PPAR Research最新文献

{"title":"Erratum to \"Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy\".","authors":"Kay-Dietrich Wagner,&nbsp;Ana Vukolic,&nbsp;Delphine Baudouy,&nbsp;Jean-François Michiels,&nbsp;Nicole Wagner","doi":"10.1155/2018/5480829","DOIUrl":"https://doi.org/10.1155/2018/5480829","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2016/7631085.].</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"5480829"},"PeriodicalIF":2.9,"publicationDate":"2018-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/5480829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36748576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signaling Mechanisms of Selective PPAR<i>γ</i> Modulators in Alzheimer's Disease.","authors":"Manoj Govindarajulu, Priyanka D Pinky, Jenna Bloemer, Nila Ghanei, Vishnu Suppiramaniam, Rajesh Amin","doi":"10.1155/2018/2010675","DOIUrl":"10.1155/2018/2010675","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. The continuous increase in the incidence of AD with the aged population and mortality rate indicates the urgent need for establishing novel molecular targets for therapeutic potential. Peroxisome proliferator-activated receptor gamma (PPAR<i>γ</i>) agonists such as rosiglitazone and pioglitazone reduce amyloid and tau pathologies, inhibit neuroinflammation, and improve memory impairments in several rodent models and in humans with mild-to-moderate AD. However, these agonists display poor blood brain barrier permeability resulting in inadequate bioavailability in the brain and thus requiring high dosing with chronic time frames. Furthermore, these dosing levels are associated with several adverse effects including increased incidence of weight gain, liver abnormalities, and heart failure. Therefore, there is a need for identifying novel compounds which target PPAR<i>γ</i> more selectively in the brain and could provide therapeutic benefits without a high incidence of adverse effects. This review focuses on how PPAR<i>γ</i> agonists influence various pathologies in AD with emphasis on development of novel selective PPAR<i>γ</i> modulators.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"2010675"},"PeriodicalIF":3.5,"publicationDate":"2018-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36658916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Pioglitazone on Nonalcoholic Fatty Liver Disease in the Absence of Constitutive Androstane Receptor Expression.","authors":"Hwa Young Ahn,&nbsp;Hwan Hee Kim,&nbsp;Ji-Yeon Hwang,&nbsp;Changhun Park,&nbsp;Bo Youn Cho,&nbsp;Young Joo Park","doi":"10.1155/2018/9568269","DOIUrl":"https://doi.org/10.1155/2018/9568269","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease or steatohepatitis (NAFLD/NASH) is a fatty liver disease that is closely related to obesity, diabetes, and dyslipidemia. Pioglitazone, which was developed as an antidiabetic drug, is known to improve NALFD. Pioglitazone is metabolized by multiple cytochrome P450 (CYP) enzymes, which are regulated by the xenobiotic receptor constitutive androstane receptor (CAR). In this study, we investigated the effects of pioglitazone on NAFLD by absence of CAR activity under high-fat (HF)-fed conditions. CAR^-/- mice showed significant improvement in NALFD after 12 weeks of pioglitazone treatment compared to wild-type mice. This improvement in NAFLD persisted in CAR^-/- mice regardless of blood pioglitazone concentration. The expression of lipogenesis genes in the liver, sterol-regulatory element binding protein-1c (SREBP-1c), and stearoyl-CoA desaturase (SCD)-1 was decreased after pioglitazone treatment in HF-fed CAR^-/- mice. In addition, the expression of peroxisome proliferator-activated receptor gamma 2 (PPAR<i>γ</i>2) was decreased by pioglitazone in HF-fed CAR^-/- mice. Changes in SREBP-1c and PPAR <i>γ</i>2 remained constant over short-term (6 h) pioglitazone and lipid injection. Our results showed that NAFLD was improved significantly by pioglitazone in a CAR deletion state. These results might be valuable because they suggest that interaction with CAR and pioglitazone/PPAR<i>γ</i>2 may be important in regulating gene expression associated with NAFLD.