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Practical fecal calprotectin cut-off value for Japanese patients with ulcerative colitis

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World Journal of Gastroenterology 2018年第38期24卷 4384-4392页

作者： Jun Urushikubo Shunichi Yanai Shotaro Nakamura Keisuke Kawasaki Risaburo Akasaka Kunihiko Sato Yosuke Toya Kensuke Asakura Takahiro Gonai Tamotsu Sugai Takayuki Matsumoto division of Gastroenterology Department of Internal Medicine School of Medicine Iwate Medical University division of molecular Diagnostic Pathology Department of Pathology School of Medicine Iwate Medical University

AIM To determine appropriate fecal calprotectin cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with ulcerative colitis(UC). METHODS We performed a cross-sectional observational study of 131 Japanese patients with UC and measured fecal calprotectin levels by fluorescence enzyme immunoassay. The clinical activity of UC was assessed with the partial Mayo score(PMS). Relapse was defined as increase of PMS by 2 points or more in stool frequency or rectal bleeding subscore. The endoscopic and histologic activities of UC were evaluated in 50 patients within a 2-mo period from fecal sampling. Endoscopic activity was determined by Mayo endoscopic subscore, Rachmilewitz endoscopic index, and ulcerative colitis endoscopic index of severity. The histologic grade of inflammation was evaluated with biopsy specimens obtained from the endoscopically most severely inflamed site, according to the scheme by Matts grade and Riley's score.RESULTS Fecal calprotectin levels varied from 1-20783 μg/g. There was a significant correlation between the partial Mayo score and fecal calprotectin levels(r = 0.548, P < 0.001). In 50 patients who underwent colonoscopy with biopsy, levels were significantly correlated with the Mayo endoscopic subscore(r = 0.574, P < 0.001), Rachmilewitz endoscopic index(r = 0.628, P < 0.001), ulcerative colitis endoscopic index of severity(r = 0.613, P < 0.001), Riley's histologic score(r = 0.400, P = 0.006), and Matts grade(r = 0.586, P < 0.001). Receiver-operating characteristic analyses identified the best cut-off value for the prediction of endoscopic remission as 288 μg/g, with an area under the curve of 0.777 or 0.823, while that for histologic remission was 123 or 125 μg/g, with an AUC of 0.881 or 0918, respectively. Of the 131 study patients, 88 patients in clinical remission were followed up 6 mo. During the follow-up period, 19 patients relapsed. The best fecal calprotectin cut-off value for predicting relapse was 175 μg/g.CONCLUSION Fecal calprotectin is a

关键词： Ulcerative colitis Remission Mucosal healing Colonoscopy Histology Biomarker Feces Calprotectin

Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts

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Cellular & molecular Immunology 2010年第4期7卷 306-315页

作者： Sankar Bhattacharyya Dewan Md Sakib Hossain Suchismita Mohanty Gouri Sankar Sen Sreya Chattopadhyay Shuvomoy Banerjee Juni Chakraborty Kaushik Das Diptendra Sarkar Tanya Das Gaurisankar Sa division of molecular medicine Bose InstituteKolkataIndia

Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune evasion.CD81 cytotoxic T lymphocytes(CTLs)are involved in antigen-specific tumor destruction and CD41 T cells are essential for helping this CD81 T cell-dependent tumor eradication.Tumors often target and inhibit T-cell function to escape from immune surveillance.This dysfunction includes loss of effector and memory T cells,bias towards type 2 cytokines and expansion of T regulatory(Treg)cells.Curcumin has previously been shown to have antitumor activity and some research has addressed the immunoprotective potential of this plant-derived polyphenol in tumor-bearing hosts.Here we examined the role of curcumin in the prevention of tumor-induced dysfunction of T cell-based immune responses.We observed severe loss of both effector and memory T-cell populations,downregulation of type 1 and upregulation of type 2 immune responses and decreased proliferation of effector T cells in the presence of tumors.Curcumin,in turn,prevented this loss of T cells,expanded central memory T cell(TCM)/effector memory T cell(TEM)populations,reversed the type 2 immune bias and attenuated the tumor-induced inhibition of T-cell proliferation in tumor-bearing hosts.Further investigation revealed that tumor burden upregulated Treg cell populations and stimulated the production of the immunosuppressive cytokines transforming growth factor(TGF)-b and IL-10 in these cells.Curcumin,however,inhibited the suppressive activity of Treg cells by downregulating the production of TGF-b and IL-10 in these cells.More importantly,curcumin treatment enhanced the ability of effector T cells to kill cancer cells.Overall,our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses.

