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Clinical significance of serum omentin-1 levels in patients with pancreatic adenocarcinoma 胰腺腺癌患者血清网膜蛋白-1水平的临床意义
BBA clinical Pub Date : 2016-12-01 DOI: 10.1016/j.bbacli.2016.10.002
Senem Karabulut , Cigdem Usul Afsar , Mehmet Karabulut , Halil Alis , Mehmet Abdussamet Bozkurt , Fatma Aydogan , Murat Serilmez , Faruk Tas
{"title":"Clinical significance of serum omentin-1 levels in patients with pancreatic adenocarcinoma","authors":"Senem Karabulut ,&nbsp;Cigdem Usul Afsar ,&nbsp;Mehmet Karabulut ,&nbsp;Halil Alis ,&nbsp;Mehmet Abdussamet Bozkurt ,&nbsp;Fatma Aydogan ,&nbsp;Murat Serilmez ,&nbsp;Faruk Tas","doi":"10.1016/j.bbacli.2016.10.002","DOIUrl":"10.1016/j.bbacli.2016.10.002","url":null,"abstract":"<div><h3>Background</h3><p>Omentin is related with metabolic syndrome and obesity. Pancreatic adenocarcinoma (PA) is a lethal and obesity-linked malignancy. This study was conducted to investigate the serum levels of omentin in patients with PA and the relationship with tumor progression and known prognostic parameters.</p></div><div><h3>Material and methods</h3><p>Serum samples were obtained from thirty-three patients on first admission before any treatment. Age, sex and body mass index (BMI) matched 30 healthy controls were included in the analysis. Both serum omentin levels were measured using enzyme-linked immunosorbent assay (ELISA).</p></div><div><h3>Results</h3><p>The median age at diagnosis was 59<!--> <!-->years (32–84<!--> <!-->years). Twenty (61%) patients were men and the remaining were women. The most common metastatic site was liver in 23 patients with metastasis (n<!--> <!-->=<!--> <!-->19, 83%). Thirty-nine percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx–responsive. Median overall survival of the whole group was 41.3<!--> <!-->±<!--> <!-->8.3<!--> <!-->weeks [95% confidence interval (CI)<!--> <!-->=<!--> <!-->25–58<!--> <!-->weeks]. The baseline serum omentin levels were significantly higher in patients with PA than in the control group (p<!--> <!-->&lt;<!--> <!-->0.001). Serum omentin levels were significantly higher in patients with larger pathologic tumor size compared with smaller size (p<!--> <!-->=<!--> <!-->0.03). Conversely, serum omentin concentration was found to have no prognostic role on survival (p<!--> <!-->=<!--> <!-->0.54).</p></div><div><h3>Conclusion</h3><p>Serum levels of omentin may have a good diagnostic role in patients with PA.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.10.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Controversies and evidence of hepatic resection for hepatocellular carcinoma 肝细胞癌肝切除术的争议与证据
BBA clinical Pub Date : 2016-12-01 DOI: 10.1016/j.bbacli.2016.10.001
Jian-Hong Zhong , Guido Torzilli , Hao Xing , Chao Li , Jun Han , Lei Liang , Han Zhang , Shu-Yang Dai , Le-Qun Li , Feng Shen , Tian Yang
{"title":"Controversies and evidence of hepatic resection for hepatocellular carcinoma","authors":"Jian-Hong Zhong ,&nbsp;Guido Torzilli ,&nbsp;Hao Xing ,&nbsp;Chao Li ,&nbsp;Jun Han ,&nbsp;Lei Liang ,&nbsp;Han Zhang ,&nbsp;Shu-Yang Dai ,&nbsp;Le-Qun Li ,&nbsp;Feng Shen ,&nbsp;Tian Yang","doi":"10.1016/j.bbacli.2016.10.001","DOIUrl":"10.1016/j.bbacli.2016.10.001","url":null,"abstract":"<div><p>Symptoms of early hepatocellular carcinoma (HCC) often go unnoticed, so more than half of patients with primary HCC are diagnosed after their disease has already reached an intermediate or advanced stage, or after portal hypertension has appeared. While hepatic resection is widely recognized as a first-line therapy to treat very early or early HCC, its use in treating intermediate or advanced HCC or HCC involving portal hypertension remains controversial. Here we review PubMed-indexed literature covering the use of hepatic resection for such patients. The available evidence strongly suggests that, as a result of improvements in surgical techniques and perioperative care, hepatic resection can benefit many patients with intermediate or advanced HCC or with HCC associated with portal hypertension.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.10.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Metabolic response to glatiramer acetate therapy in multiple sclerosis patients 多发性硬化症患者醋酸格拉替默治疗的代谢反应
