Chen WT

References (8)

Title : Factors associated with treatment responses to pioglitazone in patients with steatotic liver disease: A 3-year prospective cohort study - Chang_2024_Diabetes.Obes.Metab__
Author(s) : Chang ML , Tai J , Cheng JS , Chen WT , Yang SS , Chiu CH , Chien RN
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to investigate these issues. METHODS: A 3-year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15-30mg/day) was conducted. Phospholipase domain-containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients. RESULTS: Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6months post-treatment, and 105 (83.3%) patients were responders. Compared with non-responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p=.028). Female sex [odds ratio (OR): 4.514, p=.023] and baseline ALT level (OR: 1.015, p=.046; cut-off level: <=82U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24months post-treatment. The total cholesterol levels decreased within 6months, while increases in high-density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis-4 scores were noted only at 24months post-treatment. The 2-year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non-responders. CONCLUSIONS: Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6months post-treatment, while liver fibrosis improvement was not observed until 24months post-treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation.
ESTHER : Chang_2024_Diabetes.Obes.Metab__
PubMedSearch : Chang_2024_Diabetes.Obes.Metab__
PubMedID: 38685616

Title : Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury - Zhang_2015_Sci.Rep_5_15503
Author(s) : Zhang J , Yong Y , Li X , Hu Y , Wang J , Wang YQ , Song W , Chen WT , Xie J , Chen XM , Lv X , Hou LL , Wang K , Zhou J , Wang XR , Song JG
Ref : Sci Rep , 5 :15503 , 2015
Abstract : Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a alpha7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion.
ESTHER : Zhang_2015_Sci.Rep_5_15503
PubMedSearch : Zhang_2015_Sci.Rep_5_15503
PubMedID: 26499847

Title : Enzyme mimics of au\/ag nanoparticles for fluorescent detection of acetylcholine - Wang_2012_Anal.Chem_84_9706
Author(s) : Wang CI , Chen WT , Chang HT
Ref : Analytical Chemistry , 84 :9706 , 2012
Abstract : We have developed a highly sensitive and selective fluorescent assay for the detection of acetylcholine (ACh) based on enzyme mimics of Au/Ag nanoparticles (NPs). These NPs were prepared via a one-step solution phase reaction between 13 nm Au NPs and Ag(+) ions in the presence of stabilizing agents such as adenosine triphosphate (ATP) and polyethylene glycol (PEG). Our sensing strategy involves reacting ACh with acetylcholinesterase (AChE) to form choline that is in turn oxidized by choline oxidase (ChOx) to produce betaine and H(2)O(2), which reacts with Amplex UltraRed (AUR) in the presence of bimetallic NPs catalyst to form a fluorescent product. The fluorescence intensity (excitation/emission wavelengths of 540/592 nm) is proportional to the concentration of ACh over a range of 1-100 nM (R(2) = 0.998), with a limit of detection of 0.21 nM (signal/noise = 3). When compared with Au NPs and horseradish peroxidase, the Au/Ag NPs provide 150- and 115-fold higher catalytic activity toward the H(2)O(2)-mediated AUR reaction. The practicality of the assay has been validated by determining the concentrations of ACh in plasma and blood samples, with results of 2.69 +/- 0.84 nM (n = 5) and 6.75 +/- 1.42 nM (n = 5), respectively. Thus, the present assay holds great potential for the analysis of ACh in biological samples.
ESTHER : Wang_2012_Anal.Chem_84_9706
PubMedSearch : Wang_2012_Anal.Chem_84_9706
PubMedID: 23101755

Title : Seprase, dipeptidyl peptidase IV and urokinase-type plasminogen activator expression in dysplasia and invasive squamous cell carcinoma of the esophagus. A study of 229 cases from Anyang Tumor Hospital, Henan Province, China - Goscinski_2008_Oncology_75_49
Author(s) : Goscinski MA , Suo ZH , Nesland JM , Chen WT , Zakrzewska M , Wang J , Zhang S , Florenes VA , Giercksky KE
Ref : Oncology , 75 :49 , 2008
Abstract : OBJECTIVE: Seprase, dipeptidyl peptidase IV (DPPIV) and urokinase-type plasminogen activator (uPA) play a crucial role in the degradation of the extracellular matrix and in the progression of various human tumors. However, their pathophysiologic significance in esophageal carcinoma has not yet been fully elucidated.
METHODS: The expression of seprase, DPPIV and uPA in esophageal dysplasia, squamous cell carcinoma (SCC) and normal epithelium was examined by immunohistochemistry.
RESULTS: Seprase, DPPIV and uPA immunoreactivity was found in dysplastic and cancer cells as well as in stromal cells adjacent to dysplasia and cancer sites, but not in normal epithelium. We found a significant association between uPA expression and sex, tumor size and histological classification in carcinomas. High expression of DPPIV in cancer cells correlated with longer survival of the patients. No significant associations between seprase and clinicopathological features either in dysplasia or in carcinomas were found. Finally, we demonstrated higher levels of seprase, DPPIV and uPA in SCC cell lines than in normal esophageal epithelial cell lines.
CONCLUSIONS: Our results showed that seprase, DPPIV and uPA are expressed in both premalignant and malignant forms of SCC, but are lacking in normal esophageal epithelia, suggesting that they are involved in SCC neoplastic progression.
ESTHER : Goscinski_2008_Oncology_75_49
PubMedSearch : Goscinski_2008_Oncology_75_49
PubMedID: 18787344

Title : The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices - Ghersi_2006_Cancer.Res_66_4652
Author(s) : Ghersi G , Zhao Q , Salamone M , Yeh Y , Zucker S , Chen WT
Ref : Cancer Research , 66 :4652 , 2006
Abstract : Dipeptidyl peptidase IV (DPP4/CD26) and seprase/fibroblast activation protein alpha are homologous type II transmembrane, homodimeric glycoproteins that exhibit unique prolyl peptidase activities. Human DPP4 is ubiquitously expressed in epithelial and endothelial cells and serves multiple functions in cleaving the penultimate positioned prolyl bonds at the NH(2) terminus of a variety of physiologically important peptides in the circulation. Recent studies showed a linkage between DPP4 and down-regulation of certain chemokines and mitogenic growth factors, and degradation of denatured collagens (gelatin), suggesting a role of DPP4 in the cell invasive phenotype. Here, we found the existence of a novel protease complex consisting of DPP4 and seprase in human endothelial cells that were activated to migrate and invade in the extracellular matrix in vitro. DPP4 and seprase were coexpressed with the three major protease systems (matrix metalloproteinase, plasminogen activator, and type II transmembrane serine protease) at the cell surface and organize as a complex at invadopodia-like protrusions. Both proteases were colocalized at the endothelial cells of capillaries, but not large blood vessels, in invasive breast ductal carcinoma in vivo. Importantly, monoclonal antibodies against the gelatin-binding domain of DPP4 blocked the local gelatin degradation by endothelial cells in the presence of the major metallo- and serine protease systems that modified pericellular collagenous matrices and subsequent cell migration and invasion. Thus, we have identified a novel mechanism involving the DPP4 gelatin-binding domain of the DPP4-seprase complex that facilitates the local degradation of the extracellular matrix and the invasion of the endothelial cells into collagenous matrices.
ESTHER : Ghersi_2006_Cancer.Res_66_4652
PubMedSearch : Ghersi_2006_Cancer.Res_66_4652
PubMedID: 16651416

Title : Identification of an alternatively spliced seprase mRNA that encodes a novel intracellular isoform - Goldstein_2000_J.Biol.Chem_275_2554
Author(s) : Goldstein LA , Chen WT
Ref : Journal of Biological Chemistry , 275 :2554 , 2000
Abstract : Seprase is a homodimeric 170-kDa integral membrane gelatinase that is related to the ectoenzyme dipeptidyl peptidase IV. We have identified an alternatively spliced seprase messenger from the human melanoma cell line LOX that encodes a novel truncated isoform, seprase-s. The splice variant mRNA is generated by an out-of-frame deletion of a 1223-base pair exonic region that encodes part of the cytoplasmic tail, transmembrane, and the membrane proximal-central regions of the extracellular domain (Val(5) through Ser(412)) of the seprase 97-kDa subunit (seprase-l). The seprase-s mRNA has an elongated 5' leader (548 nucleotides) that harbors at least two upstream open reading frames that inhibit seprase-s expression from a downstream major open reading frame. Deletion mutagenesis of the wild type splice variant cDNA confirms that initiation of the seprase-s coding sequence begins with an ATG codon that corresponds to Met(522) of seprase-l. The seprase-s open reading frame encodes a 239-amino acid polypeptide with an M(r) approximately 27,000 that precisely overlaps the carboxyl-terminal catalytic region of seprase-l.
ESTHER : Goldstein_2000_J.Biol.Chem_275_2554
PubMedSearch : Goldstein_2000_J.Biol.Chem_275_2554
PubMedID: 10644713
Gene_locus related to this paper: human-FAP