关键词： CD41/CD81 T cell Effector T cell T-regulatory cell FoxP3 Th1/Th2

Exploring pre-degenerative alterations in humans using induced pluripotent stem cell-derived dopaminergic neurons

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Neural Regeneration Research 2017年第7期12卷 1068-1070页

作者： Federica Bono Chiara Fiorentini division of Pharmacology Department of Molecular andTranslational Medicine University of Brescia Brescia Italy

Understanding the cellular and molecular mechanisms underlying human neurological disorders is hindered by both the complexity of the disorders and the lack of suitable experimental models recapitulating key pathological features of the disease.This is a crucial issue since a limited understanding of pathogenic mechanisms precludes the development of drugs counteracting the progression of the disease.Among neurological disorders,

关键词： in Exploring pre-degenerative alterations in humans using induced pluripotent stem cell-derived dopaminergic neurons stem DAT been that of cell PSC

Pancreatic acinar cell carcinoma: A review on molecular profiling of patient tumors

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World Journal of Gastroenterology 2017年第45期23卷 7945-7951页

作者： Ahmad Al-Hader Rami N Al-Rohil Haiyong Han Daniel Von Hoff division of Hematology/Oncology Indiana University School of Medicine Department of Pathology Vanderbilt University School of Medicine Molecular Medicine Division Translational Genomics Research Institute (TGen)

Pancreatic carcinomas with acinar differentiation are rare,accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma(PACC),pancreatoblastoma,and carcinomas of mixed differentiation. Patients with PACC have a prognosis better than pancreatic ductal adenocarcinomas but worse than pancreatic neuroendocrine tumors. Reports of overall survival range from 18 to 47 mo. A literature review on PACCs included comprehensive genomic profiling and whole exome sequencing on a series of more than 70 patients as well as other diagnostic studies including immunohistochemistry. Surgical resection of PACC is the preferred treatment for localized and resectable tumors. The efficacy of adjuvant treatment is unclear. Metastatic PACCs are generally not curable and treated with systemic chemotherapy. They are moderately responsive to chemotherapy with different regimens showing various degrees of response in case reports/series. Most of these regimens were developed to treat patients with pancreatic ductal adenocarcinomas or colorectal adenocarcinomas. Review of PACC's molecular profiling showed a number of gene alterations such as: SMAD4,BRAF,BRCA2,TP53,RB1,MEN1,JAK-1,BRCA-1,BRCA-2,and DNA mismatch repair abnormalities. PACCs had multiple somatic mutations with some targetable with available drugs. Therefore,molecular profiling of PACC should be an option for patients with refractory PACC.

关键词：胰腺的 acinar 房间癌分子的介绍指向的治疗

Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-α inhibitors(Anti-TNFα)

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World Journal of Gastroenterology 2018年第25期24卷 2764-2775页

作者： Brent L Cao Ahmad Qasem Robert C Sharp Latifa S Abdelli Saleh A Naser division of molecular Microbiology Burnett School of Biomedical Sciences College of Medicine University of Central Florida

AIM To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis(TB) infection in Crohn's disease(CD) patients treated with tumor necrosis factoralpha(TNFα) inhibitors.METHODS A meta-analysis of randomized, double-blind, placebocontrolled trials of TNFα inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction(EBC) enabling inclusions of studies reporting no TB infection cases in placebo and treatment groups was developed to estimate relative odds.RESULTS Twenty-three clinical trial studies were identified, including 5669 patients. Six TB infection cases were reported across 5 studies, all from patients receiving TNFα inhibitors. Eighteen studies reported no TB infection cases in placebo and TNFα inhibitor treatment arms. TB infection risk was significantly increased among patients receiving TNFα inhibitors, with a risk difference of 0.028(95%CI: 0.0011-0.055). The odds ratio was 4.85(95%CI: 1.02-22.99) with EBC and 5.85(95%CI: 1.13-30.38) without EBC.CONCLUSION The risk of TB infection is higher among CD patients receiving TNFα inhibitors. Understanding the immunopathogenesis of CD is crucial, since using TNFα inhibitors in these patients could favor mycobacterial infections, particularly Mycobacterium avium subspecies paratuberculosis, which ultimately could worsen their clinical condition.