BBA clinical Pub Date : 2016-12-01 DOI: 10.1016/j.bbacli.2016.10.004
Lidia De Riccardis , Alessandra Ferramosca , Antonio Danieli , Giorgio Trianni , Vincenzo Zara , Francesca De Robertis , Michele Maffia
{"title":"Metabolic response to glatiramer acetate therapy in multiple sclerosis patients","authors":"Lidia De Riccardis ,&nbsp;Alessandra Ferramosca ,&nbsp;Antonio Danieli ,&nbsp;Giorgio Trianni ,&nbsp;Vincenzo Zara ,&nbsp;Francesca De Robertis ,&nbsp;Michele Maffia","doi":"10.1016/j.bbacli.2016.10.004","DOIUrl":"10.1016/j.bbacli.2016.10.004","url":null,"abstract":"<div><p>Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4<sup>+</sup>, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4<sup>+</sup> T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6<!--> <!-->months during the 12<!--> <!-->months of GA administration. GA treated patients' CD4<sup>+</sup> T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4<sup>+</sup> T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.10.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54182122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Lymph node or perineural invasion is associated with low miR-15a, miR-34c and miR-199b levels in head and neck squamous cell carcinoma 在头颈部鳞状细胞癌中,淋巴结或神经周围浸润与miR-15a、miR-34c和miR-199b低水平相关
BBA clinical Pub Date : 2016-12-01 DOI: 10.1016/j.bbacli.2016.11.001
Lucas O. Sousa , Lays M. Sobral , Camila S. Matsumoto , Fabiano P. Saggioro , Rossana V.M. López , Rodrigo A. Panepucci , Carlos Curti , Wilson A. Silva Jr , Lewis J. Greene , Andréia M. Leopoldino
{"title":"Lymph node or perineural invasion is associated with low miR-15a, miR-34c and miR-199b levels in head and neck squamous cell carcinoma","authors":"Lucas O. Sousa ,&nbsp;Lays M. Sobral ,&nbsp;Camila S. Matsumoto ,&nbsp;Fabiano P. Saggioro ,&nbsp;Rossana V.M. López ,&nbsp;Rodrigo A. Panepucci ,&nbsp;Carlos Curti ,&nbsp;Wilson A. Silva Jr ,&nbsp;Lewis J. Greene ,&nbsp;Andréia M. Leopoldino","doi":"10.1016/j.bbacli.2016.11.001","DOIUrl":"10.1016/j.bbacli.2016.11.001","url":null,"abstract":"<div><h3>Background</h3><p>MicroRNAs (miRNAs or miRs) are post-transcriptional regulators of eukaryotic cells and knowledge of differences in miR levels may provide new approaches to diagnosis and therapy.</p></div><div><h3>Methods</h3><p>The present study measured the levels of nine miRs in head and neck squamous cell carcinomas (HNSCC) and determined whether clinical pathological features are associated with differences in miR levels. SET (I2PP2A) and PTEN protein levels were also measured, since their levels can be regulated by miR-199b and miR-21, respectively. Nine miRs (miR-15a, miR-21, miR-29b, miR-34c, miR-100, miR-125b, miR-137, miR-133b and miR-199b) were measured by real time qRT-PCR in HNSCC samples from 32 patients and eight resection margins. SET (I2PP2A) and PTEN protein levels were estimated by immunohistochemistry in paired HNSCC tissues and their matched resection margins.</p></div><div><h3>Results</h3><p>In HNSCC, the presence of lymph node invasion was associated with low miR-15a, miR-34c and miR-199b levels, whereas the presence of perineural invasion was associated with low miR-199b levels. In addition, miR-21 levels were high whereas miR-100 and miR-125b levels were low in HNSCC compared to the resection margins. When HNSCC line HN12, with or without knockdown of SET, were transfected with miR-34c inhibitor or miR-34c mimic, the miR-34c inhibitor increased cell invasion capacity while miR-34c mimic decreased the cell invasion.</p></div><div><h3>Conclusions</h3><p>We showed that the levels of specific miRs in tumor tissue can provide insight into the maintenance and progression of HNSCC.</p></div><div><h3>General significance</h3><p>MiRNAs are up- or down-regulated during cancer development and progression; they can be prognosis markers and therapeutic targets in HNSCC.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54182183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 22
