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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

Soluble epoxide hydrolase:a next-generation drug target for Alzheimer's disease and related dementias

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维普期刊数据库

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Neural Regeneration Research 2025年第9期20卷 2585-2586页

作者： andrew Gregory Chengyun Tang Fan Fan department of Physiology Medical College of GeorgiaAugusta UniversityAugustaGAUSA

Alzheimer's disease(Ad)and Alzheimer's diseaserelated dementias(AdRd)represent a significant public health challenge,with projections indicating a substantial increase in affected individuals due to the aging global *** the World Health Organization,Ad/AdRd has affected more than 55 million individuals worldwide,with an additional 10 million cases diagnosed each year.

关键词： Alzheimer population drug

Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

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Neural Regeneration Research 2025年第3期20卷 813-814页

作者： Joel Gruchot Laura Reiche andrew Chan Robert Hoepner Patrick Küry department of Neurology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University DüsseldorfDüsseldorfGermany department of Neurology InselspitalBern University Hospital and University of BernBernSwitzerland

Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human dNA.

关键词： endogenous inflammation Human

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高速列车的有源调节受电弓

大功率变流技术 1994年第8期 7-12页

作者： d.huber 王渤洪德

根据线性化的受电弓模型和各种不同的接触网影响模型,试验了几种调节受电弓的方案,其目的是分析有源调节受电弓的可行性,结果表明所谓谐振滤波器电路是有效的,特别是平稳的调节参数是实现有源调节的重要观点。

关键词：受电弓接触网模拟试验调节

Biochemical dissection of STAT3 signaling in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3229-3230页

作者： Savina Apolloni Nadia d’Ambrosi department of Biology University of Rome Tor VergataRomeItaly

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons,clinically marked by muscle atrophy and *** the clinical course is highly variable,the average time from the onset of symptoms to the need for respiratory support or death is 3-5 *** is the most prevalent motor neuron disease in adults,occurring at a rate of 2 per 100,000 individuals and affecting 5.4 per 100,000 individuals overall.

关键词： STAT3 dissection sclerosis

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： danko Jeremic Lydia Jiménez-díaz Juan d.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(Ad)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in Ad,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

Challenges in Understanding Genome-Wide dNA Methylation

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Journal of Computer Science & Technology 2010年第1期25卷 26-34页

作者：张伟奇 andrew d. Smith Cold Spring Harbor Laboratory Cold Spring Harbor Bioinformatics division TNLIST and MOE Key Lab of Bioinformatics Tsinghua University department of Biological Sciences University of Southern California

dNA methylation is a chemical modification of the bases in genomes. This modification, most frequently found at CpG dinucleotides in eukaryotes, has been identified as having multiple critical functions in broad and diverse species of animals and plants, while mysteriously appears to be lacking from several other well-studied species. dNA methylation has well known and important roles in genome stability and defense, its pattern change highly correlates with gene regulation. Much evidence has linked abnormal dNA methylation to human diseases. Most prominently, aberrant dNA methylation is a common feature of cancer genomes. Elucidating the precise functions of dNA methylation therefore has great biomedical significance. Here we provide an update on large-scale experimental technologies for detecting dNA methylation on a genomic scale. We also discuss new prospect and challenges that computational biologist will face when analyzing dNA methylation data.

关键词： dNA methylation epigenome computational epigenomics

Remaking a connection:molecular players involved in post-injury synapse formation

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Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： diogo Tomé Ramiro d.Almeida iBiMEd-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-Center for Neuroscience and Cell Biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

dihydropyrimidine dehydrogenase polymorphisms in patients with gastrointestinal malignancies and their impact on fluoropyrimidine tolerability: Experience from a single Italian institution

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 101-109页

作者： Mariarosaria d'Amato Gennaro Iengo Nicola Massa Chiara Carlomagno department of Oncology Ospedale San Rocco ASL CasertaSessa Aurunca 81037CampaniaItaly department of Clinical Medicine and Surgery University of Naples Federico IINaples 80131CampaniaItaly

BACKGROUNd Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(dPd),encoded by the dPYd *** 7%of the European population is a carrier of dPYd gene polymorphisms associated with reduced dPd enzyme *** To assess the prevalence of dPYd polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal *** A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after dPYd testing;and(2)151 patients treated without dPYd *** the patients in cohort A,15%tested only the dPYd2A polymorphism,19%tested four polymorphisms(dPYd2A,HapB3,c.2846A>T,and dPYd13),and 66%tested five polymorphisms including *** Overall,14.8%of patients were found to be carriers of a dPYd variant,the most common being dPYd6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy *** Although this study had a limited sample size,it provides additional information on the prevalence of dPYd polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.

关键词： dihydropyrimidine dehydrogenase dPYd polymorphisms Fluoropyrimidine Caucasian population Gastrointestinal cancers