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Mladen I Yovchev, Michael Oertel
Liver transplantation is the only therapeutic treatment for patients with end-stage liver diseases. However, donor organ scarcity is the major limitation, and therefore, alternative strategies are urgently needed. The ultimate goal for successful cell-based therapies is the ability of transplanted cells to efficiently engraft and reconstitute injured liver mass. To evaluate the repopulation capacity of transplanted cells, it is essential to identify their specific characteristics, as well as to study the mechanism(s) Through which transplanted donor cells replace tissue mass in hepatic microenvironments, using well-established cell transplantation models...
2017: Methods in Molecular Biology
Chunxiang Ye, Xiuyun Tian, Guanjun Yue, Liang Yan, Xiaoya Guan, Shan Wang, Chunyi Hao
CD26/DPPIV is a glycosylated transmembrane type II protein and has a multitude of biological functions, while its impact on the malignant phenotypes of cancer cells has not been fully understood. This study aimed to investigate the effect of CD26 on growth and metastasis of pancreatic cancer cells in vitro and in vivo. We found in this study that CD26 expression was higher in cell lines that derived from the metastatic sites than those from the primary tumor sites. In specimens of pancreatic cancer patients, CD26 expression was higher in cancerous tissues than in paired normal tissues...
October 7, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jaimini Cegla, Ben Jones, James Howard, Richard Kay, Colin S Creaser, Stephen R Bloom, Tricia Tan
BACKGROUND: One of the main challenges in the measurement of glucagon is the premise that it is unstable in human plasma. Traditionally, protease inhibitors have been used to prevent its degradation, however, their use is controversial. Here we investigated the optimal method of sample collection for glucagon, with measurement by liquid chromatography tandem mass spectrometry (LC-MS/MS) and two commercially available immunoassays. METHODS: Blood from healthy fasting volunteers (n=10) was processed under a variety of pre-analytical condition including collection in EDTA vs lithium heparin tubes and the addition of aprotinin and/or a DPPIV inhibitor...
October 4, 2016: Annals of Clinical Biochemistry
Jelka Gabrilovac, Barbara Čupić, Emilija Zapletal, Ognjen Kraus, Jasminka Jakić-Razumović
BACKGROUND: Dipeptidyl peptidase 9 (DPP9) is a relatively new member of the DPPIV family of prolyl dipeptidases which is ubiquitously expressed. Its role in regulation of immune responses and proliferation of epithelial carcinoma cells was reported. There is no data on possible role of DPP9 expressed in skin epithelial cells (keratinocytes) and in dermal fibroblasts. MATERIALS AND METHODS: Transcriptional and protein expression of DPP9 and DPPIV was examined in fibroblasts and keratinocytes isolated from normal human skin...
September 19, 2016: Immunobiology
Antonio Ceriello, Stefano Genovese, Edoardo Mannucci, Edoardo Gronda
Increased levels of glucagon in type 2 diabetes are well known and, until now, have been considered deleterious. However, glucagon has an important role in the maintenance of both heart and kidney function. Moreover, in the past, glucagon has been therapeutically used for heart failure treatment. The new antidiabetic drugs, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors, are able to decrease and to increase glucagon levels, respectively, while contrasting data have been reported regarding the glucagon like peptide 1 receptors agonists...
2016: Cardiovascular Diabetology
Lesley Baerts, Raf Brouns, Kaat Kehoe, Robert Verkerk, Sebastiaan Engelborghs, Peter Paul De Deyn, Dirk Hendriks, Ingrid De Meester
Dipeptidyl peptidase IV (DPPIV) inhibition may be a promising therapeutic strategy for acute stroke treatment, given its potential to prolong the biological half-life of neuroprotective substrates. A related protease, fibroblast activation protein (FAP), was recently shown to inactivate the same substrates. Therefore, it should also be investigated as a potential target in stroke. The study aimed to investigate whether stroke severity and outcome correlate with DPPIV and FAP activities and their kinetics shortly after acute ischemic stroke...
August 26, 2016: Translational Stroke Research
Ognjen Čulić, Mario D Cordero, Tihana Žanić-Grubišić, Anita Somborac-Bačura, Lara Batičić Pučar, Dijana Detel, Jadranka Varljen, Karmela Barišić
Fibromyalgia (FM) is a chronic pain syndrome with number of symptoms that present challenge in terms of diagnosis and treatment. Patients with FM show abnormal profile of purines in plasma. In this work, we measured serum activities of enzymes involved in purine metabolism, namely total adenosine deaminase (ADE) and its isoforms (ADE1 and ADE2), ecto-ATPase, and 5'-nucleotidase (5'-NT). We also measured activity of dipeptidyl peptidase IV (DPPIV) and prolyl endopeptidase (PEP). Spectrophotometric and fluorometric methods were used for enzyme activity determinations...