Altered expression of intracellular Toll-like receptors in peripheral blood mononuclear cells from patients with alopecia areata 斑秃患者外周血单个核细胞细胞内toll样受体表达的改变
BBA clinical Pub Date : 2016-06-01 DOI: 10.1016/j.bbacli.2016.03.006
Abdullateef A. Alzolibani , Zafar Rasheed , Ghada Bin Saif , Mohammed S. Al-Dhubaibi , Ahmad A. Al Robaee
{"title":"Altered expression of intracellular Toll-like receptors in peripheral blood mononuclear cells from patients with alopecia areata","authors":"Abdullateef A. Alzolibani ,&nbsp;Zafar Rasheed ,&nbsp;Ghada Bin Saif ,&nbsp;Mohammed S. Al-Dhubaibi ,&nbsp;Ahmad A. Al Robaee","doi":"10.1016/j.bbacli.2016.03.006","DOIUrl":"10.1016/j.bbacli.2016.03.006","url":null,"abstract":"<div><h3>Background</h3><p>Toll-like receptors (TLRs) are pattern-recognition-receptors that sense a variety of pathogens and initiation of innate and adaptive immune responses. This study was undertaken to investigate the expression of TLRs in peripheral blood-mononuclear cells (PBMCs) of AA patients and to determine whether TLR-mediated inflammatory signals are important for the perspective of AA management.</p></div><div><h3>Methods</h3><p>Gene expression of TLRs and T-helper (Th) type-1, Th-2, Th-17 and regulatory T-cell cytokines in PBMCs was quantified by TaqMan Assays. Production of these cytokines in serum samples was determined by sandwich ELISAs.</p></div><div><h3>Results</h3><p>All TLRs (TLRs 1–10) were expressed in PBMCs of AA patients. Importantly intracellular TLRs (TLRs 3, 7, 8 and 9) were significantly up-regulated in AA patients as compared with controls (p<!--> <!-->&lt;<!--> <!-->0.05). Interleukin (IL)-2, TNF-α, and IL-17A gene expression in patients' PBMCs and their secretion in patients' sera were significantly higher as compared with their respective controls (p<!--> <!-->&lt;<!--> <!-->0.05). Whereas, TGF-β gene expression in patients' PBMCs and TGF-β protein level in patients' sera were significantly lower as compared with their controls (p<!--> <!-->&lt;<!--> <!-->0.05).</p></div><div><h3>Conclusion</h3><p>This is the first report that shows the comprehensive expression profile of TLRs in AA patients. We conclude that up-regulated expression of intracellular TLRs in PBMCs of AA patients may play an active role in abnormal regulation of Th-1, Th-17 and regulatory T-cell cytokines in alopecia areata.</p></div><div><h3>General significance</h3><p>Targeting of TLRs and their associated inflammatory signaling will open new areas of research; this may lead to the development of novel therapeutic targets for the treatment of AA or other skin disorders.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.03.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34433840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Glioblastomas with copy number gains in EGFR and RNF139 show increased expressions of carbonic anhydrase genes transformed by ENO1 EGFR和RNF139拷贝数增加的胶质母细胞瘤显示ENO1转化的碳酸酐酶基因表达增加
BBA clinical Pub Date : 2016-06-01 DOI: 10.1016/j.bbacli.2015.11.001
Marie E. Beckner , Ian F. Pollack , Mary L. Nordberg , Ronald L. Hamilton
