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Hypoxia-inducible factor-1αin myocardial infarction

World Journal of Cardiology 2024年第4期16卷 181-185页

作者： IvanaŠkrlec Sergey N Kolomeichuk Faculty of Dental Medicine and Health Josip Juraj Strossmayer University of OsijekOsijek 31000Croatia Institute of Biology Karelia Research Center of Russian Academy of SciencesPetrozavodsk 185910Russia Laboratory for Genomics Proteomicsand MetabolomicsResearch Institute of Biomedicine and Biomedical TechnologiesTyumen State Medical UniversityTyumen 625023Russia

Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic *** importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac *** oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and ***,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1α*** expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial *** variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular *** addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in *** editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to *** the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.

关键词： Cardiovascular pathologies Circadian genes Hypoxia-inducible factor 1 Hypoxia Gene-gene interaction

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Inhibition of xanthine oxidase alleviated pancreatic necrosis via HIF-1α-regulated LDHA and NLRP3 signaling pathway in acute pancreatitis

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3591-3604页

作者： Juan Rong Chenxia Han Yan Huang Yiqin Wang Qi Qiu Manjiangcuo Wang Shisheng Wang Rui Wang Juqin Yang Xia Li Chenggong Hu Zhiyao Chen Lihui Deng Wei Huang Qing Xi Dan Du West China Center of Excellence for Pancreatitis Institute of Integrated Traditional Chinese and Western MedicineWest China Hospital/West China Medical SchoolSichuan UniversityChengdu 610041China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Advanced Mass Spectrometry Center Research Core FacilityFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610213China proteomics-metabolomics Platform Research Core FacilityInstitutes for Systems GeneticsWest China HospitalSichuan UniversityChengdu 610093China Biobank West China HospitalSichuan UniversityChengdu 610093China West China School of Nursing Sichuan UniversityChengdu 610041China Department of Critical Care Medicine West China HospitalSichuan UniversityChengdu 610041China

Acute pancreatitis(AP)is a potentially fatal condition with no targeted treatment *** inhibiting xanthine oxidase(XO)in the treatment of AP has been studied in several experimental models and clinical trials,whether XO is a target of AP and what its the main mechanism of action is remains ***,we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger *** first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP *** also found that allopurinol and febuxostat,as purine-like and non-purine XO inhibitors,respectively,exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time ***,we observed that conditional Xdh overexpression aggravated pancreatic necrosis and *** mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha(HIF-1α)-regulated lactate dehydrogenase A(LDHA)and NOD-like receptor family pyrin domain containing 3(NLRP3)signaling pathways and reduced the enrichment of^(13)C_(6)-glucose to^(13)C_(3)-***,we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels,while pancreatic XO and urate were also increased in severe AP *** results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.

关键词： Xanthine oxidase inhibitor Multi-omics HIF-1a Necrotizing acute pancreatitis Lactate Therapeutic target NLRP3 Metabolic flux

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CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer

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Genes & Diseases 2024年第4期11卷 381-399页

作者： Ming Shao Qingfei Pan Haiyan Tan Jing Wu Ha Won Lee Andrew D.Huber William C.Wright Ji-Hoon Cho Jiyang Yu Junmin Peng Taosheng Chen Department of Chemical Biology and Therapeutics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Computational Biology St.Jude Children's Research HospitalMemphisTN 38105USA Center for proteomics and metabolomics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Structural Biology St.Jude Children's Research HospitalMemphisTN 38105USA Department of Developmental Neurobiology St.Jude Children's Research HospitalMemphisTN 38105USA

CYP3A5 is a cytochrome P450(CYP)enzyme that metabolizes drugs and contributes to drug resistance in ***,it remains unclear whether CYP3A5 directly influences cancer *** this report,we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal ***-omics analysis showed that CYP3A5 knockdown re-sults in a decrease in various glucose-related metabolites through its effect on glucose trans-port.A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP,a negative regulator of ***,CYP3A5-generated reactive oxygen species were proved to be responsible for atten-uating the AKT-4EBP1-TXNIP signaling ***3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic *** together,our results,for the first time,reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

关键词： Cell migration CYP3A5 Glucose metabolism GLUT1 Pancreatic cancer TXNIP

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Voluntary wheel running ameliorated the deleterious effects of high-fat diet on glucose metabolism,gut microbiota and microbial-associated metabolites

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Food Science and Human Wellness 2024年第3期13卷 1672-1684页

作者： Ling Zhang Wenyu Zou Yongyan Hu Honghua Wu Ying Gao Junqing Zhang Jia Zheng Department of Endocrinology Peking University First HospitalBeijing 100034China Laboratory Animal facility Peking University First HospitalBeijing 100034China

Exercise training is critical for the early prevention and treatment of obesity and diabetes ***,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and *** showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia *** profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis *** conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose *** further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.