October 2016: Clinical Rheumatology
Umadevi V Wesley, James F Hatcher, Emine R Ayvaci, Abby Klemp, Robert J Dempsey
Cerebral ischemia evokes abnormal release of proteases in the brain microenvironment that spatiotemporally impact angio-neurogenesis. Dipeptidyl peptidase IV (DPPIV), a cell surface and secreted protease, has been implicated in extracellular matrix remodeling by regulating cell adhesion, migration, and angiogenesis through modifying the functions of the major chemokine stromal-derived factor, SDF1. To elucidate the possible association of DPPIV in ischemic brain, we examined the expression of DPPIV in the post-stroke rat brain and under in vitro ischemia by oxygen glucose deprivation (OGD)...
August 15, 2016: Molecular Neurobiology
Daniel F Arruda-Junior, Flavia L Martins, Rafael Dariolli, Leonardo Jensen, Ednei L Antonio, Leonardo Dos Santos, Paulo J F Tucci, Adriana C C Girardi
Circulating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF...
2016: Frontiers in Physiology
Qiuyu Gong, Wen Shi, Lihong Li, Xiaofeng Wu, Huimin Ma
Dipeptide peptidase IV (DPPIV) and fibroblast activation protein (FAP) are isoenzymes. Evidence shows that DPPIV is related to antitumor immunity, and FAP may be a drug target in cancer therapy, making it seem that the two enzymes might have a synergistic role during the proliferation of cancer cells. Surprisingly, herein, we find an adverse action of DPPIV and FAP in the proliferation process by analyzing their changes with two tailor-made ultrasensitive fluorescent probes. First, the up-regulation of DPPIV and down-regulation of FAP in cancer cells under the stimulation of genistein are detected...
August 16, 2016: Analytical Chemistry
Milica Grujic, Ivana Z Matic, Marija Djordjic Crnogorac, Ana Damjanovic Velickovic, Branka Kolundzija, Oscar J Cordero, Zorica Juranic, Slavica Prodanovic, Maja Zlatanovic, Dragan Babic, Nemanja Damjanov
BACKGROUND: Dipeptidyl peptidase IV (DPPIV/CD26) plays an important role in T cell activation and immune regulation, however the role of this enzyme in early rheumatoid arthritis (eRA) has not been clearly defined. The aim of this study was to determine the serum activity of DPPIV, its expression on peripheral blood mononuclear cells (PBMC) and to examine possible correlations with disease activity (DAS28) in untreated patients with eRA. METHODS: The study included 50 patients newly diagnosed with RA, who had not received any corticosteroid or disease modifying antirheumatic drugs (DMARD) therapy and whose conventional radiographs of hands and feet showed no structural damage...
January 1, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
Thiago de Almeida Salles, Camila Zogbi, Thais Martins de Lima, Camila de Godoi Carneiro, Alexandre Teles Garcez, Hermes Vieira Barbeiro, Ednei Luiz Antonio, Leonardo Dos Santos, Alexandre da Costa Pereira, Paulo José Ferreira Tucci, Daniele de Paula Faria, Francisco Garcia Soriano, Adriana Castello Costa Girardi
Circulating dipeptidyl peptidase IV (DPPIV) activity correlates with cardiac dysfunction in humans and experimental heart failure (HF) models. Similarly, inflammatory markers are associated with poorer outcomes in HF patients. However, the contributions of DPPIV to inflammation in HF remain elusive. Therefore, this study aimed to investigate whether the cardioprotective effects of DPPIV inhibition after myocardial injury are accompanied by reduced cardiac inflammation, whether circulating DPPIV activity correlates with the levels of systemic inflammatory markers in HF patients, and whether leukocytes and/or splenocytes may be one of the sources of circulating DPPIV in HF...
June 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Anna Gumieniczek
Agents introduced into therapy of type 2 diabetes in the last few years are still the subject of numerous clinical and experimental studies. Although many studies have been completed, we still do not know all aspects of these drugs' action, especially the long-term effects of their use. Most questionable is their impact on the processes of cell proliferation, on the cardiovascular and immune systems, on lipids and uric acid metabolism. A summary of the most important observations on the use of three groups of new drugs - analogs of glucagon-like peptide 1 (GLP-1), inhibitors of dipeptidyl peptidase IV (DPPIV) and inhibitors of sodium glucose cotransporters (SGLT1 and SGLT2) - has been made, based on a review of the literature over the past five years (2010-2014)...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
Benjamaporn Wonganu, Bryan W Berger
Fibroblast activation protein (FAP) is a cell-surface serine protease which promotes invasiveness of certain epithelial cancers and is therefore a potential target for cancer drug development and delivery. Unlike dipeptidyl peptidase IV (DPPIV), FAP exhibits prolyl endopeptidase activity and is active as a homodimer with specificity for type I collagen. The mechanism that regulates FAP homodimerization and its relation to prolyl endopeptidase activity is not completely understood. Here, we investigate key residues in the FAP TM domain that may be significant for FAP homodimerization...
