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https://www.readbyqxmd.com/read/28923942/identification-of-sialic-acid-binding-function-for-the-middle-east-respiratory-syndrome-coronavirus-spike-glycoprotein
#1
Wentao Li, Ruben J G Hulswit, Ivy Widjaja, V Stalin Raj, Ryan McBride, Wenjie Peng, W Widagdo, M Alejandra Tortorici, Brenda van Dieren, Yifei Lang, Jan W M van Lent, James C Paulson, Cornelis A M de Haan, Raoul J de Groot, Frank J M van Kuppeveld, Bart L Haagmans, Berend-Jan Bosch
Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1(A) through S1(D) Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1(B) We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia)...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28903385/dpp-4-enzyme-deficiency-protects-kidney-from-acute-ischemia-reperfusion-injury-role-for-remote-intermittent-bowel-ischemia-reperfusion-preconditioning
#2
Yen-Ta Chen, Christopher Glenn Wallace, Chih-Chao Yang, Chih-Hung Chen, Kuan-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Han-Tan Chai, Sheng-Ying Chung, Sarah Chua, Fan-Yen Lee, Sheung-Fat Ko, Mel S Lee, Hon-Kan Yip
We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4(D)) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4(D)) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4(D), (3) KIR-F344 (4) KIR-DPP4(D), (5) DPP4(D)-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4(D) rats 72 h after acute KIR...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902377/-implementation-of-the-national-guidelines-for-the-treatment-of-diabetes-mellitus-type-2-in-secondary-diabetes-centers
#3
Lydia Marahrens, Daniel Röck, Tjalf Ziemssen, Raimar Kern, Focke Ziemssen, Andreas Fritsche
Background The German National Disease Management Guideline (NVL) on treatment of Type 2 Diabetes recommends lowering of blood glucose in four therapy steps. There is little evidence, how NVL is implemented for the individual patients. Methods 810 patients in secondary diabetes centers were examined within the DiabCheck(OCTplus) trial. Data about the patient's health status (electronic medical record) were classified according to the NVL treatment steps. The degree of implementation was assessed for every person with diabetes type 2 (NCT02 311 504)...
September 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28900535/the-effects-of-aerobic-exercises-and-25-oh-d-supplementation-on-glp1-and-dpp4-level-in-type-ii-diabetic-patients
#4
Naser Rahimi, Mohammad Ali Samavati Sharif, Amir Reza Goharian, Ali Heidarian Pour
BACKGROUND: The purpose of this study was to investigate the effects of an 8-week aerobic exercise and supplementation of 25(OH)D3 on GLP1 and DDP4 levels in men with type II diabetes. METHODS: In this semiexperimental research, among 40-60-year-old men with type II diabetes who were referred to the diabetic center of Isabn-E Maryam hospital in Isfahan; of whom, 48 patients were voluntarily accepted and then were randomly divided into 4 groups: aerobic exercise group, aerobic exercise with 25(OH) D supplement group, 25(OH) D supplement group, and the control group...
2017: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/28894474/a-novel-dynamic-model-describing-the-spread-of-the-mers-cov-and-the-expression-of-dipeptidyl-peptidase-4
#5
Siming Tang, Wanbiao Ma, Peifan Bai
The Middle East respiratory syndrome (MERS) coronavirus, a newly identified pathogen, causes severe pneumonia in humans. MERS is caused by a coronavirus known as MERS-CoV, which attacks the respiratory system. The recently defined receptor for MERS-CoV, dipeptidyl peptidase 4 (DPP4), is generally expressed in endothelial and epithelial cells and has been shown to be present on cultured human nonciliated bronchiolar epithelium cells. In this paper, a class of novel four-dimensional dynamic model describing the infection of MERS-CoV is given, and then global stability of the equilibria of the model is discussed...
