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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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Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams department of Biology University of PisaPisaItaly department of clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

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Predicting colorectal adenomatous polyps in patients with chronic liver disease: A novel nomogram

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World Journal of Gastroenterology 2025年第2期31卷 71-84页

作者： Yu-Qin Li Wen-Tao Kuai Lin Chen Ming-Hui Zeng Xue-Mei Tao Jia-Xin Han Yue-Kui Wang Lian-Xin Xu Li-Ying Ge Yong-Gang Liu Shuang Li Liang Xu Yu-Qiang Mi clinical School of the Second People’s Hospital Tianjin Medical UniversityTianjin 300192China department of Hepatology Tianjin Second People’s HospitalTianjin 300192China department of Pathology Clinical School of the Second People’s HospitalTianjin 300110China Endoscopy Center Tianjin Second People’s HospitalTianjin 300192China

BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for *** To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were *** data including laboratory results,colonoscopy findings,and pathology reports were *** variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic *** performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve *** The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin *** novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation *** curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of *** The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.

关键词： Metabolic dysfunction associated steatotic liver disease Fatty liver Chronic liver disease Colorectal adenomas Hepatitis Risk factors

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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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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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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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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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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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Hemogram-derived ratios as prognostic markers for major adverse cardiovascular events in patients with non-ST-segment elevation myocardial infarction

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World Journal of Methodology 2025年第2期15卷 125-136页

作者： Emir Bećirović Minela Bećirović SabinaŠegalo Amir Bećirović Semir Hadžić Kenana Ljuca Emsel Papić Lamija Ferhatbegović Malik Ejubović Amira JagodićEjubović Amila Kovčić ArminŠljivo Emir Begagić department of Intensive Care University Clinical Center TuzlaTuzla 75000Bosnia and Herzegovina department of Nephrology University Clinical Center TuzlaTuzla 75000Bosnia and Herzegovina department of Laboratory Technologies Faculty of Health SciencesUniversity of SarajevoSarajevo 71000Bosnia and Herzegovina department of Endocrinology University Clinical Center TuzlaTuzla 75000Bosnia and Herzegovina School of Medicine University of TuzlaTuzla 75000Bosnia and Herzegovina department for Internal Diseases and Hemodialysis Canton Hospital ZenicaZenica 72000Bosnia and Herzegovina department of Internal Medicine Canton Hospital ZenicaZenica 72000Bosnia and Herzegovina department of Radiotherapy University Clinical Center TuzlaTuzla 75000Bosnia and Herzegovina department of Cardiology University Clinical Center SarajevoSarajevo 72000Bosnia and Herzegovina department of General Medicine University of ZenicaSchool of MedicineZenica 72000Bosnia and Herzegovina

BACKGROUND Non-ST segment elevation myocardial infarction(NSTEMI)poses significant challenges in clinical management due to its diverse *** the prognostic role of hematological parameters and derived ratios in NSTEMI patients could aid in risk stratification and improve patient *** To evaluate the predictive value of hemogram-derived ratios for major adverse cardiovascular events(MACE)in NSTEMI patients,potentially improving clinical *** A prospective,observational cohort study was conducted in 2021 at the Internal Medicine Clinic of the University Hospital in Tuzla,Bosnia and *** study included 170 patients with NSTEMI,who were divided into a group with MACE and a control group without ***,the MACE group was subdivided into lethal and non-lethal groups for prognostic *** hematological parameters,an additional 13 hematological-derived ratios(HDRs)were monitored,and their prognostic role was *** Hematological parameters did not significantly differ between non-ST segment elevation myocardial infarction(NSTEMI)patients with MACE and a control group at T1 and ***,significant disparities emerged in HDRs among NSTEMI patients with lethal and non-lethal outcomes ***,neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)were elevated in lethal ***,C-reactive protein-to-lymphocyte ratio(CRP/Ly)at T1(>4.737)demonstrated predictive value[odds ratio(OR):3.690,P=0.024].Both NLR at T1(>4.076)and T2(>4.667)emerged as significant predictors,with NLR at T2 exhibiting the highest diagnostic performance,as indicated by an area under the curve of 0.811(95%CI:0.727-0.859)and OR of 4.915(95%CI:1.917-12.602,P=0.001),emphasizing its important role as a prognostic *** This study highlights the significant prognostic value of hemogram-derived indexes in predicting MACE among NSTEMI *** follow-up,NLR,PLR,and CRP/Ly off

关键词： Hemogram-derived ratios Prognostic markers Neutrophil-to-lymphocyte ratio Myocardial infarction

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