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"9568269"},"PeriodicalIF":2.9,"publicationDate":"2018-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/9568269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36620635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Reduction in ADAM17 Expression Is Involved in the Protective Effect of the PPAR-<i>α</i> Activator Fenofibrate on Pressure Overload-Induced Cardiac Hypertrophy.","authors":"Si-Yu Zeng,&nbsp;Hui-Qin Lu,&nbsp;Qiu-Jiang Yan,&nbsp;Jian Zou","doi":"10.1155/2018/7916953","DOIUrl":"https://doi.org/10.1155/2018/7916953","url":null,"abstract":"<p><p>The peroxisome proliferator-activated receptor-<i>α</i> (PPAR-<i>α</i>) agonist fenofibrate ameliorates cardiac hypertrophy; however, its mechanism of action has not been completely determined. Our previous study indicated that a disintegrin and metalloproteinase-17 (ADAM17) is required for angiotensin II-induced cardiac hypertrophy. This study aimed to determine whether ADAM17 is involved in the protective action of fenofibrate against cardiac hypertrophy. Abdominal artery constriction- (AAC-) induced hypertensive rats were used to observe the effects of fenofibrate on cardiac hypertrophy and ADAM17 expression. Primary cardiomyocytes were pretreated with fenofibrate (10 <i>μ</i>M) for 1 hour before being stimulated with angiotensin II (100 nM) for another 24 hours. Fenofibrate reduced the ratios of left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW), left ventricular anterior wall thickness (LVAW), left ventricular posterior wall thickness (LVPW), and ADAM17 mRNA and protein levels in left ventricle in AAC-induced hypertensive rats. Similarly, <i>in vitro</i> experiments showed that fenofibrate significantly attenuated angiotensin II-induced cardiac hypertrophy and diminished ADAM17 mRNA and protein levels in primary cardiomyocytes stimulated with angiotensin II. In summary, a reduction in ADAM17 expression is associated with the protective action of PPAR-<i>α</i> agonists against pressure overload-induced cardiac hypertrophy.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"7916953"},"PeriodicalIF":2.9,"publicationDate":"2018-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/7916953","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36394929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Rosiglitazone and Forskolin Have Neuroprotective Effects in SD Rats after Spinal Cord Injury.","authors":"Qing-Qi Meng,&nbsp;Wei Lei,&nbsp;Hao Chen,&nbsp;Zhen-Cheng Feng,&nbsp;Li-Qiong Hu,&nbsp;Xing-Liang Zhang,&nbsp;Siming Li","doi":"10.1155/2018/3897478","DOIUrl":"https://doi.org/10.1155/2018/3897478","url":null,"abstract":"<p><p>The peroxisome proliferator-activated receptor gamma (PPAR-<i>γ</i>) agonist rosiglitazone inhibits NF-<i>κ</i>B expression and endogenous neural stem cell differentiation into neurons and reduces the inflammatory cascade after spinal cord injury (SCI). The aim of this study was to explore the mechanisms underlying rosiglitazone-mediated neuroprotective effects and regulation of the balance between the inflammatory cascade and generation of endogenous spinal cord neurons by using a spinal cord-derived neural stem cell culture system as well as SD rat SCI model. Activation of PPAR-<i>γ</i> could promote neural stem cell proliferation and inhibit PKA expression and neuronal formation <i>in vitro.</i> In the SD rat SCI model, the rosiglitazone + forskolin group showed better locomotor recovery compared to the rosiglitazone and forskolin groups. MAP2 expression was higher in the rosiglitazone + forskolin group than in the rosiglitazone group, NF-<i>κ</i>B expression was lower in the rosiglitazone + forskolin group than in the forskolin group, and NeuN expression was higher in the rosiglitazone + forskolin group than in the forskolin group. PPAR-<i>γ</i> activation likely inhibits NF-<i>κ</i>B, thereby reducing the inflammatory cascade, and PKA activation likely promotes neuronal cell regeneration.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"3897478"},"PeriodicalIF":2.9,"publicationDate":"2018-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/3897478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36335822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with Lobeglitazone Attenuates Hepatic Steatosis in Diet-Induced Obese Mice.","authors":"Sorim Choung,&nbsp;Kyong Hye Joung,&nbsp;Bo Ram You,&nbsp;Sang Ki Park,&nbsp;Hyun Jin Kim,&nbsp;Bon Jeong Ku","doi":"10.1155/2018/4292509","DOIUrl":"https://doi.org/10.1155/2018/4292509","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism. Lobeglitazone treatment for 4 weeks in high fat diet- (HFD-) induced obese mice (HL group) improved insulin resistance and glucose intolerance compared to HFD-induced obese mice (HU group). The gene levels related to hepatic gluconeogenesis also decreased after treatment by lobeglitazone. The livers of mice in the HL group showed histologically reduced lipid accumulation, with lowered total plasma cholesterol