keyword
https://read.qxmd.com/read/38625918/contribution-of-amino-acids-in-the-active-site-of-dipeptidyl-peptidase-4-to-the-catalytic-action-of-the-enzyme
#1
JOURNAL ARTICLE
Kathrin Gnoth, Joachim Wolfgang Bär, Fred Rosche, Jens-Ulrich Rahfeld, Hans-Ulrich Demuth
Dipeptidyl peptidase 4 (DP4)/CD26 regulates the biological function of various peptide hormones by releasing dipeptides from their N-terminus. The enzyme is a prominent target for the treatment of type-2 diabetes and various DP4 inhibitors have been developed in recent years, but their efficacy and side effects are still an issue. Many available crystal structures of the enzyme give a static picture about enzyme-ligand interactions, but the influence of amino acids in the active centre on binding and single catalysis steps can only be judged by mutagenesis studies...
2024: PloS One
https://read.qxmd.com/read/38561106/nicotinamide-promotes-the-differentiation-of-functional-corneal-endothelial-cells-from-human-embryonic-stem-cells
#2
JOURNAL ARTICLE
Dulei Zou, Ting Wang, Wenjing Li, Xin Wang, Bochao Ma, Xiangyue Hu, Qingjun Zhou, Zongyi Li, Weiyun Shi, Haoyun Duan
Corneal transplantation represents the primary therapeutic approach for managing corneal endothelial dysfunction, but corneal donors remain scarce. Anterior chamber cell injection emerges as a highly promising alternative strategy for corneal transplantation, with pluripotent stem cells (PSC) demonstrating considerable potential as an optimal cell source. Nevertheless, only a few studies have explored the differentiation of functional corneal endothelial-like cells originating from PSC. In this investigation, a chemical-defined protocol was successfully developed for the differentiation of functional corneal endothelial-like cells derived from human embryonic stem cells (hESC)...
March 30, 2024: Experimental Eye Research
https://read.qxmd.com/read/38506255/molecular-characterization-of-%C3%AE-and-%C3%AE-thalassemia-among-children-less-than-18%C3%A2-years-old-in-guizhou-china
#3
JOURNAL ARTICLE
Yan Li, Jiao Jin, Yuanyuan Tuo, Pei Huang, Jing Huang, Honglan Yang, Zhixu He
BACKGROUND: Thalassemia is an inherited hemolytic disease, the complications and sequelae of which have posed a huge impact on both patients and society. But limited studies have investigated the molecular characterization of α- and β-thalassemia in children from Guizhou, China. METHODS: Between January 2019 and December 2022, a total of 3301 children, aged 6 months to 18 years, suspected of having thalassemia underwent molecular analysis. RESULTS: Out of the total sample, 824 (25%) children were found to carry thalassemia mutations...
March 20, 2024: Journal of Clinical Laboratory Analysis
https://read.qxmd.com/read/38505912/a-systems-biology-approach-unveils-a-critical-role-of-dpp4-in-upper-gastrointestinal-cancer-patient-outcomes
#4
JOURNAL ARTICLE
Sudhir Kotnala, Anupam Dhasmana, Swati Dhasmana, Shafiul Haque, Murali M Yallapu, Manish K Tripathi, Meena Jaggi, Subhash C Chauhan
Gastrointestinal (GI) cancers comprise of cancers that affect the digestive system and its accessory organs. The late detection and poor prognosis of GI cancer emphasizes the importance of identifying reliable and precise biomarkers for early diagnosis and prediction of prognosis. The membrane-bound glycoprotein dipeptidyl-peptidase 4 (DPP4), also known as CD26, is ubiquitously expressed and has a wide spectrum of biological roles. The role of DPP4/CD26 in tumor progression in different types of cancers remains elusive...
2024: Journal of Environmental Pathology, Toxicology and Oncology
https://read.qxmd.com/read/38488824/pharmacotherapeutic-advances-for-chronic-myelogenous-leukemia-beyond-tyrosine-kinase-inhibitors
#5
REVIEW
Alessandro Costa, Emilia Scalzulli, Ida Carmosino, Claudia Ielo, Maria Laura Bisegna, Maurizio Martelli, Massimo Breccia
INTRODUCTION: Despite the notable success of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML), a subset of patients experiences resistance, or relapse after discontinuation. This challenge is attributed to the Ph+ leukemia stem cells (LSCs) pool not fully involved in the inhibition process due to the current therapeutic approach. AREAS COVERED: Current pharmacological advancements in CML therapy focus on targeting LSCs, intervening in self-renewal pathways, and exploiting biological vulnerabilities...
