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distribution of dNA damage in the human sperm nucleus:implications of the architecture of the sperm head

Asian Journal of Andrology 2020年第4期22卷 401-408页

作者： Silvia González-Rojo cristina fernández-díez Marta Lombó María Paz Herráez department of Molecular Biology Faculty of BiologyUniversidad de LeónCampus de Vegazana s/n LeónLeón 24071Spain

The sperm nucleus is prone to sustain dNA damage before and after ejaculation.distribution of the damage is not homogeneous,and the factors determining differential sensitivity among nuclear regions have not yet been characterized.Human sperm chromatin contains three structural domains,two of which are considered the most susceptible to dNA damage:the histone bound domain,harboring developmental related genes,and the domain associated with nuclear matrix proteins.Using a quantitative polymerase chain reaction(qPCR)approach,we analyzed the number of lesions in genes homeobox A3(HOXA3),homeobox B5(HOXB 5),sex-determining region Y(SRY)-box 2(SOX2),β-GLOBIN,rdNA 18S,and rdNA 28S in human sperm after ultraviolet irradiation(400μW cm−2,10 min),H2O2treatment(250 mmol l−1,20 min),and cryopreservation,which showed differential susceptibility to genetic damage.differential vulnerability is dependent on the genotoxic agent and independent of the sperm nuclear proteins to which the chromatin is bound and of accessibility to the transcription machinery.Immunodetection of 8-hydroxy-2'-deoxyguanosine(8-OHdG)showed that the highest level of oxidation was observed after H2O2treatment.The distribution of oxidative lesions also differed depending on the genotoxic agent.8-OHdG did not colocalize either with histone 3(H3)or with type IIα+βtopoisomerase(TOPO IIα+β)after H2O2treatment but matched perfectly with peroxiredoxin 6(PRdX6),which is involved in H2O2metabolism.Our study reveals that the characteristics of the sperm head domains are responsible for access of the genotoxicants and cause differential degree of damage to nuclear areas,whereas chromatin packaging has a very limited relevance.The histone-enriched genes analyzed cannot be used as biomarkers of oxidative dNA damage.

关键词： biomarkers dNA damage human sperm oxidative stress sperm chromatin sperm quality

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Liquid biopsy for gastric cancer:Techniques,applications,and future directions

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World Journal of Gastroenterology 2024年第12期30卷 1680-1705页

作者： cristina díaz del Arco M Jesús fernández Aceñero Luis Ortega Medina department of Surgical Pathology Health Research Institute of the Hospital Clínico San CarlosHospital Clínico San CarlosMadrid 28040Spain department of Legal Medicine Psychiatry and PathologyUniversidad Complutense de MadridMadrid 28040Spain

After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other metabolites.Additionally,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or stool.LB techniques are diverse,intricate,and variable.They must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential results.Consequently,the implementation of LB in clinical practice still faces several challenges.The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient risk.On the other hand,gastric cancer(GC)is a disease often diagnosed at advanced stages.despite recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these patients.The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients.In this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

关键词： Liquid biopsy Gastric cancer Circulating tumor cells Cell-free dNA Circulating tumor dNA Molecular

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Topical ocular administration of dPP-Ⅳ inhibitors:a new approach for treating diabetes-induced retinal neurodegeneration

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Neural Regeneration Research 2024年第4期19卷 713-714页

作者： Rafael Simó cristina Hernández diabetes and Metabolism Research Unit Vall d’Hebron Research Institute(VHIR) department of Medicine Autonomous University of Barcelona Centro de Investigación Biomédica en Red de diabetes y Enfermedades Metabólicas Asociadas(CIBERdEM) Instituto de Salud CarlosⅢ(ICSⅢ)

Retinal neurodegeneration plays a significant role in the pathogenesis of diabetic retinopathy(dR),the leading cause of preventable blindness.In fact,the American diabetes Association has defined dR as a highly specific neurovascular complication(Solomon et al.,2017).Therefore,it is no longer acceptable to consider dR as merely a microvascular complication.In this regard,the term diabetic retinal disease(dRd)has been proposed as a broader term comprising microangiopathy and neurodegeneration.However,there are currently no treatments available that directly target the neurodegenerative changes of dR.This paper will give new insights into the translational research in this field with particular emphasis on glucagon-like peptide 1/dipeptidyl peptidase IV(GLP-1/dPP-IV)inhibitors.

