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Dysregulation of genes involved in the long-chain fatty acid transport in pancreatic ductal adenocarcinoma

World Journal of Gastrointestinal Oncology 2025年第1期17卷 199-206页

作者： Radu Cristian Poenaru Elena Milanesi Andrei Marian Niculae Anastasia-Maria Dobre Catalina Vladut Mihai Ciocîrlan Daniel Vasile Balaban Vlad Herlea Maria Dobre Mihail Eugen Hinescu Faculty of medicine Carol Davila University of Medicine and PharmacyBucharest 050474Romania department of Radiobiology Victor Babes National Institute of PathologyBucharest 050096Romania department of Pathology Victor Babes National Institute of PathologyBucharest 050096Romania department of Gastroenterology Prof.Dr.Agrippa Ionescu Clinical Emergency HospitalBucharest 011356Romania department of Pathology Fundeni Clinical InstituteBucharest 022258Romania

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United *** for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and *** To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into *** A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical *** genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥*** We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph *** Despite the low number of patients analyzed,these preliminary results seem to be *** lipid metabolism through a broad strategy could be a beneficial way to treat this *** in vitro and in vivo s

关键词： Carcinoma Pancreatic ductal Fatty acid transport Gene expression Biomarkers

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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

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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

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Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology Laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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Exploring gut microbiota as a novel therapeutic target in Crohn’s disease: Insights and emerging strategies

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World Journal of Gastroenterology 2025年第2期31卷 147-156页

作者： Tong Qiao Xian-Hui Wen department of clinical medicine Jinan UniversityGuangzhou 510632Guangdong ProvinceChina College of Life Science and Technology Jinan UniversityGuangzhou 510632Guangdong ProvinceChina

Extensive research has investigated the etiology of Crohn’s disease(CD),encompassing genetic predisposition,lifestyle factors,and environmental ***,the gut microbiome,recognized as the human body’s second-largest gene pool,has garnered significant attention for its crucial role in the patho-genesis of *** paper investigates the mechanisms underlying CD,focusing on the role of‘creeping fat’in disease progression and exploring emerging therapeutic strategies,including fecal microbiota transplantation,enteral nutri-tion,and therapeutic *** fat has been identified as a unique patho-logical feature of CD and has recently been found to be associated with dysbiosis of the gut *** characterize this dysbiotic state by identi-fying key microbiome-bacteria,fungi,viruses,and archaea,and their contributions to CD ***,this paper reviews contemporary therapies,empha-sizing the potential of biological therapies like fecal microbiota transplantation and dietary *** elucidating the complex interactions between host-microbiome dynamics and CD pathology,this article aims to advance our under-standing of the disease and guide the development of more effective therapeutic strategies for managing CD.

关键词： Crohn’s disease Gut microbiome Dysbiosis Creeping fat Fecal microbiota transplantation

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Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

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Neural Regeneration Research 2025年第1期20卷 130-138页

作者： Ilaria Martinelli Jessica Mandrioli Andrea Ghezzi Elisabetta Zucchi Giulia Gianferrari Cecilia Simonini Francesco Cavallieri Franco Valzania department of Neurosciences Azienda Ospedaliero Universitaria di ModenaModenaItaly clinical and experimental medicine Ph.D.Program University of Modena and Reggio EmiliaModenaItaly department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly Neurology Unit Neuromotor&Rehabilitation DepartmentAzienda USL-IRCCS di Reggio EmiliaReggio EmiliaItaly

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal *** the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of *** superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized *** numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this *** this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during *** multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

关键词： amyotrophic lateral sclerosis(ALS) autonomic extramotor genotype-phenotype multisystem involvement Parkinson’s disease sensory SOD1 superoxide dismutase 1 urinary vocal cord palsy

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Gallbladder carcinoma in the era of artificial intelligence: Early diagnosis for better treatment

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 256-259页

作者： Ismail AS Burud Sherreen Elhariri Nabil Eid department of Surgery Clinical CampusIMU UniversitySeremban 70300Negeri SembilanMalaysia department of Anatomy Division of Human BiologySchool of MedicineIMU UniversityKuala Lumpur 57000Kuala LumpurMalaysia

Gallbladder carcinoma(GBC)is the most common malignant tumor of biliary tract,with poor prognosis due to its aggressive nature and limited therapeutic *** detection of GBC is a major challenge,with most GBCs being detected accidentally during cholecystectomy procedures for gallbladder *** letter comments on the recent article by Deqing et al in the World Journal of Gastrointestinal Oncology,which summarized the various current methods used in early diagnosis of GBC,including endoscopic ultrasound(EUS)examination of the gallbladder for high-risk GBC patients,and the use of EUS-guided elasto-graphy,contrast-enhanced EUS,trans-papillary biopsy,natural orifice translu-minal endoscopic surgery,magnifying endoscopy,choledochoscopy,and confocal laser endomicroscopy when necessary for early diagnosis of ***,there is a need for novel methods for early GBC diagnosis,such as the use of artificial intelligence and non-coding RNA biomarkers for improved screening ***,the use of in vitro and animal models may provide critical insights for advancing early detection and treatment strategies of this aggressive tumor.