March 15, 2024: Expert Opinion on Pharmacotherapy
https://read.qxmd.com/read/38469626/functional-roles-of-cd26-dpp4-in-lipopolysaccharide-induced-lung-injury
#6
JOURNAL ARTICLE
Shun Sato, Takeshi Kawasaki, Ryo Hatano, Yu Koyanagi, Yukiko Takahashi, Kei Ohnuma, Chikao Morimoto, Steven M Dudek, Koichiro Tatsumi, Takuji Suzuki
Acute respiratory distress syndrome (ARDS) is characterized by dysregulated inflammation and increased permeability of lung microvascular cells. CD26/Dipeptidyl peptidase-4 (DPP4) is a type II membrane protein that is expressed in several cell types and mediates multiple pleiotropic effects. We previously reported that DPP4 inhibition by sitagliptin attenuates lipopolysaccharide (LPS)-induced lung injury in mice. The current study characterized the functional role of CD26/DPP4 expression in LPS-induced lung injury in mice, isolated alveolar macrophages, and cultured lung endothelial cells...
March 12, 2024: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/38284882/hdac-inhibition-induces-cd26-expression-on-myeloma-cells-via-the-c-myc-sp1-mediated-promoter-activation
#7
JOURNAL ARTICLE
Hiroko Nishida, Reiko Suzuki, Kiyora Nakajima, Mutsumi Hayashi, Chikao Morimoto, Taketo Yamada
CD26 is ubiquitously and intensely expressed in osteoclasts in multiple myeloma (MM) patients, whereas its expression in plasma cells of MM patients is heterogeneous because of its cellular diversity, immune escape and disease progression. Decreased expression levels of CD26 in myeloma cells constitutes one of the mechanisms underlying resistance to humanized anti-CD26 monoclonal antibody (mAb) therapy in MM. In the present study, we show that histone deacetylase inhibition (HDACi) with broad or class-specific inhibitors involves the induction of CD26 expression on CD26neg myeloma cells both transcriptionally and translationally...
January 29, 2024: Cancer Res Commun
https://read.qxmd.com/read/38272241/molecular-insights-on-the-coronavirus-mers-cov-interaction-with-the-cd26-receptor
#8
JOURNAL ARTICLE
Hila Failayev, Assaf Ganoth, Yossi Tsfadia
The Middle East respiratory syndrome (MERS) is a severe respiratory disease with high fatality rates, caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus initiates infection by binding to the CD26 receptor (also known as dipeptidyl peptidase 4 or DPP4) via its spike protein. Although the receptor-binding domain (RBD) of the viral spike protein and the complex between RBD and the extracellular domain of CD26 have been studied using X-ray crystallography, conflicting studies exist regarding the importance of certain amino acids outside the resolved RBD-CD26 complex interaction interface...
January 23, 2024: Virus Research
https://read.qxmd.com/read/38255821/functional-roles-of-cd26-dpp4-in-bleomycin-induced-pulmonary-hypertension-associated-with-interstitial-lung-disease
#9
JOURNAL ARTICLE
Tadasu Okaya, Takeshi Kawasaki, Shun Sato, Yu Koyanagi, Koichiro Tatsumi, Ryo Hatano, Kei Ohnuma, Chikao Morimoto, Yoshitoshi Kasuya, Yoshinori Hasegawa, Osamu Ohara, Takuji Suzuki
Pulmonary hypertension (PH) with interstitial lung diseases (ILDs) often causes intractable conditions. CD26/Dipeptidyl peptidase-4 (DPP4) is expressed in lung constituent cells and may be related to the pathogenesis of various respiratory diseases. We aimed to clarify the functional roles of CD26/DPP4 in PH-ILD, paying particular attention to vascular smooth muscle cells (SMCs). Dpp4 knockout ( Dpp4 KO) and wild type (WT) mice were administered bleomycin (BLM) intraperitoneally to establish a PH-ILD model...
January 6, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38247864/coronavirus-receptor-expression-profiles-in-human-mast-cells-basophils-and-eosinophils
#10
JOURNAL ARTICLE
Lina Degenfeld-Schonburg, Irina Sadovnik, Dubravka Smiljkovic, Barbara Peter, Gabriele Stefanzl, Clemens Gstoettner, Peter Jaksch, Konrad Hoetzenecker, Clemens Aigner, Christine Radtke, Michel Arock, Wolfgang R Sperr, Peter Valent
A major problem in SARS-CoV-2-infected patients is the massive tissue inflammation in certain target organs, including the lungs. Mast cells (MC), basophils (BA), and eosinophils (EO) are key effector cells in inflammatory processes. These cells have recently been implicated in the pathogenesis of SARS-CoV-2 infections. We explored coronavirus receptor (CoV-R) expression profiles in primary human MC, BA, and EO, and in related cell lines (HMC-1, ROSA, MCPV-1, KU812, and EOL-1). As determined using flow cytometry, primary MC, BA, and EO, and their corresponding cell lines, displayed the CoV-R CD13 and CD147...