August 2016: Biochimica et Biophysica Acta
Xiao-Yue Chang, Yong Yang, Xiao-Qing Jia, Yuan Wang, Li-Na Peng, Xiao-Hong Ai, Cui-Ying Jiang, Jian-Hua Guo, Ting-Ting Wu
OBJECTIVE: The purpose of this study is to explore the correlation between serum dipeptidyl peptidase IV (DPPIV) and chronic obstructive pulmonary disease (COPD) at its various disease states, analyze its applications in the prediction and diagnosis of COPD and test the possibility of DPPIV as the serologic marker for COPD screening. MATERIALS AND METHODS: Samples from 74 patients (42 cases with acute exacerbation of COPD or acute exacerbation COPD (AECOPD) and 32 cases with stable COPD) and 29 control subjects were collected in this study...
March 2016: American Journal of the Medical Sciences
Aline Beckenkamp, Samuel Davies, Júlia Biz Willig, Andréia Buffon
Dipeptidyl peptidase IV (DPPIV/CD26) is a multifunctional protein with intrinsic peptidase activity that inactivates or degrades some bioactive peptides. It is the main cellular binding protein for ecto-adenosine deaminase and interacts with extracellular matrix proteins, besides participating in different signaling pathways. Due to these multiple functions, DPPIV/CD26 has been shown to be closely related to the tumor process. It has been reported that the progression of certain types of cancer is accompanied by a decrease in DPPIV/CD26 expression, and studies have shown that the malignant phenotype can be reverted when DPPIV/CD26 expression is induced in these cancer cells, characterizing this protein as a tumor suppressor...
June 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
C Klemann, L Wagner, M Stephan, S von Hörsten
CD26/DPP4 (dipeptidyl peptidase 4/DP4/DPPIV) is a surface T cell activation antigen and has been shown to have DPP4 enzymatic activity, cleaving-off amino-terminal dipeptides with either L-proline or L-alanine at the penultimate position. It plays a major role in glucose metabolism by N-terminal truncation and inactivation of the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). In 2006, DPP4 inhibitors have been introduced to clinics and have been demonstrated to efficiently enhance the endogenous insulin secretion via prolongation of the half-life of GLP-1 and GIP in patients...
July 2016: Clinical and Experimental Immunology
María Teresa Julián, Núria Alonso, Roger Colobran, Alex Sánchez, Antoni Miñarro, Irma Pujol-Autonell, Jorge Carrascal, Silvia Rodríguez-Fernández, Rosa María Ampudia, Marta Vives-Pi, Manel Puig-Domingo
The transmembrane glycoprotein CD26 or dipeptidyl peptidase IV (DPPIV) is a multifunctional protein. In immune system, CD26 plays a role in T-cell function and is also involved in thymic maturation and emigration patterns. In preclinical studies, treatment with DPPIV inhibitors reduces insulitis and delays or even reverses the new -onset of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. However, the specific mechanisms involved in these effects remain unknown. The aim of the present study was to investigate how DPPIV inhibition modifies the expression of genes in the thymus of NOD mice by microarray analysis...
May 5, 2016: Molecular and Cellular Endocrinology
Jee Eun Lee, Jung Eun Kim, Mi Hwa Lee, Hye Kyoung Song, Jung Yeon Ghee, Young Sun Kang, Hye Sook Min, Hyun Wook Kim, Jin Joo Cha, Jee Young Han, Sang Youb Han, Dae Ryong Cha
Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls...
May 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Mladen I Yovchev, Joseph Locker, Michael Oertel
BACKGROUND & AIMS: Current research focuses on developing alternative strategies to restore decreased liver mass prior to the onset of end-stage liver disease. Cell engraftment/repopulation requires regeneration in normal liver, but we have shown that severe liver injury stimulates repopulation without partial hepatectomy (PH). We have now investigated whether a less severe injury, secondary biliary fibrosis, would drive engraftment/repopulation of ectopically transplanted mature hepatocytes...
June 2016: Journal of Hepatology
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