关键词： Gallbladder carcinoma Endoscopic ultrasound Biopsy Elastography Cho-ledochoscopy Artificial intelligence Non-coding RNAs Screening Animal models In vitro studies

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Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang department of clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina College of Pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes

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Lighting the shades of hidden pain:a role for spinal cord neurons and microglia in vestibulodynia

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Neural Regeneration Research 2025年第10期20卷 2898-2900页

作者： Rosmara Infantino Francesca Gargano Serena Boccella Carmela Belardo Andrea Maria Morace Francesca Guida Sabatino Maione Livio Luongo department of experimental medicine Division of PharmacologyUniversitàdegli Studi della Campania“L.Vanvitelli”Italy UniversitàCampus Bio-medico di Roma RomeItaly

Vulvodynia,a chronic pain disorder affecting the vulvar region,represents a significant challenge in both diagnosis and treatment within the field of women’s *** condition is characterized by chronic pain that significantly affects the quality of life of afflicted *** present perspective paper examines the role of spinal sensitization and microglial activation in vulvodynia.

关键词： pain diagnosis activation

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BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 214-225页

作者： Qin Wang Qing-Rong Li Lei Xu Zi-Chun Yuan Xiao Liu Mao-Ju Tang Man Luo Xiao-Wu Zhong Qiang Ma Xiao-Lan Guo department of clinical Laboratory Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina School of Laboratory medicine&Translational medicine Research Center North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a malignant tumor with high morbidity and mortality,and easy to develop resistance to chemotherapeutic *** are DNA-protein complexes located at the termini of chro-mosomes in eukaryotic cells,which are unreplaceable in maintaining the stability and integrity of ***,an RNA-dependent DNA polymerase,play vital role in telomere length maintain,targeting telomerase is a promising therapeutic strategy for ***150 and KYSE410 cells were cultured and exposed to various concentrations of *** viability was assessed at 48 hours and 72 hours to determine the IC50 *** effects of BIBR1532 on ESCC cell proliferation,migration,and cellular senescence were evaluated using the cell counting kit-8 assay,plate colony formation assay,scratch assay,transwell assay,andβ-galactosidase staining,*** blotting was performed to detect the expression of RESULTS The IC50 values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53μM and 39.59μM,*** values decreased to 37.22μM and 22.71μM,respectively,following a longer exposure of 72 ***1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells,including decreased hTERT expression,inhibition of proliferation and metastasis,and induction of cellular ***,BIBR1532 upregulated the expression of the DDR protein,γ-H2AX,and activated the ataxia telangiectasia and Rad3-related protein(ATR)/check point kinase 1(CHK-1)and ataxia-telangiectasia mutated gene(ATM)/CHK2 ***1532 downregulated the expression of telomere-binding proteins,including telomeric-repeat binding factor 1(TRF1),TRF2,protection of telomeres 1,and TIN2-interacting protein *** a nude mouse xenograft model,BIBR1532 significantly suppressed tumor growth,reduced hTERT expression,and increasedγ-H2AX protein *** and eosin staining of various organs,including the heart,liver,s

关键词： Esophageal squamous cell carcinoma BIBR1532 Human telomerase reverse transcriptase DNA damage response Telomere-binding proteins

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Non-coding RNAs in acute ischemic stroke:from brain to periphery

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Neural Regeneration Research 2025年第1期20卷 116-129页

作者： Shuo Li Zhaohan Xu Shiyao Zhang Huiling Sun Xiaodan Qin Lin Zhu Teng Jiang Junshan Zhou Fuling Yan Qiwen Deng department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina department of Neurology Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina General clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and *** predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain *** innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental *** expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic ***,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and *** particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic *** this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and *** from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

关键词： acute ischemic stroke apoptosis blood–brain barrier damage circular RNAs excitatory toxicity long non-coding RNAs microRNAs neuroinflammation non-coding RNAs oxidative stress

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