January 17, 2024: Cells
https://read.qxmd.com/read/38237727/computational-flow-cytometry-accurately-identifies-sezary-cells-based-on-simplified-aberrancy-and-clonality-features
#11
JOURNAL ARTICLE
Jansen N Seheult, Matthew J Weybright, Dragan Jevremovic, Min Shi, Horatiu Olteanu, Pedro Horna
Flow cytometric identification of circulating neoplastic cells (Sezary cells) in patients with mycosis fungoides (MF) and Sezary syndrome (SS) is essential for diagnosis, staging and prognosis. While recent advances have improved the performance of this laboratory assay, the complex immunophenotype of Sezary cells and overlap with reactive T cells demand a high level of analytic expertise. We utilized machine learning to simplify this analysis using only 2 pre-defined Sezary cell-gating plots. We studied 114 samples from 59 patients with SS/MF, and 66 samples from unique patients with inflammatory dermatoses...
January 16, 2024: Journal of Investigative Dermatology
https://read.qxmd.com/read/38094101/novel-pharmacological-treatment-options-of-steroid-refractory-graft-versus-host-disease
#12
REVIEW
Iuliia Kovalenko, Tabinda Saleem, Mitali Shah, Sara Seyedroudbari, Konstantin Golubykh, Rimsha Ali, Taaha Mirza, Babray Laek, Ahsan Wahab, Asmi Chattaraj, Ekaterina Proskuriakova, Chandi Garg, Rafiullah Khan
BACKGROUND: Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids, which are ineffective in 30-50% of cases. Steroid-refractory GVHD (SR-GVHD) confers a poor prognosis, with high mortality rates despite appropriate therapy. While there is no reliable treatment for SR-GVHD, a variety of novel therapeutic options are slowly emerging and have yet to be examined simultaneously. OBJECTIVES: This review evaluates the potential of novel therapeutic options, as well as their efficacy and safety, for the treatment of SR-GVHD...
2023: Advances in Hematology
https://read.qxmd.com/read/38071064/-gene-mutation-types-of-thalassemia-in-chongzuo-childbearing-age-population-of-guangxi-zhuang-autonomous-region-of-china
#13
JOURNAL ARTICLE
Dong-Ming Li, Xiu-Ning Huang, Huan Zhao, Xiang Chen, Wan-Wei Yang, Zhen-Ren Peng, Li-Fang Liang, Bi-Yan Chen, Sheng He
OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65...
December 2023: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://read.qxmd.com/read/38069840/saturated-fatty-acids-stimulate-cytokine-production-in-tanycytes-via-the-pp2ac-dependent-signaling-pathway
#14
JOURNAL ARTICLE
Danyang Liu, Tao Wang, Xingqi Zhao, Juan Chen, Tianqi Yang, Yi Shen, Yu-Dong Zhou
The hypothalamic tanycytes are crucial for free fatty acids (FFAs) detection, storage, and transport within the central nervous system. They have been shown to effectively respond to fluctuations in circulating FFAs, thereby regulating energy homeostasis. However, the precise molecular mechanisms by which tanycytes modulate lipid utilization remain unclear. Here, we report that the catalytic subunit of protein phosphatase 2 A (PP2Ac), a serine/threonine phosphatase, is expressed in tanycytes and its accumulation and activation occur in response to high-fat diet consumption...
December 9, 2023: Journal of Cerebral Blood Flow and Metabolism
https://read.qxmd.com/read/38069152/sitagliptin-induces-tolerogenic-human-dendritic-cells
#15
JOURNAL ARTICLE
Marija Drakul, Sergej Tomić, Marina Bekić, Dušan Mihajlović, Miloš Vasiljević, Sara Rakočević, Jelena Đokić, Nikola Popović, Dejan Bokonjić, Miodrag Čolić
Sitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol)...
