantiated in other countries through research and systematic reviews [2], which further strengthened the dose-dependent association between Marijuana and Psychosis. The dose defined in these studies [1] was based on the frequency of use that is more times used means more risk of developing schizophrenia and or related psychosis. The concept of using highly concentrated marijuana is relatively new, especially in the light of episodes lasting longer than anticipated with treatment resistance. There is not much data on how it will change the course of psychosis and affect the current diagnostic criteria for Substance-induced psychosis, Schizophreniform Psychosis, and schizophrenia. Based on these challenges, we report a case of Dabs or concentrated Tetra Hydro Cannabinoid (THC)-induced prolonged psychosis with tachycardia and treatment resistance on two separate occasions. Both inpatient admissions were triggered using concentrated Tetra Hydro Cannabinoid (THC).

关键词： Schizophrenia Psychosis Marijuana THC

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Import Determinants of Organelle-Specific and Dual Targeting Peptides of Mitochondria and Chloroplasts in Arabidopsis thaliana

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Molecular Plant 2014年第1期7卷 121-136页

作者： Changrong Ge Erika Spanning Elzbieta Glaser Ake Wieslander Department of Biochemistry and Biophysics Center for Biomembrane Research Stockholm University SE-106 91 Stockholm Sweden medical Inflammation Research Department of Medical Biochemistry and Biophysics Karolinska Institute SE-171 77 Stockholm Sweden

Most of the mitochondrial and chloroplastic proteins are synthesized in the cytosol as precursor proteins carrying an N-terminal targeting peptide （TP） directing them specifically to a correct organelle. However, there is a group of proteins that are dually targeted to mitochondria and chloroplasts using an ambiguous N-terminal dual targeting peptide （dTP）. Here, we have investigated pattern properties of import determinants of organelle-specific TPs and dTPs combining mathematical multivariate data analysis （MVDA） with in vitro organellar import studies. We have used large datasets of mitochondrial and chloroplastic proteins found in organellar proteomes as well as manually selected data sets of experimentally confirmed organelle-specific TPs and dTPs from Arabidopsis thaliana. Two classes of organelle-specific TPs could be distinguished by MVDA and potential patterns or periodicity in the amino acid sequence contributing to the separation were revealed, dTPs were found to have intermediate sequence features between the organelle-specific TPs. Interestingly, introducing positively charged residues to the dTPs showed clustering towards the mitochondrial TPs in silico and resulted in inhibition of chloroplast, but not mitochondrial import in in vitro organellar import studies. These findings suggest that positive charges in the N-terminal region of TPs may function as an ＇avoidance signal＇ for the chloroplast import.

关键词： dual targeting ambiguous targeting signal mitochondria chloroplast protein import partial least square discriminant analysis Arabidopsis thaliana.

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Characterization of patients with both alcoholic and nonalcoholic fatty liver disease in a large United States cohort

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World Journal of Hepatology 2019年第10期11卷 710-718页

作者： George Khoudari Amandeep Singh Mazen Noureddin Danielle Fritze Rocio Lopez Imad Asaad Eric Lawitz Fred Poordad Kris V Kowdley Naim Alkhouri Department of Hospital Medicine Cleveland Clinic FoundationClevelandOH 44195United States Department of Gastroenterology and Hepatology Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology and Hepatology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of General Surgery Texas Liver Institute and University of Texas HealthSan AntonioTX 78215United States Department of Quantitative Health Sciences Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology Metro Health SystemClevelandOH 44109United States Texas Liver Institute and University of Texas Health San AntonioTX 78215United States swedish Liver Care Network Swedish Medical CenterSeattleWA 98122United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the hepatic manifestation of the metabolic syndrome(MetS)and is characterized by steatosis in the absence of significant alcohol ***,MetS and significant alcohol intake coexist in certain individuals which may lead to the development of *** To assess the clinical characteristics of patients with both alcoholic and NAFLD(BAFLD)in a large cohort in the United *** Adults from the National Health and Nutrition Examination Survey between 2003-2014 were *** was diagnosed based on elevated alanine aminotransferase(ALT)and being overweight or obese in the absence of other liver *** patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessive amounts of *** and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score(FIB4 index).RESULTS The prevalence of NAFLD was at 25.9%(95%CI;25.1-26.8)and that of BAFLD was 0.84%(0.67,1.02)which corresponds to an estimated 1.24 million Americans affected by *** to NAFLD,patients with BAFLD were more likely to be male,smokers,have higher ALT,aspartate aminotransferase,triglycerides,and lower platelets;P2.67 was 3.2(1.4,7.0),P=0.004].CONCLUSION A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.