2017: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/28888840/teneligliptin-prevents-cardiomyocyte-hypertrophy-fibrosis-and-development-of-hypertensive-heart-failure-in-dahl-salt-sensitive-rats
#6
Masayoshi Yamamoto, Tomoko Ishizu, Yoshihiro Seo, Yoshimi Suto, Seika Sai, Dongzhu Xu, Nobuyuki Murakoshi, Taizo Kimura, Yasushi Kawakami, Kazutaka Aonuma
BACKGROUND: We investigated the effects of the DPP4 inhibitor, teneligliptin, on cardiac function and hemodynamics during heart failure in hypertensive model rats. METHODS AND RESULTS: Fifty-five male Dahl salt-sensitive rats were divided into four groups: control group (0.3% NaCl chow, n=13), hypertension (HT) group (8% NaCl chow, n=20), HT-early TNL group (8% NaCl chow and teneligliptin from 6 weeks, n=10), and HT-late TNL group (8% NaCl chow and teneligliptin from 10 weeks, n=12)...
September 6, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28877934/identification-of-senescent-cell-surface-targetable-protein-dpp4
#7
Kyoung Mi Kim, Ji Heon Noh, Monica Bodogai, Jennifer L Martindale, Xiaoling Yang, Fred E Indig, Sandip K Basu, Kei Ohnuma, Chikao Morimoto, Peter F Johnson, Arya Biragyn, Kotb Abdelmohsen, Myriam Gorospe
Senescent cell accumulation in aging tissues is linked to age-associated diseases and declining function, prompting efforts to eliminate them. Mass spectrometry analysis revealed that DPP4 (dipeptidyl peptidase 4) was selectively expressed on the surface of senescent, but not proliferating, human diploid fibroblasts. Importantly, the differential presence of DPP4 allowed flow cytometry-mediated isolation of senescent cells using anti-DPP4 antibodies. Moreover, antibody-dependent cell-mediated cytotoxicity (ADCC) assays revealed that the cell surface DPP4 preferentially sensitized senescent, but not dividing, fibroblasts to cytotoxicity by natural killer cells...
September 6, 2017: Genes & Development
https://www.readbyqxmd.com/read/28855003/a-review-of-candidate-therapies-for-middle-east-respiratory-syndrome-from-a-molecular-perspective
#8
Ali A Rabaan, Shamsah H Alahmed, Ali M Bazzi, Hatem M Alhani
There have been 2040 laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 34.9 %. There is no specific therapy. The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir-ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The development of specific therapies and vaccines is therefore urgently required...
August 31, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28853228/comparison-of-effects-of-anagliptin-and-alogliptin-on-serum-lipid-profile-in-type-2-diabetes-mellitus
#9
Akira Kurozumi, Yosuke Okada, Tadashi Arao, Takuya Kobayashi, Daisaku Masuda, Shizuya Yamashita, Yoshiya Tanaka
AIMS/INTRODUCTION: Anagliptin (ANA) improves dyslipidemia in addition to blood glucose levels. However, there are no comparative studies on the effects of ANA and other dipeptidyl peptidase-4 inhibitors (DPP4-I) on serum lipid profile. We compared the effects of ANA on serum lipid profile with those of alogliptin (ALO) in type 2 diabetes mellitus (T2DM) outpatients. MATERIALS AND METHODS: The study subjects were 87 T2DM patients who had been treated with DPP4-I for 8 weeks or longer and had low-density lipoprotein cholesterol (LDL-C) level of 120 mg/dl or higher...
August 29, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28815047/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#10
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#11
Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28811850/effect-of-sodium-glucose-cotransporter-2-inhibitors-with-low-sglt2-sglt1-selectivity-on-circulating-glucagon-like-peptide-1-levels-in-type-2-diabetes-mellitus
#12
REVIEW
Kohzo Takebayashi, Toshihiko Inukai
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28807052/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#13
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28801475/understanding-the-gap-between-efficacy-in-randomized-controlled-trials-and-effectiveness-in-real-world-use-of-glp-1ra-and-dpp4-therapies-in-patients-with-type-2-diabetes
#14
Ginger S Carls, Edward Tuttle, Ruo-Ding Tan, Johnny Huynh, John Yee, Steven V Edelman, William H Polonsky
OBJECTIVE: This objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications. RESEARCH DESIGN AND METHODS: This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide-1 receptor agonist (GLP-1RA) or dipeptidyl peptidase-4 inhibitor (DPP4) with published findings from randomized controlled trials (RCTs) evaluating these drugs...