and triglyceride levels. In addition, the HL group significantly decreased the hepatic expression of genes associated with lipid synthesis, cholesterol biosynthesis, and lipid droplet development and increased the hepatic expression of genes associated with fatty acid <i>β</i>-oxidation, thus suggesting that lobeglitazone decreased hepatic steatosis and reversed hepatic lipid dysregulation. Livers with steatohepatitis contained increased levels of PPAR<i>γ</i> and phosphorylated PPAR<i>γ</i> at serine 273, leading to downregulation of expression of genes associated with insulin sensitivity. Notably, the treatment of lobeglitazone increased the protein levels of PPAR<i>α</i> and diminished levels of PPAR<i>γ</i> phosphorylated at serine 273, which were increased by a HFD, suggesting that induction of PPAR<i>α</i> and posttranslational modification of PPAR<i>γ</i> in livers by lobeglitazone might be an underlying mechanism of the improvement seen in NAFLD. Taken together, our data showed that lobeglitazone might be an effective treatment for NAFLD.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"4292509"},"PeriodicalIF":2.9,"publicationDate":"2018-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/4292509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36313469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of GPR43 in Brown Adipogenesis Is Enhanced by Rosiglitazone and Controlled by PPAR<i>γ</i>/RXR Heterodimerization.","authors":"Jiamiao Hu,&nbsp;Arong Zhou,&nbsp;Peter C K Cheung,&nbsp;Baodong Zheng,&nbsp;Shaoxiao Zeng,&nbsp;Shaoling Lin","doi":"10.1155/2018/1051074","DOIUrl":"https://doi.org/10.1155/2018/1051074","url":null,"abstract":"<p><p>GPR43, a G-protein coupled receptor recognizing short-chain fatty acids, has been reported to participate in many biological functions of white adipocytes, such as adipogenesis and lipolysis. However, the functional role of GPR43 in brown adipocytes is still not clear. In this study, we investigated the effects of the PPAR<i>γ</i> agonist rosiglitazone on GPR43 expression in brown adipogenesis. The results demonstrated that GPR43 was expressed during the late phase of brown adipocyte differentiation, which could be further augmented by adipogenic agent rosiglitazone treatment. The PPAR<i>γ</i>/RXR heterodimerization was found to be the key transcription factor for this enhancing effect of rosiglitazone on GPR43 expression. Taken together, these results suggested GPR43 levels might be regulated by PPAR<i>γ</i>-activated events during brown adipocytes differentiation and reflect the adipogenesis status of brown adipocytes.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"1051074"},"PeriodicalIF":2.9,"publicationDate":"2018-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/1051074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36188554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Effects of a Novel PPAR-<i>γ</i> Agonist MEKT1 on <i>Pomc</i> Expression/ACTH Secretion in AtT20 Cells.","authors":"Rehana Parvin,&nbsp;Erika Noro,&nbsp;Akiko Saito-Hakoda,&nbsp;Hiroki Shimada,&nbsp;Susumu Suzuki,&nbsp;Kyoko Shimizu,&nbsp;Hiroyuki Miyachi,&nbsp;Atsushi Yokoyama,&nbsp;Akira Sugawara","doi":"10.1155/2018/5346272","DOIUrl":"https://doi.org/10.1155/2018/5346272","url":null,"abstract":"<p><p>Although therapeutic effects of the peroxisome proliferator-activated receptor gamma (PPAR-<i>γ</i>) agonists rosiglitazone and pioglitazone against Cushing's disease have been reported, their effects are still controversial and inconsistent. We therefore examined the effects of a novel PPAR-<i>γ</i> agonist, MEKT1, on <i>Pomc</i> expression/ACTH secretion using murine corticotroph-derived AtT20 cells and compared its effects with those of rosiglitazone and pioglitazone. AtT20 cells were treated with either 1 nM~10 <i>μ</i>M MEKT1, rosiglitazone, or pioglitazone for 24 hours. Thereafter, their effects on proopiomelanocortin gene <i>(Pomc)</i> mRNA expression were studied by qPCR and the <i>Pomc</i> promoter (-703/+58) activity was demonstrated by luciferase assay. <i>Pomc</i> mRNA expression and promoter activity were significantly inhibited by MEKT1 at 10 <i>μ</i>M compared to rosiglitazone and pioglitazone. SiRNA-mediated PPAR-<i>γ</i> knockdown significantly abrogated MEKT1-mediated <i>Pomc</i> mRNA suppression. ACTH secretion from AtT20 cells was also significantly inhibited by MEKT1. Deletion/point mutant analyses of <i>Pomc</i> promoter indicated that the MEKT1-mediated suppression was mediated via NurRE, TpitRE, and NBRE at -404/-383, -316/-309, and -69/-63, respectively. Moreover, MEKT1 significantly suppressed <i>Nur77</i>, <i>Nurr1</i>, and <i>Tpit</i> mRNA expression. MEKT1 also was demonstrated to inhibit the protein-DNA interaction of Nur77/Nurr1-NurRE, Tpit-TpitRE, and Nur77-NBRE by ChIP assay. Taken together, it is suggested that MEKT1 could be a novel therapeutic medication for Cushing's disease.