Title : Identification of the 170-kDa melanoma membrane-bound gelatinase (seprase) as a serine integral membrane protease - Pineiro-Sanchez_1997_J.Biol.Chem_272_7595
Author(s) : Pineiro-Sanchez ML , Goldstein LA , Dodt J , Howard L , Yeh Y , Tran H , Argraves WS , Chen WT
Ref : Journal of Biological Chemistry , 272 :7595 , 1997
Abstract : The 170-kDa membrane-bound gelatinase, seprase, is a cell surface protease, the expression of which correlates with the invasive phenotype of human melanoma and carcinoma cells. We have isolated seprase from cell membranes and shed vesicles of LOX human melanoma cells. The active enzyme is a dimer of N-glycosylated 97-kDa subunits. Sequence analysis of three internal proteolytic fragments of the 97-kDa polypeptide revealed up to 87.5% identity to the 95-kDa fibroblast activation protein alpha (FAPalpha), the function of which is unknown. Thus, we used reverse transcription-polymerase chain reaction to generate a 2.4-kilobase cDNA from LOX mRNA with FAPalpha primers. COS-7 cells transfected with this cDNA expressed a 170-kDa gelatinase that is recognized by monoclonal antibodies directed against seprase. Sequence analysis also showed similarities to the 110-kDa subunit of dipeptidyl peptidase IV (DPPIV). Like DPPIV, the gelatinase activity of seprase was completely blocked by serine-protease inhibitors, including diisopropyl fluorophosphate. Seprase could be affinity-labeled by [3H]diisopropyl fluorophosphate, but the proteolytically inactive 97-kDa subunit could not, confirming the existence of a serine protease active site on the dimeric form. Proteolytic activity is lost upon dissociation into its 97-kDa subunit following treatment with acid, heat, or cysteine and histidine-modifying agents. We conclude that seprase, FAPalpha, and DPPIV are related serine integral membrane proteases and that seprase is similar to DPPIV, the proteolytic activities of which are dependent upon subunit association.
ESTHER : Pineiro-Sanchez_1997_J.Biol.Chem_272_7595
PubMedSearch : Pineiro-Sanchez_1997_J.Biol.Chem_272_7595
PubMedID: 9065413
Gene_locus related to this paper: human-FAP

Title : Molecular cloning of seprase: a serine integral membrane protease from human melanoma - Goldstein_1997_Biochim.Biophys.Acta_1361_11
Author(s) : Goldstein LA , Ghersi G , Pineiro-Sanchez ML , Salamone M , Yeh Y , Flessate D , Chen WT
Ref : Biochimica & Biophysica Acta , 1361 :11 , 1997
Abstract : Seprase is a homodimeric 170 kDa integral membrane gelatinase whose expression correlates with the invasiveness of the human melanoma cell line LOX. Here, we report the molecular cloning of a cDNA that encodes the 97 kDa subunit of seprase. Its deduced amino acid sequence predicts a type II integral membrane protein with a cytoplasmic tail of 6 amino acids, followed by a transmembrane domain of 20 amino acids and an extracellular domain of 734 amino acids. The carboxyl terminus contains a putative catalytic region (approximately 200 amino acids) which is homologous (68% identity) to that of the nonclassical serine protease dipeptidyl peptidase IV (DPPIV). The conserved serine protease motif G-X-S-X-G is present as G-W-S-Y-G. However, sequence analysis of seprase cDNA from LOX and other cell lines strongly suggests that seprase and human fibroblast activation protein alpha (FAP alpha) are products of the same gene. We propose that seprase/FAP alpha and DPPIV represent a new subfamily of serine integral membrane proteases (SIMP).
ESTHER : Goldstein_1997_Biochim.Biophys.Acta_1361_11
PubMedSearch : Goldstein_1997_Biochim.Biophys.Acta_1361_11
PubMedID: 9247085