关键词： Non-alcoholic fatty liver disease Alcoholic liver disease Fatty liver disease

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Regional GIS-based evaluation of the potential and supply costs of forest biomass in Sweden

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Frontiers of Agricultural Science and Engineering 2017年第4期4卷 493-501页

作者： Dimitris ATHANASSIADIS Tomas NORDFJELL Department of Forest Biomaterials and Technology Swedish University of Agricultural SciencesSE-90183 UmeåSweden

The potential for harvestable forest fuel(logging residues and stumps from regeneration fellings and small diameter trees from early thinnings) in Sweden,divided in five regions, is provided. Marginal cost curves for logging residues and stumps are calculated through a GIS-based method based on forest inventory plots and locations of selected terminals, and heat and combined heat and power facilities. Four supply chains for logging residues and two for stumpwood were compared. Fixed and variable costs of harvesting equipment and transport vehicles were used for determining the costs of each of the supply systems under consideration. A list with the GPS coordinates of all facilities and terminals was made based on their geographical location. The distance from the center of each forest inventory plot to the nearest receiving point within the region, either facility or terminal, was estimated. There were large differences in the estimated potential of harvestable forest fuel between the *** overall annual potential for each of the five regions ranged from 0.97 to 2.73 million oven dry tonnes and the total potential amounted to 9.39 Mt(oven dry). One of the northernmost regions(R1) had the steepest slope in its marginal cost curve. For the other regions, the slope of their cost curves was less dramatic. Information on the economic availability of logging residues and stumps in each region is important for forest fuel suppliers and receiving facilities.

关键词： GIS logging residues heat and-power facilities stumpwood

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Identification of Lignin and Polysaccharide Modifications in Populus Wood by Chemometric Analysis of 2D NMR Spectra from Dissolved Cell Walls

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Molecular Plant 2009年第5期2卷 933-942页

作者： Mattias Hedenstrom Susanne Wiklund-Lindstrom Tommy Oman Fachuang Lu Lorenz Gerber Paul Schatz Bjorn Sundberg John Ralph Department of Chemistry Umea University SE-90187 Umea Sweden Department of Biochemistry and Great Lakes Bioenergy Research Center University of Wisconsin Madison WI 53706 USA Umea Plant Science Centre Department of Forest Genetics and Plant Physiology Swedish University of Agricultural Sciences SE-90183 Umea Sweden US Dairy Forage Research center USDA-Agricultural Research Service Madison WI 53706 USA

2D ^13C-^1H HSQC NMR spectroscopy of acetylated cell walls in solution gives a detailed fingerprint that can be used to assess the chemical composition of the complete wall without extensive degradation. We demonstrate how multivariate analysis of such spectra can be used to visualize cell wall changes between sample types as high-resolution 2D NMR loading spectra. Changes in composition and structure for both lignin and polysaccharides can subsequently be interpreted on a molecular level. The multivariate approach alleviates problems associated with peak picking of overlapping peaks, and it allows the deduction of the relative importance of each peak for sample discrimination. As a first proof of concept, we compare Populus tension wood to normal wood. All well established differences in cellulose, hemicellulose, and lignin compositions between these wood types were readily detected, confirming the reliability of the multivariate approach, In a second example, wood from transgenic Populus modified in their degree of pectin methylesterification was compared to that of wild-type trees. We show that differences in both lignin and polysaccharide composition that are difficult to detect with traditional spectral analysis and that could not be a priori predicted were revealed by the multivariate approach. 2D NMR of dissolved cell wall samples combined with multivariate analysis constitutes a novel approach in cell wall analysis and provides a new tool that will benefit cell wall research.

关键词： Aspen biostatistics cell walls multivariate data analysis NMR spectroscopy tension wood

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Endocrine impact of Helicobacter pylori:Focus on ghrelin and ghrelin o-acyltransferase

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World Journal of Gastroenterology 2011年第10期17卷 1249-1260页

作者： Penny L Jeffery Michael A McGuckin Sara K Linden Mucosal Diseases Program Mater Medical Research InstituteMater Health Services Mucosal Immunobiology and Vaccine center Sahlgrenska AcademyUniversity of Gothenburg

Ghrelin is predominantly produced by the gastric enteroendocrine cell compartment and is octanoylated by the recently discovered ghrelin o-acyltransferase (GOAT) before secretion into the bloodstream. This octanoylation is essential for many of the biological properties of ghrelin including appetite stimulation and anti-inflammatory properties as only the acylated form of ghrelin binds to the ghrelin receptor, the growth hormone secretagogue receptor (GHS-R). Given the gastric location of ghrelin production, it is perhaps not surprising that insult to the gastric mucosa affects circulating ghrelin levels in humans. Helicobacter pylori (H. pylori) infects more than f ifty percent of the world's population and once established within the gastric mucosa, can persist for life. Infection is associated with chronic gastritis, gastric atrophy and ulceration, reduced appetite and a lower body mass index (BMI). The large majority of studies investigating levels of circulating ghrelin and ghrelin expression in the stomach in patients with H. pylori infection indicate that the bacterium has a negative impact on ghrelin production and/or secretion. Eradication of infection restores ghrelin, improves appetite and increases BMI in some studies, however, a causative relationship between H. pylori-associated serum ghrelin decline and food intake and obesity has not been established. Most studies measure total ghrelin in the circulation although the measurement of the ratio of acyl/total ghrelin gives a clearer indication that the ghrelin acylation process is altered during infection and atrophy. GOAT is essential for the production of biologically-active, acyl ghrelin and the impact of H. pylori on GOAT expression and activity will be highly informative in the future.

关键词：酰基转移酶内分泌细胞生长素 ghrelin 幽门螺杆菌 Ghrelin 山羊生产生物学特性

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