August 11, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28799235/dipeptidyl-peptidase-4-serum-activity-and-concentration-are-increased-in-women-with-polycystic-ovary-syndrome
#15
Sindy Blauschmidt, Thomas Greither, Katharina Lampe, Solveig Köller, Petra Kaltwaßer, Hermann M Behre
OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex disease, the aetiology of which is not well understood. Alterations in potential candidate genes involved in the biosynthesis and metabolism of androgens, folliculogenesis and insulin and glucose metabolism have been suggested as possible aetiologies. Dipeptidyl peptidase-4 (DPP4) plays a key role in glucose homoeostasis and, thus, in the regulation of insulin secretion. The aim of our study was to analyse the DPP4 activity and concentrations in the serum of PCOS and non-PCOS patients and, additionally, study the activation of the DPP4 promoter by androgens in vitro...
August 11, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28798686/strong-association-between-plasma-dipeptidyl-peptidase-4-activity-and-impaired-cognitive-function-in-elderly-population-with-normal-glucose-tolerance
#16
Bo Chen, Tianpeng Zheng, Linyuan Qin, Xueping Hu, Xiaoxi Zhang, Yihong Liu, Hongbo Liu, Shenghua Qin, Gang Li, Qinghua Li
Objective: Inflammation, oxidative stress, and decreased glucagon-like peptide-1 (GLP-1) are risk factors for cognitive impairment. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing these risk factors. Hence, we investigated the relationship between plasma DPP4 activity and impaired cognitive function in elderly Chinese population with normal glucose tolerance (NGT). Methods: We performed a cross-sectional study using data from 1229 elderly participants (60 years or older) in Guilin...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28764219/teneligliptin-in-early-diabetic-kidney-disease-an-observation-in-asian-indian-patients-with-type-2-diabetes-mellitus-in-real-life-scenario
#17
Kiran Shah
INTRODUCTION: Teneligliptin is a recently developed Dipeptidyl Peptidase 4 (DPP4) inhibitor. Teneligliptin is suitable for glycaemic control with renal impairment including end stage renal disease. AIM: To assess the efficacy and safety of teneligliptin in Asian Indian patients of Type 2 Diabetes Mellitus (T2DM) with early Diabetic Kidney Disease (DKD). MATERIALS AND METHODS: This was a single centre, retrospective analysis of patients with early DKD, who received teneligliptin 20 mg once daily for 24 weeks...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28759649/the-tetraspanin-cd9-facilitates-mers-coronavirus-entry-by-scaffolding-host-cell-receptors-and-proteases
#18
James T Earnest, Michael P Hantak, Kun Li, Paul B McCray, Stanley Perlman, Tom Gallagher
Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28756774/heart-failure-hospitalization-risk-associated-with-use-of-two-classes-of-oral-antidiabetic-medications-an-observational-real-world-analysis
#19
Santosh Gautam, Abiy Agiro, John Barron, Thomas Power, Harry Weisman, Jeff White
BACKGROUND: Newer oral antidiabetic drug classes are expanding treatment options for type 2 diabetes mellitus (T2DM); however, concerns remain. The objective was to assess relative risk of heart failure hospitalization of sodium-glucose co-transporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM patients. METHODS: This retrospective observational study used a national commercially insured claims database. Adults (>18 years) with T2DM newly starting SGLT2 or DPP4 medication between April 2013 and December 2014 were included...
July 31, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28750074/dpp4-gene-variation-affects-glp-1-secretion-insulin-secretion-and-glucose-tolerance-in-humans-with-high-body-adiposity
#20
Anja Böhm, Robert Wagner, Fausto Machicao, Jens Juul Holst, Baptist Gallwitz, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger
OBJECTIVE: Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide, collectively termed incretins. DPP-4 inhibitors entered clinical practice as approved therapeutics for type-2 diabetes in 2006. However, inter-individual variance in the responsiveness to DPP-4 inhibitors was reported. Thus, we asked whether genetic variation in the DPP4 gene affects incretin levels, insulin secretion, and glucose tolerance in participants of the TÜbingen Family study for type-2 diabetes (TÜF)...
2017: PloS One
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