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Parasites of the liver:A global problem?

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World Journal of Gastroenterology 2024年第30期30卷 3554-3559页

作者： Vladislav V Tsukanov Alexander V Vasyutin julia l Tonkikh Clinical Department of the Digestive System Pathology of Adults and Children Federal Research Center“Krasnoyarsk Science Center”of the Siberian Branch of the Russian Academy of SciencesScientific Research Institute of Medical Problems of the NorthKrasnoyarsk 660022Russia

Parasitic liver diseases can be caused by trematodes,cestodes,nematodes,and *** pathology is significant because millions of people in different parts of the world have liver parasites,which can manifest themselves in the development of inflammation,liver cysts,cholecystitis,cholelithiasis,pancreatitis and liver cirrhosis that are often threatening their *** International Agency for Research on Cancer considers three species of trematodes,Schistosoma haematobium,Opisthorchis viverrini and Clonorchis sinensis,to be *** modern examination methods,in some cases including extensive screening of large populations,are required for diagnosing liver *** of parasitic liver diseases is differentiated and can involve a combination of surgical and therapeutic *** is no doubt that the clinical and epidemiological scale allows one to regard parasitic liver diseases as a global healthcare problem.

关键词： liver Parasites Epidemiology Diagnosis Clinics Treatment Echinococcosis Opisthorchiasis Fascioliasis Schistosomiasis

Inhibition of M2 tumor-associated macrophages polarization by modulating the Wnt/β-catenin pathway as a possible liver cancer therapy method

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World Journal of Gastroenterology 2024年第40期30卷 4399-4403页

作者： Vladislav V Tsukanov julia l Tonkikh Edward V Kasparov Alexander V Vasyutin Clinical Department of the Digestive System Pathology of Adults and Children Federal Research Center“Krasnoyarsk Science Center”of the Siberian Branch of the Russian Academy of SciencesScientific Research Institute of Medical Problems of the NorthKrasnoyarsk 660022Russia

The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol *** deter-mines great attention to the development and improvement of methods for early diagnosis and treatment of liver *** et al presented a study in the World Journal of Gastroenterology,in which they showed that the use of the traditional Chinese medicine Calculus bovis(CB)can suppress tumor growth in mice by inhibiting M2 tumor-associated macrophages(TAM)through modulating the activity of the Wnt/β-catenin *** interaction of CB components with the Wnt/β-catenin pathway,M2 TAM polarization,and tumor dynamics were studied using network pharmacology,transcriptomics,and molecular *** is now generally accepted that the polarization of TAM and the differentiation of the functions of M1 and M2 phagocytes are of great importance for the progression of *** is assumed that M2 TAM promote proliferation and migration of tumor *** to medicinally influence the Wnt/β-catenin pathway in order to modulate phagocyte polarization now belong to one of the most promising areas of immunotherapy of oncological ***,the work of the Chinese authors deserves attention and further development.

关键词： liver cancer Treatment Calculus bovis Tumor-associated macrophages M2 tumor Macrophage polarization Wnt/β-catenin pathway

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

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World Journal of Diabetes 2024年第8期15卷 1717-1725页

作者： Jorge M Molina Patricia G Medina Rita A Gomez julia R Herrera Nancy l Martínez Brenda Hernández Yesenia García Department of Endocrinology Children’s Hospital Federico GomezMexico 06720Mexico National Medical Center"Siglo XXI" UMAE Hosp EspecialidadesUnidad Invest Med Epidemiol ClinMexican Social Security InstituteMexico 06720Mexico Research Division UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIMexican Institute of Social SecurityMexico 06720Mexico Epidemiology Research Unit in Endocrinology and Nutrition Federico Gómez Children’s HospitalMexico 06720Mexico Department of Endocrinology Comprehensive Health Unit for Trans PersonsMexico 11340Mexico

BACKGROUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-GAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin *** To evaluate anti-GAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of *** This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 ***,blood pressure,glucose,insulin,C-peptide,glycated hemoglobin A1c,and lipid profiles were *** was used to measure anti-GAD65,anti-IA2,and anti-Zn8T *** statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.Plly *** There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 *** presence of anti-GAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,*** the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-GAD65 odds ratio(OR):2.42(1.112–5.303,P=0.026);anti-IA2:OR:1.55(0.859–2.818,P=0.105);and anti-Zn8T:OR:7.32(2.039–26.279,P=0.002).CONClUSION Anti-GAD65 positivity was high in our ***-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

关键词： Diabetes Obesity Adolescents Autoimmunity Beta cell Insulin requirements

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

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World Journal of Gastroenterology 2024年第13期30卷 1815-1835页

作者： Samantha Sharma Naresh Singh Anita Ahmed Turk Isabella Wan Akshay Guttikonda julia lily Dong Xinna Zhang Mateusz Opyrchal Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202United States Division of Hematology/Oncology Department of MedicineIndiana University School of MedicineIndianapolisIN 46202United States Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202United States

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical *** considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely *** the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint *** aimed at blocking immune checkpoints such as PD-1,PD-l1,and CTlA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor *** therapies thus have shown promising results in many clinical trials alone or in *** efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical *** trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair ***,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC *** this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the *** review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in *** underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

关键词： Colorectal cancer Immune checkpoint inhibitors Clinical trials Immunotherapy Microsatellite instability Microsatellite stability DNA mismatch repair