November 27, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/38067159/in-doxorubicin-adapted-hodgkin-lymphoma-cells-acquiring-multidrug-resistance-and-improved-immunosuppressive-abilities-doxorubicin-activity-was-enhanced-by-chloroquine-and-gw4869
#16
JOURNAL ARTICLE
Naike Casagrande, Cinzia Borghese, Michele Avanzo, Donatella Aldinucci
Classical Hodgkin lymphoma (cHL) is a highly curable disease (70-80%), even though long-term toxicities, drug resistance, and predicting clinical responses to therapy are major challenges in cHL treatment. To solve these problems, we characterized two cHL cell lines with acquired resistance to doxorubicin, KM-H2dx and HDLM-2dx (HRSdx), generated from KM-H2 and HDLM-2 cells, respectively. HRSdx cells developed cross-resistance to vinblastine, bendamustin, cisplatin, dacarbazine, gemcitabine, brentuximab vedotin (BV), and γ-radiation...
November 29, 2023: Cells
https://read.qxmd.com/read/38060494/identification-of-protein-signatures-for-lung-cancer-subtypes-based-on-bpso-method
#17
JOURNAL ARTICLE
Jihan Wang, Hanping Wang, Jing Xu, Qiying Song, Baozhen Zhou, Jingbo Shangguan, Mengju Xue, Yangyang Wang
The objective of this study was to identify protein biomarkers that can distinguish between LUAD and LUSC, critical for personalized treatment plans. The proteomic profiling data of LUAD and LUSC samples from TCPA database, along with phenotype and survival information from TCGA database were downloaded and preprocessed for analysis. We used BPSO feature selection method and identified 10 candidate protein biomarkers that have better classifying performance, as analyzed by t-SNE and PCA algorithms. To explore the causalities among these proteins and their associations with tumor subtypes, we conducted the PCStable algorithm to construct a regulatory network...
2023: PloS One
https://read.qxmd.com/read/38059603/human-placental-vascular-and-perivascular-cell-heterogeneity-differs-between-first-trimester-and-term-and-in-pregnancies-affected-by-fetal-growth-restriction
#18
JOURNAL ARTICLE
Anna L Boss, Lawrence W Chamley, Anna E S Brooks, Joanna L James
Growth-restricted placentae have a reduced vascular network, impairing exchange of nutrients and oxygen. However, little is known about the differentiation events and cell types that underpin normal/abnormal placental vascular formation and function. Here we used 23-colour flow cytometry to characterise placental vascular/perivascular populations between first trimester and term, and in fetal growth restriction (FGR). First-trimester endothelial cells had an immature phenotype (CD144+/lowCD36-CD146low), while term endothelial cells expressed mature endothelial markers (CD36+CD146+)...
December 6, 2023: Molecular Human Reproduction
https://read.qxmd.com/read/38045173/cxcr2-inhibition-overcomes-ponatinib-intolerance-by-eradicating-chronic-myeloid-leukemic-stem-cells-through-pi3k-akt-mtor-and-dipeptidylpeptidase-%C3%A2-cd26
#19
JOURNAL ARTICLE
Ji-Hea Kim, Ka-Won Kang, Yong Park, Byung Soo Kim
This study explores the therapeutic potential of targeting CXCR2 in patients afflicted with ponatinib-resistant chronic myeloid leukemia (CML). Ponatinib, a third-generation tyrosine kinase inhibitor (TKI), was initially designed for treating patients with CML harboring the T315I mutation. However, resistance or intolerance issues may lead to treatment discontinuation. Additionally, TKIs have exhibited limitations in eradicating quiescent CML stem cells. Our investigation reveals the activation of CXC chemokine receptor 2 (CXCR2) signaling in response to chemotherapeutic stress...
November 2023: Heliyon
https://read.qxmd.com/read/38036004/a-self-assembled-graphene-oxide-adjuvant-induces-both-enhanced-humoral-and-cellular-immune-responses-in-influenza-vaccine
#20
JOURNAL ARTICLE
Shiyi Huang, Yiyang Li, Shuang Zhang, Youming Chen, Wenqiong Su, David J Sanchez, John D H Mai, Xiao Zhi, Hongjun Chen, Xianting Ding
Antiviral vaccine is essential for preventing and controlling virus spreading, along with declining morbidity and mortality. A major challenge in effective vaccination lies in the ability to enhance both the humoral and cellular immune responses by adjuvants. Herein, self-assembled nanoparticles based on graphene oxide quantum dots with components of carnosine, resiquimod and Zn2+ ions, namely ZnGC-R, are designed as a new adjuvant for influenza vaccine. With its high capability for antigen-loading, ZnGC-R enhances antigen utilization, improves DC recruitment, and activates antigen-presenting cells...
November 28, 2023: Journal of Controlled Release
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