{"title":"Glioblastomas with copy number gains in EGFR and RNF139 show increased expressions of carbonic anhydrase genes transformed by ENO1","authors":"Marie E. Beckner ,&nbsp;Ian F. Pollack ,&nbsp;Mary L. Nordberg ,&nbsp;Ronald L. Hamilton","doi":"10.1016/j.bbacli.2015.11.001","DOIUrl":"10.1016/j.bbacli.2015.11.001","url":null,"abstract":"<div><h3>Background</h3><p>Prominence of glycolysis in glioblastomas may be non-specific or a feature of oncogene-related subgroups (i.e. amplified <em>EGFR</em>, etc.). Relationships between amplified oncogenes and expressions of metabolic genes associated with glycolysis, directly or indirectly via pH, were therefore investigated.</p></div><div><h3>Methods</h3><p>Using multiplex ligation-dependent probe amplification, copy numbers (CN) of 78 oncogenes were quantified in 24 glioblastomas. Related expressions of metabolic genes encoding lactate dehydrogenases (<em>LDHA</em>, <em>LDHC</em>), carbonic anhydrases (<em>CA3</em>, <em>CA12</em>), monocarboxylate transporters (<em>SLC16A3</em> or <em>MCT4</em>, <em>SLC16A4</em> or <em>MCT5</em>), ATP citrate lyase (<em>ACLY</em>), glycogen synthase1 (<em>GYS1</em>), hypoxia inducible factor-1A (<em>HIF1A</em>), and enolase1 (<em>ENO1</em>) were determined in 22 by RT-qPCR. To obtain supra-glycolytic levels and adjust for heterogeneity, concurrent <em>ENO1</em> expression was used to mathematically transform the expression levels of metabolic genes already normalized with delta-delta crossing threshold methodology.</p></div><div><h3>Results</h3><p>Positive correlations with <em>EGFR</em> occurred for all metabolic genes. Significant differences (Wilcoxon Rank Sum) for oncogene CN gains in tumors of at least 2.00-fold versus less than 2.00-fold occurred for <em>EGFR</em> with <em>CA3</em>'s expression (<em>p</em> <!-->&lt;<!--> <!-->0.03) and for <em>RNF139</em> with <em>CA12</em> (<em>p</em> <!-->&lt;<!--> <!-->0.004). Increased CN of <em>XIAP</em> associated negatively. Tumors with less than 2.00-fold CN gains differed from those with gains for <em>XIAP</em> with <em>CA12</em> (<em>p</em> <!-->&lt;<!--> <!-->0.05). Male gender associated with <em>CA12</em> (<em>p</em> <!-->&lt;<!--> <!-->0.05).</p></div><div><h3>Conclusions</h3><p>Glioblastomas with CN increases in <em>EGFR</em> had elevated <em>CA3</em> expression. Similarly, tumors with <em>RNF149</em> CN gains had elevated <em>CA12</em> expression.</p></div><div><h3>General significance</h3><p>In larger studies, subgroups of glioblastomas may emerge according to oncogene-related effects on glycolysis, such as control of pH via effects on carbonic anhydrases, with prognostic and treatment implications.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54180177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Involvement of mirror neuron system in prodromal Alzheimer's disease 镜像神经元系统在前驱阿尔茨海默病中的作用
BBA clinical Pub Date : 2016-06-01 DOI: 10.1016/j.bbacli.2015.12.001
D.V. Moretti
{"title":"Involvement of mirror neuron system in prodromal Alzheimer's disease","authors":"D.V. Moretti","doi":"10.1016/j.bbacli.2015.12.001","DOIUrl":"10.1016/j.bbacli.2015.12.001","url":null,"abstract":"<div><h3>Background</h3><p>Mirror neurons have been localized in several locations, including the inferior parietal lobule (IPL). Increase of EEG alpha3/alpha2 frequency power ratio has been detected in mild cognitive impairment (MCI) subjects who will convert in Alzheimer's disease (AD). We investigated the association of alpha3/alpha2 frequency power ratio with cortical thickness in IPL in MCI subjects.</p></div><div><h3>Methods</h3><p>74 adult subjects with MCI underwent EEG recording and high resolution MRI. Alpha3/alpha2 frequency power ratio as well as cortical thickness were computed for each subject. Three MCI groups were obtained according to increasing tertile values of alpha3/alpha2 ratio. Difference of cortical thickness among the groups was estimated.</p></div><div><h3>Results</h3><p>Higher alpha3/alpha2 frequency power ratio group had wider cortical thinning than other groups, mapped on the IPL, supramarginal gyrus and precuneus bilaterally.</p></div><div><h3>Conclusions</h3><p>High EEG alpha3/alpha2 frequency power ratio was associated with atrophy of IPL areas in MCI subjects.