Woody plant taxonomic,functional,and phylogenetic diversity decrease along elevational gradients in Andean tropical montane forests:Environmental filtering and arrival of temperate taxa

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Plant Diversity 2024年第4期46卷 491-501页

作者： Guillermo Bañares-de-Dios Manuel J.Macía Gabriel Arellano Íñigo Granzow-de la Cerda julia Vega-álvarez Itziar Arnelas Carlos I.Espinosa Norma Salinas luis Cayuela Departamento de Biología y Geología Física y Química InorgánicaUniversidad Rey Juan CarlosCalle Tulipán s/nMóstolesMadridES-28933Spain Departamento de Biología Área de BotánicaUniversidad Autónoma de MadridCalle Darwin 2MadridES-28049Spain Centro de Investigación en Biodiversidad y Cambio Global(CIBC-UAM) Universidad Autónoma de MadridCalle Darwin 2MadridES-28049Spain Ecology and Evolutionary Biology University of MichiganAnn ArborMI 48109USA Oikobit llC ***AlbuquerqueNM87120USA Real Jardín Botánico–CSIC Plaza Murillo 2MadridES-28014Spain Departamento de Biología Animal EcologíaParasitologíaEdafología y Química AgrícolaUniversidad de SalamancaCalle Donantes de Sangre s/nSalamancaES-37007Spain Departamento de Biodiversidad Ecología y EvoluciónUniversidad Complutense de MadridCalle JoséAntonio Nováis 12Ciudad UniversitariaES-28040Spain Departamento de Ciencias Biológicas y Agropecuarias Universidad Técnica Particular de LojaA.P.11-01-608 LojaEcuador Sección Química Pontificia Universidad Católica del PerúA.P.Lima 32LimaPeru ECI School of Geography and EnvironmentUniversity of OxfordOX13QYOxfordshireUnited Kingdom Instituto de Investigación en Cambio Global(IICG-URJC) Universidad Rey Juan CarlosCalle Tulipán s/nMóstolesMadridES-28933Spain

Mountains are paramount for exploring biodiversity patterns due to the mosaic of topographies and climates encompassed over short *** research has traditionally focused on taxonomic diversity when investigating changes along elevational gradients,but other facets should be *** first time,we simultaneously assessed elevational trends in taxonomic,functional,and phylogenetic diversity of woody plants in Andean tropical montane forests and explored their underlying ecological and evolutionary *** investigation covered four transects(traversing ca.2200 m a.s.l.) encompassing 114 plots of 0.1 ha across a broad latitudinal range(ca.10°).Using Hill numbers to quantify abundance-based diversity among 37,869 individuals we observed a consistent decrease in taxonomic,functional,and phylogenetic diversity as elevation increased,although the decrease was less pronounced for higher Hill *** exception was a slight increase in phylogenetic diversity when dominant species were *** decrease in taxonomic and functional diversity might be attributed to an environmental filtering process towards highlands,where the increasingly harsher conditions exclude species and functional ***,the differences in steepness decrease between Hill orders suggest that rare species disproportionately contribute to functional *** phylogenetic diversity the shifting elevational trend between Hill orders indicates a greater than previously considered influence in central Andean highlands of tropical lowlands originated species with strong niche conservatism relative to distantly related temperate *** could be explained by a decreasing presence and abundance of temperate,extratropical taxa towards the central Andes relative to northern or southern Andes,where they are more prevalent.

关键词： Altitudinal gradients Andes Environmentalﬁltering Out of the Tropical lowlands Functional rarity Tropical Niche Conservatism

Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

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Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang loujin Slitin Jakob Neef Shashank S.Chepurwar Regina Célia Mingroni Netto Karina lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarlab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil laboratório de Otorrinolaringologia/lIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

Multiparametric analysis of colorectal cancer immune responses

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World Journal of Gastroenterology 2018年第27期24卷 2995-3005页

作者： julia KH leman Sarah K Sandford Janet l Rhodes Roslyn A Kemp Department of Microbiology and Immunology University of Otago

Colorectal cancer(CRC) is a heterogeneous disease, with a diverse and plastic immune cell infiltrate. These immune cells play an important role in regulating tumour growth-progression or elimination. Some populations of cells have a strong correlation with disease-free survival, making them useful prognostic markers. In particular, the infiltrate of CD3^+ and CD8^+ T cells into CRC tumours has been validated worldwide as a valuable indicator of patient prognosis. However, the heterogeneity of the immune response, both between patients with tumours of different molecular subtypes, and within the tumour itself, necessitates the use of multiparametric analysis in the investigation of tumour-specific immune responses. This review will outline the multiparametric analysis techniques that have been developed and applied to studying the role of immune cells in the tumour, with a focus on colorectal cancer. Because much of the data in this disease relates to T cell subsets and heterogeneity, we have used T cell populations as examples throughout. Flow and mass cytometry give a detailed representation of the cells within the tumour in a single-cell suspension on a per-cell basis. Imaging technologies, such as imaging mass cytometry, are used to investigate increasing numbers of markers whilst retaining the spatial and structural information of the tumour section and the infiltrating immune cells. Together, the analyses of multiple immune parameters can provide valuable information to guide clinical decision-making in CRC.

关键词： Colorectal cancer Flow cytometry Immune cells Multiparametric analysis Immunohistochemistry Mass cytometry Microscopy

Behavioural and energetic consequences of competition among three overwintering swan(Cygnus spp.)species

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Avian Research 2021年第4期12卷 707-721页

作者： