Database : MEDLINE
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[PMID]: 29524758
[Au] Autor:Shahmohammadi S; Sahraian MA; Shahmohammadi A; Doosti R; Zare-Mirzaie A; Naser Moghadasi A
[Ad] Address:MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
[Ti] Title:A presentation of ulcerative colitis after rituximab therapy in a patient with multiple sclerosis and literature review.
[So] Source:Mult Scler Relat Disord;22:22-26, 2018 Mar 01.
[Is] ISSN:2211-0356
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Multiple sclerosis (MS) is one of the most important demyelinating diseases that affects the central nervous system. Its treatment often involves a long-term disease modifying therapy. According to some studies, the prevalence of autoimmune disorders, such as autoimmune hepatitis (AIH) and ulcerative colitis (UC) is higher in MS patients than in the normal population. There are also few studies that have reported the onset of UC after rituximab therapy. The present study presents a report of a 31-years old female patient suffering from aggressive multiple sclerosis, which developed into autoimmune hepatitis during the MS therapy. Thereafter, she received rituximab for the treating both MS and AIH. One week after the third cycle of rituximab (6 doses of 1000 mg), she experienced abdominal pain, fever, and severe bloody diarrhea; finally, she was diagnosed with ulcerative colitis (UC). It seems that the administration of certain immunomodulators or immunosuppressive drugs may have a main role in the exacerbation of some autoimmune diseases.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

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[PMID]: 29524654
[Au] Autor:Aktories K; Papatheodorou P; Schwan C
[Ad] Address:Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Albertstr. 25, 79104 Freiburg, Germany; Centre for Biological Signalling Studies (BIOSS), University of Freiburg, 79104 Freiburg, Germany. Electronic address: klaus.aktories@pharmakol.uni-freiburg.de.
[Ti] Title:Binary Clostridium difficile toxin (CDT) - A virulence factor disturbing the cytoskeleton.
[So] Source:Anaerobe;, 2018 Mar 07.
[Is] ISSN:1095-8274
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Clostridium difficile infection causes antibiotics-associated diarrhea and pseudomembranous colitis. Major virulence factors of C. difficile are the Rho-glucosylating toxins TcdA and TcdB. In addition, many, so-called hypervirulent C. difficile strains produce the binary actin-ADP-ribosylating toxin CDT. CDT causes depolymerization of F-actin and rearrangement of the actin cytoskeleton. Thereby, many cellular functions, which depend on actin, are altered. CDT disturbs the dynamic balance between actin and microtubules in target cells. The toxin increases microtubule polymerization and induces the formation of microtubule-based protrusions at the plasma membrane of target cells. Moreover, CDT causes a redistribution of vesicles from the basolateral side to the apical side, where extracellular matrix proteins are released. These processes may increase the adherence of clostridia to target cells. Here, we review the effects of the action of CDT on the actin cytoskeleton and on the microtubule system.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  3 / 96857 MEDLINE  
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[PMID]: 29524405
[Au] Autor:Nan Z; Fan H; Tang Q; Zhang M; Xu M; Chen Q; Liu Y; Dong Y; Wu H; Deng S
[Ad] Address:Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
[Ti] Title:Dual expression of CXCR4 and IL-35 enhances the therapeutic effects of BMSCs on TNBS-induced colitis rats through expansion of Tregs and suppression of Th17 cells.
[So] Source:Biochem Biophys Res Commun;, 2018 Mar 07.
[Is] ISSN:1090-2104
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for the treatment of inflammatory bowel disease (IBD) owing to the immunosuppressive property and tissue healing potential. The balance of Treg/Th17 plays a crucial part in BMSC-mediated immunosuppression. Interleukin (IL)-35 is a newly identified anti-inflammatory cytokine required for the expansion of regulatory T cells (Tregs) and suppression of Th17 cells differentiation. It could amplify the immunosuppressive property of BMSCs by transfecting into BMSCs. However, the reparative capability of BMSCs in vivo is limited partly due to barren efficiency of BMSCs homing to inflamed colons. Up-regulation of CXC chemokine receptor 4 (CXCR4) expression on BMSCs is supposed to affect the directional homing of implanted BMSCs via stromal-derived factor-1 (SDF-1). In this study, by introducing lentivirus-mediated CXCR4 and IL-35 genes to modify rat BMSCs, we observed promoted migration ability and strengthened immunomodulatory activity of the genetically engineering BMSCs. These results suggest that the modification of BMSCs by dual expression of CXCR4 and IL-35 may provide an effective therapeutic strategy of BMSCs for IBD.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  4 / 96857 MEDLINE  
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[PMID]: 29517899
[Au] Autor:Mondal S; Parelkar SS; Nagar M; Thompson PR
[Ti] Title:Photochemical Control of Protein Arginine Deiminase (PAD) Activity.
[So] Source:ACS Chem Biol;, 2018 Mar 08.
[Is] ISSN:1554-8937
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Protein Arginine deiminases (PADs) play an important role in the pathogenesis of various diseases, including rheumatoid arthritis, multiple sclerosis, lupus, ulcerative colitis and breast cancer. Therefore, the development of PAD-inhibitors has drawn significant research interest in recent years. Herein, we describe the development of the first photoswitchable PAD-inhibitors. These compounds possess an azobenzene photoswitch to optically control PAD activity. Screening of a series of inhibitors structurally similar to BB-Cl-Amidine afforded compounds 1 and 2 as the most promising candidates for the light-controlled inhibition of PAD2; the cis-isomer of 1 is 10-fold more potent than its trans-isomer, whereas the trans-isomer of 2 is 45-fold more potent than the corresponding cis-isomer. The altered inhibitory potency upon photoisomerization has been confirmed in a competitive activity-based protein profiling (ABPP) assay. Further investigations indicate that the trans-isomer of 2 is an irreversible inhibitor, whereas the cis-isomer acts as a competitive inhibitor. In cells, the trans-isomer of compound 1 is completely inactive, whereas the cis-isomer inhibits histone H3-citrullination in a dose-dependent manner. Taken together, 1 serves as the foundation for developing photopharmaceuticals that can be activated at the desired tissue, using light, to treat diseases where PAD activity is dysregulated.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:Publisher
[do] DOI:10.1021/acschembio.8b00053

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[PMID]: 29462738
[Au] Autor:Azizi S; Al-Rubaye H; Turki MAA; Siddiqui MRS; Shanmuganandan AP; Ehsanullah B; Brar R; Abulafi AM
[Ad] Address:St. George's, University of London, Department of Medicine, Cranmer Terrace, SW17 0RE, UK.
[Ti] Title:Detecting dysplasia using white light endoscopy or chromoendoscopy in ulcerative colitis patients without primary sclerosing cholangitis: A systematic review and meta-analysis.
[So] Source:Int J Surg;52:180-188, 2018 Feb 17.
[Is] ISSN:1743-9159
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Endoscopic examinations are a vital diagnostic tool for dysplasia. Establishing the precision of different modes of examination is essential due to the disparate pick-up rates of dysplasia. OBJECTIVE: The aim of this article was to establish the pick-up rates of dysplastic or cancerous lesions using white light endoscopy (WLE) and random/targeted biopsies, or chromoendoscopy (CE), in patients with ulcerative colitis (UC) without primary sclerosing (PSC) or Crohn's disease (CD). DATA SOURCES: A systematic review to identify all studies up to November 2017, without language restriction, was conducted from PubMed, the Cochrane Controlled Trials Register (1960-2017), MEDLINE, CINAHL and EMBASE (1981-2017). MeSH and text word terms used included "ulcerative colitis", "dysplasia", "random biopsy", "targeted biopsy", "colonoscopy", "white light", and "chromoendoscopy". Further searches were performed using the bibliographies of these articles. STUDY SELECTION: All studies reporting on colonoscopy detection rates of dysplasia and cancers in UC without involvement of PSC or CD were included. There was no age restriction to include patients. DATA EXTRACTION: Outcome data were extracted by 2 authors independently using outcome measures defined a priori. Quality assessment was performed using the Newcastle-Ottawa scales. DATA SYNTHESIS: Data were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. The pooled overall pick-up rate of dysplastic/cancerous lesions on WLE random biopsies was 5.6% [Event rate 0.06 (0.01, 0.23), df = 4, I2 = 94%]. Using a combined random and targeted approach with WLE the incidence was 5.1% [Event rate 0.05 (0.03, 0.09), df = 4, I2 = 96%]. One study reported on CE and found a 7% pick-up rate for dysplastic lesions. CONCLUSIONS: Endoscopic examination of UC patients without PSC identifies dysplastic or cancerous lesions in 5-7% of cases. WLE and random biopsies may pick-up a similar number of lesions to targeted biopsies, however the number of biopsies may need to be greater to achieve this equivalence. CE has a slightly higher pick-up rate. Further comparative studies are required to strengthen the body of evidence.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  6 / 96857 MEDLINE  
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[PMID]: 29410110
[Au] Autor:Poh S; Chelvam V; Ayala-Lpez W; Putt KS; Low PS
[Ad] Address:College of Engineering and Science - Chemistry, Louisiana Tech University, Ruston, LA.
[Ti] Title:Selective liposome targeting of folate receptor positive immune cells in inflammatory diseases.
[So] Source:Nanomedicine;14(3):1033-1043, 2018 Feb 01.
[Is] ISSN:1549-9642
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Activated macrophages play a key role in the development and maintenance of inflammatory diseases such as atherosclerosis, lupus, psoriasis, rheumatoid arthritis, ulcerative colitis, and many others. These activated macrophages, but not resting or quiescent macrophages highly up-regulate folate receptor beta (FR-). This differential expression of FR- provides a mechanism to selectively deliver imaging and therapeutic agents utilizing folate as a targeting molecule. In an effort to determine whether inflammatory diseases can be targeted utilizing a folate-linked nanosize carrier, a PEG-coated liposome was prepared that incorporated a folate conjugated PEG that also could transport imaging or therapeutic cargo. We demonstrate that these folate-liposomes specifically bind to folate receptor positive cells and accumulate at sites of inflammation in mouse models of colitis and atherosclerosis. These two animal models show that folate-targeted liposomes could be successfully utilized to deliver fluorescent molecules and an anti-inflammatory drug (betamethasone) for diagnostic and therapeutic applications.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  7 / 96857 MEDLINE  
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[PMID]: 29353017
[Au] Autor:Naeem M; Oshi MA; Kim J; Lee J; Cao J; Nurhasni H; Im E; Jung Y; Yoo JW
[Ad] Address:College of Pharmacy, Pusan National University, Busan, South Korea.
[Ti] Title:pH-triggered surface charge-reversal nanoparticles alleviate experimental murine colitis via selective accumulation in inflamed colon regions.
[So] Source:Nanomedicine;14(3):823-834, 2018 Jan 17.
[Is] ISSN:1549-9642
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:In this study, we developed pH-triggered surface charge-reversal lipid nanoparticles (LNPs), loaded with budesonide, which could precisely deliver the drug to inflamed colon segments for the treatment of ulcerative colitis. Polyethyleneimine (PEI) was used to render LNPs cationic (PEI-LNPs), and Eudragit S100 (ES) was coated on PEI-LNPs to obtain pH-triggered charge-reversal LNPs (ES-PEI-LNPs). ES coating avoided a burst drug release under acidic conditions mimicking the stomach and early small intestine environments and showed a sustained release in the colon. The surface charge of ES-PEI-LNPs switched from negative to positive under colonic conditions owing to pH-triggered removal of the ES coating. Bioimaging of the mouse gastrointestinal tract and confocal analysis of colon tissues revealed that ES-PEI-LNPs selectively accumulated in an inflamed colon. Furthermore, ES-PEI-LNPs mitigated experimental colitis in mice. These results suggest that the pH-triggered charge-reversal LNPs could be a promising drug carrier for ulcerative colitis therapy and other colon-targeted treatments.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  8 / 96857 MEDLINE  
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[PMID]: 29341591
[Au] Autor:Nemmara VV; Subramanian V; Muth A; Mondal S; Salinger AJ; Maurais AJ; Tilvawala R; Weerapana E; Thompson PR
[Ad] Address:Department of Biochemistry and Molecular Pharmacology, UMass Medical School , 364 Plantation Street, Worcester, Massachusetts 01605, United States.
[Ti] Title:The Development of Benzimidazole-Based Clickable Probes for the Efficient Labeling of Cellular Protein Arginine Deiminases (PADs).
[So] Source:ACS Chem Biol;, 2018 Feb 01.
[Is] ISSN:1554-8937
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Citrullination is the post-translational hydrolysis of peptidyl-arginines to form peptidyl-citrulline, a reaction that is catalyzed by the protein arginine deiminases (PADs), a family of calcium-regulated enzymes. Aberrantly increased protein citrullination is associated with a slew of autoimmune diseases (e.g., rheumatoid arthritis (RA), multiple sclerosis, lupus, and ulcerative colitis) and certain cancers. Given the clear link between increased PAD activity and human disease, the PADs are therapeutically relevant targets. Herein, we report the development of next generation cell permeable and "clickable" probes (BB-Cl-Yne and BB-F-Yne) for covalent labeling of the PADs both in vitro and in cell-based systems. Using advanced chemoproteomic technologies, we also report the off targets of both BB-Cl-Yne and BB-F-Yne. The probes are highly specific for the PADs, with relatively few off targets, especially BB-F-Yne, suggesting the preferential use of the fluoroacetamidine warhead in next generation irreversible PAD inhibitors. Notably, these compounds can be used in a variety of modalities, including the identification of off targets of the parent compounds and as activity-based protein profiling probes in target engagement assays to demonstrate the efficacy of PAD inhibitors.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:Publisher
[do] DOI:10.1021/acschembio.7b00957

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[PMID]: 29223444
[Au] Autor:Ungar B; Kopylov U; Yavzori M; Fudim E; Picard O; Lahat A; Coscas D; Waterman M; Haj-Natour O; Orbach-Zingboim N; Mao R; Chen M; Chowers Y; Eliakim R; Ben-Horin S
[Ad] Address:Department of Gastroenterology, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Electronic address: bellageyshis@gmail.com.
[Ti] Title:Association of Vedolizumab Level, Anti-Drug Antibodies, and α47 Occupancy With Response in Patients With Inflammatory Bowel Diseases.
[So] Source:Clin Gastroenterol Hepatol;, 2017 Dec 07.
[Is] ISSN:1542-7714
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND & AIMS: There are few data available on the real-life pharmacokinetic and pharmacodynamics features of vedolizumab, a monoclonal antibody against integrin α47. We performed a prospective study of patients with inflammatory bowel diseases (IBDs) treated with vedolizumab to determine serum drug concentrations, formation of antivedolizumab antibodies (AVAs), and integrin α47 saturation. METHODS: We performed a prospective study of 106 patients with IBD (67 with Crohn's disease and 39 with ulcerative colitis) treated with vedolizumab from September 2014 through March 2017 at 2 tertiary medical centers in Israel. Clinical data and serum samples were collected before and during induction and maintenance therapy. Clinical remission was defined as Harvey-Bradshaw index scores below 5 or as Simple Clinical Colitis Activity Index scores of 3 or less. We measured serum levels of vedolizumab, AVAs, and markers of inflammation. Peripheral blood mononuclear cells were obtained from some patients at designated trough time points and CD3+ CD45RO+ T cells were isolated from 36 samples. Cells were incubated with fluorescent-conjugated vedolizumab and flow cytometry was used to quantify α47 integrin saturation. We also performed flow cytometry analyses of CD3+ CD45RO+ lamina propria T cells isolated from intestinal mucosa of patients without IBD (non-IBD controls, n= 6), patients with IBD not treated with vedolizumab (untreated IBD controls, n= 8), and patients with IBD treated with vedolizumab (n= 15). RESULTS: Clinical remission was achieved by 48 of 106 patients (45%) by week 6 and 50 of 106 patients (48%) by week 14 of treatment. The median level of vedolizumab at week 6 was higher in patients in clinical remission (40.2 g/mL) than in patients with active disease (29.7 g/mL; P= .05). The median serum level of vedolizumab was significantly higher in patients with a normal level of C-reactive protein (21.8 g/mL vedolizumab) vs the level in those with a high level of C-reactive protein (11.9 g/mL vedolizumab) during maintenance treatment (P= .0006). The other clinical outcomes measured were not associated with median serum level of vedolizumab at any time point examined. AVAs were detected in 17% of patients during induction therapy and 3% of patients during maintenance therapy, but did not correlate with clinical outcomes. Flow-cytometry analysis of peripheral blood memory T cells (n= 36) showed near-complete occupancy of α47 integrin at weeks 2 and 14 and during the maintenance phase, regardless of response status or drug levels. Most intestinal CD3+CD45RO+ memory T cells of healthy and IBD controls expressed α47 (72%; interquartile range, 56%-81%). In contrast, free α47 was detectable on only 5.6% of intestinal memory cells (interquartile range, 4.4%-11.2%) (P < .0001) from vedolizumab-treated patients, regardless of response. CONCLUSIONS: In a prospective study of real-life patients with IBD, we associated vedolizumab drug levels with remission and level of a marker of inflammation. Integrin α47 was blocked in almost all T cells from patients treated with vedolizumab, regardless of serum level of the drug or response to treatment. These findings indicate a need to explore alternative mechanisms that prevent response to vedolizumab.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  10 / 96857 MEDLINE  
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[PMID]: 29524119
[Au] Autor:Sarid O; Slonim-Nevo V; Schwartz D; Friger M; Sergienko R; Pereg A; Vardi H; Chernin E; Singer T; Greenberg D; Odes S; Israel IBD Research Nucleus (IIRN)
[Ad] Address:Spitzer Department of Social Work, Ben-Gurion University of the Negev, POB 653, 84105, Beer Sheva, Israel.
[Ti] Title:Differing Relationship of Psycho-Social Variables with Active Ulcerative Colitis or Crohn's Disease.
[So] Source:Int J Behav Med;, 2018 Mar 09.
[Is] ISSN:1532-7558
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:PURPOSE: How psycho-social variables affect the degree of disease activity in patients with ulcerative colitis (UC) or Crohn's disease (CD) is incompletely understood. Therefore, we measured and compared the impact of psycho-social variables on the active disease state in UC and CD. METHOD: One hundred and twenty-two UC and 305 CD patients with active disease completed questionnaires detailing their psychological symptoms, threatening experiences, disease-coping strategies, satisfaction with life, quality of life, and demographics. RESULTS: UC and CD patients were aged (mean, SD) 38.6 14.0 and 45.2 15.1years, respectively. The psychological symptom index (median, IQR) was greater in UC 1.24 (0.8) than CD 0.9 (0.8), p < 0.001. UC used more emotion-focused strategies, 24.5 (5.7) than CD, 23.0 (5.7), p < 0.03; problem-focused strategies, 16.4 (4.5) vs. 15.4 (4.2), p < 0.04; and dysfunctional strategies, 23.7 (5.7) vs. 22.0 (5.0), p < 0.01. UC activity correlated with gender, age, economic status, psychological symptoms, threatening experiences, all coping strategies, satisfaction with life, and quality of life (p < 0.02-0.001). CD activity correlated with economic status, psychological symptoms, threatening experiences, dysfunctional strategies, satisfaction with life, and quality of life (p < 0.05-0.001). UC activity was predicted by psychological symptoms (9.1% variance), economic status (6.9%), problem-focused strategies (4.2%), and threatening experiences (1.3%); CD activity by threatening experiences (5% variance) and psychological symptoms (4%). In path analysis, psychological symptoms and problem-focused strategies mediated the effects of economic status, age, and threatening experiences on UC activity. In CD, the dominant pathway was threatening experiences impacting on psychological symptoms. CONCLUSION: The impact of psycho-social variables on the active disease state differs between UC and CD, thus indicating a need for specifically tailored psychotherapies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher
[do] DOI:10.1007/s12529-018-9712-5


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