关键词： neurodegeneration ocular insight

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Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2233-2240页

作者： Joaquina Martínez-Galán cristina Jiménez-Luna Isabel Rodriguez Elisabeth Maza Carlos García-Collado Antonio Rodríguez-fernández Javier Luis López-Hidalgo Octavio Caba department of Medical Oncology Virgen de las Nieves University HospitalGranada 18014Spain Instituto de Investigación Biosanitaria Ibs.GranadaGranada 18012Spain Institute of Biopathology and Regenerative Medicine(IBIMER) University of GranadaGranada 18016Spain Pharmacogenetics Unit Virgen de las Nieves University HospitalGranada 18014Spain department of Medicina Nuclear Virgen de las Nieves University HospitalGranada 18014Spain department of Anatomía Patológica Virgen de las Nieves University HospitalGranada 18014Spain

BACKGROUNd Metastatic pancreatic ductal adenocarcinoma(PdAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PdAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PdAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PdAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PdAC.To our knowledge,this is the first reported case of a patient with metastatic PdAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PdAC patients most likely to benefit from this immunotherapy.

关键词： Pancreatic ductal adenocarcinoma Lung cancer Immunotherapy Pembrolizumab Programmed cell death protein-1 Case report

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Circadian rhythm disruption and retinal dysfunction:a bidirectional link in Alzheimer’s disease?

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Neural Regeneration Research 2024年第9期19卷 1967-1972页

作者： Laura Carrero desireéAntequera cristina Municio Eva Carro Group of Neurodegenerative diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpainNetwork Center for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain Phd Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurobiology of Alzheimer’s disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpainNetwork Centre for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain

dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic nucleus.Notably,Alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of Alzheimer’s disease patients,followed/associated by structural and functional disturbances.However,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.

关键词： Alzheimer’s disease amyloid circadian rhythm neurodegeneration retina

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Biodegradability of bioplastics in different aquatic environments:A systematic review

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Journal of Environmental Sciences 2024年第8期142卷 169-181页

作者： Maria cristina Lavagnolo Valentina Poli Anna Maria Zampini Valentina Grossule department of Civil Environmental and Architectural Engineering-Laboratory of Environmental EngineeringUniversity of PadovaLungargine Rovetta 8Padova 35100Italy

Bioplastics were first introduced as environmentally friendly materials,with properties similar to those of conventional plastics.A bioplastic is defined as biodegradable if it can be decomposed into carbon dioxide under aerobic degradation,or methane and CO_(2)under anaerobic conditions,inorganic compounds,and new cellular biomass,by the action of naturally occurring microorganisms.This definition however does not provide any information on the environmental conditions,timescale and extent at which decomposition processes should occur.With regard to the aquatic environment,recognized standards have been established to assess the ability of plastics to undergo biodegradation;however,these standards fail to provide clear targets to be met to allow labelling of a bioplastic as biodegradable.Moreover,these standards grant the user an extensive leeway in the choice of process parameters.For these reasons,the comparison of results deriving from different studies is challenging.The authors analysed and discussed the degree of biodegradability of a series of biodegradable bioplastics in aquatic environments(both fresh and salt water)using the results obtained in the laboratory and from on-site testing in the context of different research studies.Biochemical Oxygen demand(BOd),CO_(2)evolution,surface erosion and weight loss were the main parameters used by researchers to describe the percentage of biodegradation.The results showed a large variability both in weight loss and BOd,even when evaluating the same type of bioplastics.This confirms the need for a reference range of values to be established with regard to parameters applied in defining the biodegradability of bioplastics.

关键词： Biodegradation Bioplastic Plastic Natural environment Plastic waste

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Insights on ZEB1-AS1: emerging role from cancer to neurodegeneration

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Neural Regeneration Research 2024年第6期19卷 1187-1188页

作者： Stephana Carelli Federica Rey Erika Maghraby cristina Cereda Pediatric Research Center “Romeo ed Enrica Invernizzi” Department of Biomedical and Clinical Sciences University of Milan 2. Center of Functional Genomics and Rare Diseases Department of Pediatrics Buzzi Children's Hospital department of Biology and Biotechnology “L.Spallanzani” University of Pavia

Implications for lncRNAs in the central nervous system: Transcriptional dysregulation is a key contributor to the pathogenesis of a wide range of diseases and long non-coding RNAs(lncRNAs) are highly expressed in the nervous system. Indeed, amongst the over 50,000 lncRNAs expressed in the human genome, more than 40% are specifically expressed in the brain where their roles in brain development, neuron functions, maintenance,

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Physical activity and amyloid beta in middle-aged and older adults:A systematic review and meta-analysis

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Journal of Sport and Health Science 2024年第2期13卷 133-144页

作者： María Rodriguez-Ayllon Patricio Solis-Urra cristina Arroyo-ávila Miriam álvarez-Ortega Pablo Molina-García cristina Molina-Hidalgo Manuel Gómez-Río Belinda Brown Kirk I.Erickson Irene Esteban-Cornejo department of Epidemiology Erasmus University Medical Center RotterdamRotterdamGD 3015the Netherlands department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18071Spain Faculty of Education and Social Sciences Universidad Andres BelloVina del Mar 2531015Chile department of Nuclear Medicine Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain Physical Medicine and Rehabilitation Service Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain department of Psychology University of PittsburghPittsburghPA 15260USA Centre for Healthy Ageing Health Futures InstituteMurdoch UniversityMurdochWA 6150Australia School of Medical and Health Sciences Edith Cowan UniversityJoondalupWA 6027Australia Advent Health Research Institute Neuroscience Institute OrlandoOrlandoFL 32803USA Physiopathology of Obesity and Nutrition Research Center(CIBERobn) Institute of Health Carlos Ⅲ(ISCⅢ)Madrid 28029Spain

Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels modulation.We aimed to explore the relationship between physical activity and Aβin middle-aged and older adults.Methods:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTdiscus was performed from inception to April 28,2022.Studies were eligible if they included physical activity and Aβdata in adults aged 45 years or older.Multi-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβlevels.Results:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and blood.Higher physical activity was positively associated with Aβonly in the CSF(Estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older adults.However,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies.In observational studies,higher levels of physical activity were positively associated with Aβonly in CSF.Therefore,further research is needed to understand the modulating role of physical act

关键词： Aging Cognitive impairment dementia Exercise PET

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Contrast-enhanced guided endoscopic ultrasound procedures

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World Journal of Gastroenterology 2024年第17期30卷 2311-2320页

作者： Marcel Ioan Gheorghiu Andrada Seicean cristina Pojoga Claudia Hagiu Radu Seicean Zeno Sparchez department of Gastroenterology “Prof.Dr.Octavian Fodor”Regional Institute of Gastroenterology and Hepatology"Iuliu Hatieganu"University of Medicine and PharmacyCluj-Napoca 400162ClujRomania department of Clinical Psychology and Psychotherapy International Institute for Advanced Study of Psychotherapy and Applied Mental HealthBabeș-Bolyai UniversityCluj-Napoca 400375ClujRomania The First Surgical Clinic "Iuliu Hatieganu"University of Medicine and PharmacyCluj Napoca 400006ClujRomania

Contrast-enhanced endoscopic ultrasound(CH-EUS)can overcome the limi-tations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours.despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions,further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS.This review details the knowledge based on the available data on contrast-guided procedures.The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions,which occur in select cases.Additionally,the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage,and patients who have nonvisualized vessels that need to be highlighted via doppler EUS are presented.Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours,in which case CH-EUS can be used to reveal the incomplete tumour destruction.

关键词： Endosonography Contrast-enhanced endoscopic ultrasound Tissue acquisition Fine needle aspiration Fine needle biopsy drainage Pancreatic fluid collections Biopsy Pancreas

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Epidemiology,therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont,Italy

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 761-772页

作者： Christian Bracco Marta Gallarate Marco Badinella Martini Corrado Magnino Salvatore d'Agnano Roberta Canta Giulia Racca Remo Melchio cristina Serraino Valentina Polla Mattiot Giovanni Gollè Luigi Fenoglio department of Internal Medicine Santa Croce e Carle General HospitalCuneo 12100Italy department of Medical Sciences "City of Health and Science"University HospitalTorino 10100Italy

BACKGROUNd Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide.It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate.HCC patients have increasingly complex and constantly changing characteristics,thus up-to-date and comprehensive data are fundamental.AIM To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019.METHOdS In this retrospective study,we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at"Santa Croce e Carle"Hospital in Cuneo(Italy)between 1 January 2010 and 31 december 2019.To highlight possible changes in HCC patterns over the 10-year period,we split the population into two 5-year groups,according to the diagnosis period(2010-2014 and 2015-2019).RESULTS Of the 328 HCC patients who were included(M/F 255/73;mean age 68.9±11.3 years),154 in the first period,and 174 in the second.Hepatitis C virus infection was the most common HCC risk factor(41%,135 patients).The alcoholic etiology rate was 18%,the hepatitis B virus infection etiology was 5%,and the non-viral/non-alcoholic etiology rate was 22%.The Child-Pugh score distribution of the patients was:class A 75%,class B 21%and class C 4%.The average Mayo end-stage liver disease score was 10.6±3.7.A total of 55 patients(17%)were affected by portal vein thrombosis and 158(48%)by portal hypertension.The average nodule size of the HCC was 4.6±3.1 cm.A total of 204 patients(63%)had more than one noduled 92%(305 patients)had a non-metastatic stage of the disease.The Barcelona Clinic Liver Cancer(BCLC)staging distribution of all patients was:4%very early,32%early,23%intermediate,34%advanced,and 7%terminal.Average survival rate was 1.6±0.3 years.Only 20%of the patients underwent treatment.Age,presence of ascites,BCLC stage and therapy were predictors of a better prognosis(P<0.01).A c

关键词： Hepatocellular carcinoma Hepatitis virus Alcoholic hepatitis Non-alcoholic fatty liver disease diagnosis Etiology Treatment

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