Homo sapiens
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PROVIDER: PRJNA309835 | ENA |
REPOSITORIES: ENA
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Project description:Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs, especially in older people. Although these drugs are usually considered safe, recent evidence suggests that high dose and/or long term use of PPIs may have several detrimental effects, including increased risk of adverse cardiovascular events. The impact of PPI in the aging host environment still need to be characterized. Aged tissues, including vascular tissues, accumulate senescent cells that can communicate with their environment by secreting a myriad of cytokines and growth factors. Human coronary artery endothelial cells (HCAECs) provide an excellent model system to study â??in vitroâ?? most aspects of cardiovascular function and disease related to cellular senescence. The purpose of this study is thus to investigate the in vitro effects of two well-known PPIs (Omeprazole and Lansoprazole) on endothelial gene expression in senescent e non-senescent HCAECs. We used a cDNA microarray method to compare gene expression profiles of young and senescent HCAECs treated with omeprazole and lansoprazole. Young cells were cultured in medium supplemented with vehicle (CTRL) or 100μM PPIs (Omeprazole or Lansoprazole) and grown for subsequent passages until they evidenced senescence-associated phenotypes. Total mRNA was extracted and gene expression profiles were analyzed in senescent endothelial cells (P12) compared to the non-senescent cells (P6) in both untreated (CTRL) and PPI-treated groups by cDNA microarray. All experiments were performed in triplicate for each treatment group.
2017-04-18 | E-GEOD-77239 | biostudies-arrayexpress
Project description:Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs, especially in older people. Although these drugs are usually considered safe, recent evidence suggests that high dose and/or long term use of PPIs may have several detrimental effects, including increased risk of adverse cardiovascular events. The impact of PPI in the aging host environment still need to be characterized. Aged tissues, including vascular tissues, accumulate senescent cells that can communicate with their environment by secreting a myriad of cytokines and growth factors. Human coronary artery endothelial cells (HCAECs) provide an excellent model system to study “in vitro” most aspects of cardiovascular function and disease related to cellular senescence. The purpose of this study is thus to investigate the in vitro effects of two well-known PPIs (Omeprazole and Lansoprazole) on endothelial gene expression in senescent e non-senescent HCAECs. We used a cDNA microarray method to compare gene expression profiles of young and senescent HCAECs treated with omeprazole and lansoprazole.
2017-04-18 | GSE77239 | GEO
Project description:Recent clinical studies indicated Proton-pump inhibitors (PPIs) but not H2 Receptor Antagonists were associated with a decreased risk of esophageal adenocarcinoma. We’d like to clarify whether PPIs interfere with Barrett’s esophagus(BE) pathogenesis during BE treatment and explore the novel roles of omeprazole beyond acid suppression. RNA deep-sequencing was conducted in BE organoids exposed to periodic bile acids(400µM, pH 5.5) stimulation with or without omeprazole（40µM）treatment. A total of 129 long non-coding RNAs, 20 microRNAs, and 285 mRNAs were significantly regulated. Then, bioinformatics tools and databases were employed to explore the potential functions and relationships of these RNAs. Our data showed that the most significantly involved pathways modulated by omeprazole were Phenylalanine metabolism and Glycosaminoglycan biosynthesis - keratan sulfate. In addition, the miRNA-mRNA-lncRNA network regulated by omeprazole was constructed. We have demonstrated some novel acid-independent mechanisms of omeprazole that might yield valuable insight into clinical management of BE, irrespective of acid reflux symptoms.
2021-10-23 | GSE121788 | GEO
Project description:Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder triggered by specific food antigens, characterized by eosinophil-rich multicellular inflammation and structural changes in the epithelium. Treatment options for EoE include dietary therapy, pharmacological therapy, or a combination of both, chosen based on the patient's preference and clinical progression. Pharmacological options include proton pump inhibitors (PPIs), corticosteroids, and biologic therapy. Although PPI therapy is used for EoE management, its underlying mechanism of action remains unclear. To investigate the effects of omeprazole, an orally bioavailable PPI commonly used for EoE therapy, on the dynamics of esophageal epithelial barrier function and inflammation, we employed air-liquid interface (ALI) culture. We examined how omeprazole affects gene expression changes caused by IL-13 treatment. ALI cultures were treated with 100 ng/ml of IL-13 and/or 50 µM of acid-activated omeprazole for 96 hours, and bulk RNA sequencing was performed to analyze the epithelial-specific transcriptomes of IL-13 and/or omeprazole-treated ALI. Our findings suggest potential gene interactions where omeprazole may mitigate transcriptional changes induced by IL-13, indicating that omeprazole may attenuate IL-13 mediated epithelial dysfunction relevant to EoE pathophysiology by modulating pathways associated with inflammation, tissue repair, and cell-cell communication.
2024-09-13 | GSE273039 | GEO
Project description:Expression data from young and senescent melanocytes
| PRJNA327413 | ENA
Project description:Data expression of young and senescent human mesenchymal stem cells (hMSC).
| PRJNA243643 | ENA
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Background & Aims: Because the pathophysiology of GERD is not fully understood, presently used drug target only one or more of the known underlying mechanisms but are not fully effective in all patients. 1Identifying novel central targets may pave the way to develop more effective agents. Methods: A surgical model of sub-chronic reflux esophagitis was developed. Wistar rats were pretreated for 7days with omeprazole (standard proton pump inhibitor) or STW5 (herbal preparation of established efficacy in gastro-intestinal disorders). Treatment was continued for 10days after surgery, rats were sacrificed and esophagi excised. Histological, proteomic and transcriptomic methods were applied to identify reflux induced changes and treatment responses. Results: Protection against reflux induced inflammation was achieved by both test drugs. Both reduced macroscopic and microscopic lesions of the esophagi as well as most measured pro-inflammatory cytokines without significantly affecting NF-kB activity. Proteomic and transcriptomic analysis identified CINC1-3, MIP-1/3α, MIG, RANTES and IL-1β as highly relevant mediators in GERD. Other highly regulated genes were those of IL-6, CCL3, CCL7 and LOX-1. Many affected cyto-/chemokines were involved in the TREM-1 signaling pathway. The fatty acid receptor GPR84 was highly up-regulated in esophagitis but down-regulated by both drugs. This was confirmed by Western blot and immune-histochemical staining, showing for the first time expression of this receptor in esophageal tissue and its possible involvement in GERD. Conclusion: STW5 and omeprazole target a broad spectrum of molecules involved in immunological and inflammatory processes, of which IL-8 (CINC1-3), TREM-1 pathway and GPR84 are proposed to be most promising novel targets for the treatment of GERD. Refluxesophagitis was surgically induced. Wistar rats were pretreated for 7 days with omeprazole or STW5. Treatment was continued for 10days after surgery, rats were sacrificed and esophagi exiced. The study had 5 groups. Group 1: sham operated, Group 2: esophagitis group, untreated, Group3: esophagitis treated with STW5 0.5ml/kg. Group 4: esophagitis treated with STW5 2ml/kg. Group 5: esophagitis treated with Omeprazole (30mg/kg). 4 microarrays from esophageal tissue and blood from 4 animals of each group were performed.
2015-12-16 | E-GEOD-63401 | biostudies-arrayexpress