</p></div><div><h3>General significance</h3><p>The scientific hypothesis is divided into the following main points: 1) the theoretical background considering two recent theories, an evolutionary perspective theory and the theory of mind (ToM), which both track a possible relationship between prodromal AD and mirror system; 2) the relationship has been focused on the prodromal stage of Alzheimer's disease, that is a peculiar and very debated phase of the disease itself; and 3) not a generical relationship, but a focused anatomo-functional association has been proposed.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Prolonged activation of human islet cannabinoid receptors in vitro induces adaptation but not dysfunction 人类胰岛大麻素受体在体外的长期激活诱导适应,但不功能障碍
BBA clinical Pub Date : 2016-06-01 DOI: 10.1016/j.bbacli.2016.03.009
Alonso Vilches-Flores , Zara Franklin , Astrid C. Hauge-Evans , Bo Liu , Guo C. Huang , Pratik Choudhary , Peter M. Jones , Shanta J. Persaud
{"title":"Prolonged activation of human islet cannabinoid receptors in vitro induces adaptation but not dysfunction","authors":"Alonso Vilches-Flores ,&nbsp;Zara Franklin ,&nbsp;Astrid C. Hauge-Evans ,&nbsp;Bo Liu ,&nbsp;Guo C. Huang ,&nbsp;Pratik Choudhary ,&nbsp;Peter M. Jones ,&nbsp;Shanta J. Persaud","doi":"10.1016/j.bbacli.2016.03.009","DOIUrl":"10.1016/j.bbacli.2016.03.009","url":null,"abstract":"<div><h3>Background</h3><p>Although in vivo studies have implicated endocannabinoids in metabolic dysfunction, little is known about direct, chronic activation of the endocannabinoid system (ECS) in human islets. Therefore, this study investigated the effects of prolonged exposure to cannabinoid agonists on human islet gene expression and function.</p></div><div><h3>Methods</h3><p>Human islets were maintained for 2 and 5<!--> <!-->days in the absence or presence of CB1r (ACEA) or CB2r (JWH015) agonists. Gene expression was quantified by RT-PCR, hormone levels by radioimmunoassay and apoptosis by caspase activities.</p></div><div><h3>Results</h3><p>Human islets express an ECS, with mRNAs encoding the biosynthetic and degrading enzymes NAPE-PLD, FAAH and MAGL being considerably more abundant than DAGLα, an enzyme involved in 2-AG synthesis, or CB1 and CB2 receptor mRNAs. Prolonged activation of CB1r and CB2r altered expression of mRNAs encoding ECS components, but did not have major effects on islet hormone secretion. JWH015 enhanced insulin and glucagon content at 2<!--> <!-->days, but had no effect after 5<!--> <!-->days. Treatment with ACEA or JWH015 for up to 5<!--> <!-->days did not have marked effects on islet viability, as assessed by morphology and caspase activities.</p></div><div><h3>Conclusions</h3><p>Maintenance of human islets for up to 5<!--> <!-->days in the presence of CB1 and CB2 receptor agonists causes modifications in ECS element gene expression, but does not have any major impact on islet function or viability.</p></div><div><h3>General Significance</h3><p>These data suggest that the metabolic dysfunction associated with over-activation of the ECS in obesity and diabetes in humans is unlikely to be secondary to impaired islet function.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.03.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34433841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder 血液代谢组学分析确定了双相情感障碍中柠檬酸循环、尿素循环和氨基酸代谢的异常
BBA clinical Pub Date : 2016-06-01 DOI: 10.1016/j.bbacli.2016.03.008
Noriko Yoshimi , Takashi Futamura , Keiji Kakumoto , Alireza M. Salehi , Carl M. Sellgren , Jessica Holmén-Larsson , Joel Jakobsson , Erik Pålsson , Mikael Landén , Kenji Hashimoto