关键词： Tuberculosis Tumor necrosis factor-alpha inhibitors Crohn’s Disease Meta-analysis Systematic review

中低危人群中动脉粥样硬化的患病率和分布情况:基于全身MR血管成像的研究

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国际医学放射学杂志 2018年第4期 478-479页

作者： M.A.Lambert J.R.Weir-McCall M.Salsano S.J.Gandy D.Levin 温小娟 division of molecular and Clinical medicine College of MedicineUniversity of Dundee

目的量化心血管疾病中低风险人群中无症状动脉粥样硬化的负担和分布情况。材料与方法前瞻性纳入2008年6月—2013年2月期间10年心血管疾病风险低于20%的1 528名参与者。利用双注射四站采集技术对受试者行3.0 T全身MR血管成像（MRA）检查... 详细信息

目的量化心血管疾病中低风险人群中无症状动脉粥样硬化的负担和分布情况。材料与方法前瞻性纳入2008年6月—2013年2月期间10年心血管疾病风险低于20%的1 528名参与者。利用双注射四站采集技术对受试者行3.0 T全身MR血管成像（MRA）检查。根据最大狭窄程度对31个动脉节段进行评分。对可评估的动脉节段的数量进行归纳校正以提供标准化的动脉粥样硬化评分（SAS）。采用多元线性回归方法评估危险因素对发生动脉粥样硬化的影响。结果共计1 513名受试者[男性577名（37.9%）,平均年龄53.5岁,范围40;3岁]完成实验。在46 903个潜在的可分析节段中有46 601（99.4%）个节段可分析统计。其中,2 468个节段（5%）显示狭窄,且1 649个节段（3.5%）狭窄程度<50%,484个节段（1.0%）狭窄程度≥50%。血管狭窄分布全身。747个受试者（49.4%）至少有一根血管狭窄,408个受试者（27.0%）有多根血管狭窄。在多元线性回归分析中,SAS与年龄（B=3.4;95%CI:2.61;.20）、心率（B=1.23;95%CI:0.51;.95）、收缩压（B=0.02;95%CI:0.01;.03）、吸烟状态（B=0.79;95%CI:0.44;.15）和社会经济状况（B=-0.06;95%CI:-0.10;0.02）(所有P<0.01)显著相关。结论全身MRA可以识别人群早期血管疾病。尽管在每一血管水平血管疾病的发病率都很低,但在低到中等心血管疾病风险的人群中个人水平血管病变仍很常见。

关键词：动脉粥样硬化血管成像 MR

Lactic control of tumor growth:a new role for an old metabolite

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3890-3891页

作者： Carolina E.Hagberg division of Cardiovascular medicine Department of Medicine SolnaKarolinska InstitutetStockholmSweden and 2 Center for Molecular MedicineKarolinska InstitutetStockholmSweden

In a recent study published in Nature,Liu and co-workers show that high lactate production by tumor cells promotes premature mitotic escape and further cell proliferation by facilitating the binding of Ubiquitin Conjugating Enzyme E2 C(UBE2C)to the anaphase promoting complex(APC/C).1 This is important as it suggests cancer metabolism not only to be a consequence of tumor growth,but also one of its drivers.Since its initial discovery over 200 years ago,lactate has sustained the interest of a wide range of research fields due to its significance as energy fuel,redox buffer and signaling molecule.2 High quantities of lactate are produced through glycolysis in muscle during exercise,through bacterial lactic acid fermentation,and perhaps most famously,by rapidly growing tumor cells.

关键词： metabolism sustained consequence

Defining A Global Map of Functional Group-based 3D Ligand-binding Motifs

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Genomics, Proteomics & Bioinformatics 2022年第4期20卷 765-779页

作者： Liu Yang Wei He Yuehui Yun Yongxiang Gao Zhongliang Zhu Maikun Teng Zhi Liang Liwen Niu School of Life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China division of molecular and Cellular Biophysics Hefei National Laboratory for Physical Sciences at the MicroscaleHefei 230026China

Uncovering conserved 3D protein–ligand binding patterns on the basis of functional groups(FGs)shared by a variety of small molecules can greatly expand our knowledge of protein–ligand interactions.Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature,large-scale identification and evaluation of FG-based 3D binding motifs are still lacking.Here,we propose a computational method,Automatic FG-based Three-dimensional Motif Extractor(AFTME),for automatic mapping of 3D motifs to different FGs of a specific ligand.Applying our method to 233 naturally-occurring ligands,we define 481 FG-binding motifs that are highly conserved across different ligand-binding pockets.Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs.Combinations of FG-binding motifs facilitate the binding of proteins to a wide spectrum of ligands with various binding affinities.Finally,we show that our FG–motif map can be used to nominate FGs that potentially bind to specific drug targets,thus providing useful insights and guidance for rational design of small-molecule drugs.

关键词： Protein–ligand interaction Functional group Binding motif Computational method Drug design

Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids

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Acta Pharmaceutica Sinica B 2015年第2期5卷 129-134页

作者： Courtney B.Ferrebee Paul A.Dawson Department of Pediatrics Division of Gastroenterology Hepatology and Nutrition Emory University molecular medicine Graduate Program Wake Forest School of Medicine

The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size,and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor(FXR)and the G-protein-coupled bile acid receptor(TGR5).

关键词： Bile acids Liver Intestine Transporters Lipid metabolism Energy homeostasis