关键词： High-fat diet Voluntary wheel running Gut microbiota metabolomics Glucose metabolism

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Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev Chi Chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical proteomics Core facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the *** is a major pathophysiology in *** previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain *** this study,we demonstrated that oral ProEGCG can be effective in preventing and treating ***,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,*** simulation and BioLayer interferometry were used to confirm their binding *** results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

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Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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Neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical Neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

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A novel homozygous missense variant in ARSK causes MPS X,a new subtype of mucopolysaccharidosis

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Genes & Diseases 2024年第3期11卷 87-90页

作者： Miao Sun Cornelia K.Kaminsky Philip Deppe Mai-Brittllse Frederic M.Vaz Barbara Plecko Torben Lubke Linda M.Randolph Division of Genomic Medicine Department of Pathology and Laboratory MedicineChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Radiology Children's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Chemistry BiochemistryBielefeld UniversityBielefeld 33615Germany Amsterdam UMC Location University of Amsterdam Department of Clinical Chemistry and PediatricsLaboratory Genetic Metabolic DiseasesEmma Children's HospitalMeibergdreef 9Amsterdam 1100 DEthe Netherlands Amsterdam Gastroenterology Endocrinology Metabolism Inborn Errors of MetabolismAmsterdam 1105 BKthe Netherlands Core facility metabolomics Amsterdam UMC Location University of AmsterdamAmsterdam 1100DDthe Netherlands Department of Pediatrics Division of General PediatricsMedical Universityof GrazGraz8036Austria Division of Medical Genetics Department of PediatricsChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA

Mucopolysaccharidoses(MPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage of glycosaminoglycans in cells throughout the *** leads to multisystem abnormalities involving bone,connective tissues,brain,blood,spinal cord,skin,and other tissues.

关键词： metabolism doses polys

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Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer

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Protein & Cell 2021年第2期12卷 89-106页

作者： Jing Zhang Peter ten Dijke Manfred Wuhrer Tao Zhang Oncode Institute and Cell Chemical Biology Leiden University Medical Center2300 RC LeidenThe Netherlands Center for proteomics and metabolomics Leiden University Medical CenterLeidenThe Netherlands

Glycosylation is a common posttranslational modification on membrane-associated and secreted proteins that is of pivotal importance for regulating cell *** glycosylation can lead to uncontrolled cell proliferation,cell-matrix interactions,migration and differentiation,and has been shown to be involved in cancer and other *** epithelial-to-mesenchymal transition is a key step in the metastatic process by which cancer cells gain the ability to invade tissues and extravasate into the *** cellular transformation process,which is associated by morphological change,loss of epithelial traits and gain of mesenchymal markers,is triggered by the secreted cytokine transforming growth factor-β(TGF-β).TGF-βbioactivity is carefully regulated,and its effects on cells are mediated by its receptors on the cell *** this review,we first provide a brief overview of major types of glycans,namely,N-glycans,O-glycans,glycosphingolipids and glycosaminoglycans that are involved in cancer ***,we summarize studies on how the glycosylation of TGF-βsignaling components regulates TGF-βsecretion,bioavailability and TGF-βreceptor ***,we review glycosylation changes associated with TGF-β-induced epithelial-to-mesenchymal transition in *** and understanding the mechanisms by which glycosylation affects TGF-βsignaling and downstream biological responses will facilitate the identification of glycans as biomarkers and enable novel therapeutic approaches.

关键词： cancer epithelial-to-mesenchymal transition glycosphingolipids N-glycosylation Oglycosylation transforming growth factor-β

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The mRNA Binding Proteome of Proliferating and Differentiated Muscle Cells

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Genomics, proteomics & Bioinformatics 2020年第4期18卷 384-396页

作者： Monika Hiller Miriam Geissler George Janssen Peter van Veelen Annemieke Aartsma-Rus Pietro Spitali Department of Human Genetics Leiden University Medical CenterLeiden 2333 ZCthe Netherlands Center for proteomics and metabolomics Leiden University Medical CenterLeiden 2333 ZCthe Netherlands

Muscle formation is a coordinated process driven by extensive gene expression changes where single cells fuse together to form multinucleated muscle fibers. Newly synthesized m RNAs are then regulated by RNA binding proteins(RBPs), affecting post-transcriptional transcript metabolism. Here, we determined how large-scale gene expression changes affect the catalog of RBPs by studying proliferating and differentiated muscle cells in healthy and dystrophic conditions. Transcriptomic analysis showed that the expression of more than 7000 genes was affected during myogenesis. We identified 769 RBPs, of which 294 were muscle-specific and 49 were uniquely shared with cardiomyocytes. A subset of 32 RBPs(half of which were muscle-specific) was found to be preferentially associated with target mRNAs in either myoblasts(MBs) or myotubes(MTs). A large proportion of catalytic proteins were bound to mRNAs even though they lack classical RNA binding domains. Finally, we showed how the identification of cell-specific RBPs enabled the identification of biomarkers that can separate healthy individuals from dystrophic patients. Our data show how interactome data can shed light on new basic RNA biology as well as provide cell-specific data that can be used for diagnostic purposes.

关键词： RNA binding protein Interactome Duchenne muscular dystrophy proteomics Skeletal muscle

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proteomics analysis of coronary atherosclerotic heart disease with different Traditional Chinese Medicine syndrome types before and after percutaneous coronary intervention

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Journal of Traditional Chinese Medicine 2024年第3期44卷 554-563页

作者： WANG Zhibo LI Ying WANG Daoping MA Bo MIAO Lan REN Junguo LIU Jinghua LIU Jianxun Beijing Key Laboratory of Pharmacology of Chinese Materia Region Institute of Basic Medical SciencesXiyuan HospitalChina Academy of Chinese Medical SciencesNational Clinical Research Center of Cardiovascular Disease of Traditional Chinese MedicineBeijing 100000China the National Key facility for Crop Gene Resources and Genetic Improvement Institute of Crop ScienceChinese Academy of Agricultural ScienceBeijing 100098China Department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

OBJECTIVE: To investigate the underlying protein molecular mechanisms of "Qi stagnation and blood stasis syndrome"(QS) and "Qi deficiency and blood stasis syndrome"(QD), as two subtypes of coronary artery disease(CAD) in Traditional Chinese Medicine(TCM),following percutaneous coronary intervention(PCI).METHODS: In this study, a total of 227 CAD patients with QS and 211 CAD patients with QD were enrolled;all participants underwent PCI. Label-free quantification proteomics were employed to analyze the changes in serum in two subtypes of CAD patients before and 6 months after PCI, aiming to elucidate the intervention mechanism of PCI in treating CAD characterized by two different TCM ***: Biochemical analysis revealed significant changes in tumor necrosis factor-α, high density lipoprotein cholesterol, blood stasis clinical symptoms observation, and Gensini levels in both patient groups post-PCI;Proteomic analysis identified 79 and 95 differentially expressed proteins in the QS and QD patient groups, respectively, compared to their control *** C8 alpha chain, complement factor H,apolipoprotein H, apolipoprotein B, plasminogen,carbonic anhydrase 2, and complement factor Ⅰ were altered in both comparison groups. Furthermore,enrichment analysis demonstrated that cell adhesion and connectivity-related processes underwent changes in QS patients post-PCI, whereas lipid metabolism-related pathways, including the peroxisome proliferator-activated receptor signaling pathway and extracellular matrix receptor interaction, underwent changes in the QD *** protein-protein interaction network analysis further enriched 52 node proteins, including apolipoprotein B,lipoprotein(a), complement C5, apolipoprotein A4,complement C8 alpha chain, complement C8 beta chain,complement C8 gamma chain, apolipoprotein H,apolipoprotein A-Ⅱ, albumin, complement C4-B,apolipoprotein C3, among others. The functional network of these proteins is posited to contribute to

关键词： percutaneous coronary intervention proteomics peptide mapping coronary atherosclerotic heart disease Traditional Chinese Medicine syndrome

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