{"title":"Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder","authors":"Noriko Yoshimi ,&nbsp;Takashi Futamura ,&nbsp;Keiji Kakumoto ,&nbsp;Alireza M. Salehi ,&nbsp;Carl M. Sellgren ,&nbsp;Jessica Holmén-Larsson ,&nbsp;Joel Jakobsson ,&nbsp;Erik Pålsson ,&nbsp;Mikael Landén ,&nbsp;Kenji Hashimoto","doi":"10.1016/j.bbacli.2016.03.008","DOIUrl":"10.1016/j.bbacli.2016.03.008","url":null,"abstract":"<div><h3>Background</h3><p>Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD.</p></div><div><h3>Methods</h3><p>We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n<!--> <!-->=<!--> <!-->54) and age-matched male healthy controls (n<!--> <!-->=<!--> <!-->39).</p></div><div><h3>Results</h3><p>After multivariate logistic regression, serum levels of pyruvate, <em>N</em>-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, <em>N</em>-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate.</p></div><div><h3>Conclusions</h3><p>The metabolomics analysis demonstrated altered serum levels of pyruvate, <em>N</em>-acetylglutamic acid, β-alanine, serine, and arginine in BD patients.</p></div><div><h3>General significance</h3><p>The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.03.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34433843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 72
TCF7L2 polymorphism is associated with low nitric oxide release, endothelial dysfunction and enhanced inflammatory response after myocardial infarction TCF7L2多态性与心肌梗死后一氧化氮释放低、内皮功能障碍和炎症反应增强有关
BBA clinical Pub Date : 2016-06-01 DOI: 10.1016/j.bbacli.2016.03.010
Riobaldo Cintra , Filipe A. Moura , Luiz S.F. Carvalho , Mauricio Daher , Simone N. Santos , Ana P.R. Costa , Valeria N. Figueiredo , Joalbo M. Andrade , Francisco A.R. Neves , Jose C. Quinaglia e Silva , Andrei C. Sposito , on behalf of the Brasília Heart Study Group
{"title":"TCF7L2 polymorphism is associated with low nitric oxide release, endothelial dysfunction and enhanced inflammatory response after myocardial infarction","authors":"Riobaldo Cintra ,&nbsp;Filipe A. Moura ,&nbsp;Luiz S.F. Carvalho ,&nbsp;Mauricio Daher ,&nbsp;Simone N. Santos ,&nbsp;Ana P.R. Costa ,&nbsp;Valeria N. Figueiredo ,&nbsp;Joalbo M. Andrade ,&nbsp;Francisco A.R. Neves ,&nbsp;Jose C. Quinaglia e Silva ,&nbsp;Andrei C. Sposito ,&nbsp;on behalf of the Brasília Heart Study Group","doi":"10.1016/j.bbacli.2016.03.010","DOIUrl":"10.1016/j.bbacli.2016.03.010","url":null,"abstract":"<div><h3>Backgound</h3><p>The favorable effects of insulin during myocardial infarction (MI) remain unclear due to the divergence between mechanistic studies and clinical trials of exogenous insulin administration. The rs7903146 polymorphism of the <em>transcription factor 7-like 2</em> (TCF7L2) gene is associated with attenuated insulin secretion.</p></div><div><h3>Methods</h3><p>In non-diabetic patients with ST-elevation MI (STEMI), using such a model of genetically determined down-regulation of endogenous insulin secretion we investigated the change in plasma insulin, C-peptide, interleukin-2 (IL-2), C-reactive protein (CRP), and nitric oxide (NOx) levels between admission (D1) and the fifth day after MI (D5). Coronary angiography and flow-mediated dilation (FMD) were performed at admission and 30<!--> <!-->days after MI, respectively. Homeostasis Model Assessment estimated insulin secretion (HOMA2%β) and insulin sensitivity (HOMA2%S).</p></div><div><h3>Results</h3><p>Although glycemia did not differ between genotypes, carriers of the T-allele had lower HOMA2%β and higher HOMA2%S at both D1 and D5. As compared with non-carriers, T-allele carriers had higher plasma IL-2 and CRP at D5, higher intracoronary thrombus grade, lower FMD and NOx change between D1 and D5 and higher 30-day mortality.</p></div><div><h3>Conclusion</h3><p>In non-diabetic STEMI patients, the rs7903146 <em>TCF7L2</em> gene polymorphism is associated with lower insulin secretion, worse endothelial function, higher coronary thrombotic burden, and higher short-term mortality.</p></div><div><h3>General significance</h3><p>During the acute phase of MI, a lower capacity of insulin secretion may influence clinical outcome.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.03.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34510046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
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