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"5346272"},"PeriodicalIF":2.9,"publicationDate":"2018-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/5346272","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36177717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular and Biophysical Pipeline for the Screening of Peroxisome Proliferator-Activated Receptor Beta/Delta Agonists: Avoiding False Positives.","authors":"Natália Bernardi Videira,&nbsp;Fernanda Aparecida Heleno Batista,&nbsp;Artur Torres Cordeiro,&nbsp;Ana Carolina Migliorini Figueira","doi":"10.1155/2018/3681590","DOIUrl":"https://doi.org/10.1155/2018/3681590","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptor beta/delta (PPARß/<i>δ</i>) is considered a therapeutic target for metabolic disorders, cancer, and cardiovascular diseases. Here, we developed one pipeline for the screening of PPARß/<i>δ</i> agonists, which reduces the cost, time, and false-positive hits. The first step is an optimized 3-day long cellular transactivation assay based on reporter-gene technology, which is supported by automated liquid-handlers. This primary screening is followed by a confirmatory transactivation assay and by two biophysical validation methods (thermal shift assay (TSA) and (ANS) fluorescence quenching), which allow the calculation of the affinity constant, giving more information about the selected hits. All of the assays were validated using well-known commercial agonists providing trustworthy data. Furthermore, to validate and test this pipeline, we screened a natural extract library (560 extracts), and we found one plant extract that might be interesting for PPARß/<i>δ</i> modulation. In conclusion, our results suggested that we developed a cheaper and more robust pipeline that goes beyond the single activation screening, as it also evaluates PPARß/<i>δ</i> tertiary structure stabilization and the ligand affinity constant, selecting only molecules that directly bind to the receptor. Moreover, this approach might improve the effectiveness of the screening for agonists that target PPARß/<i>δ</i> for drug development.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"3681590"},"PeriodicalIF":2.9,"publicationDate":"2018-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/3681590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36177715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Hepatoprotection by Oleanolic Acid Preconditioning: Focusing on PPAR<i>α</i> Activation.","authors":"Wenwen Wang,&nbsp;Kan Chen,&nbsp;Yujing Xia,&nbsp;Wenhui Mo,&nbsp;Fan Wang,&nbsp;Weiqi Dai,&nbsp;Peiqin Niu","doi":"10.1155/2018/3180396","DOIUrl":"https://doi.org/10.1155/2018/3180396","url":null,"abstract":"<p><strong>Objective: </strong>Previous studies have characterized the hepatoprotective and anti-inflammatory properties of oleanolic acid (OA). This study aimed to investigate the molecular mechanisms of OA hepatoprotection in concanavalin A- (ConA-) induced acute liver injury.</p><p><strong>Materials and methods: </strong>ConA (20 mg/kg) was intravenously injected to induce acute liver injury in Balb/C mice. OA pretreatment (20, 40, and 80 mg/kg) was administered subcutaneously once daily for 3 consecutive days prior to treatment with ConA; 2, 8, and 24 h after ConA injection, the levels of serum liver enzymes and the histopathology of major factors and inflammatory cytokines were determined.</p><p><strong>Results: </strong>OA reduced the release of serum liver enzymes and inflammatory factors and prevented ConA mediated damage to the liver. OA elevated the expression levels of peroxisome proliferator-activated receptor alpha (PPAR<i>α</i>) and decreased the phosphorylation of c-Jun NH2-terminal kinase (JNK).</p><p><strong>Conclusion: </strong>OA exhibits anti-inflammatory properties during ConA-induced acute liver injury by attenuating apoptosis and autophagy through activation of PPAR<i>α</i> and downregulation of JNK signaling.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2018 ","pages":"3180396"},"PeriodicalIF":2.9,"publicationDate":"2018-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/3180396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36135322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}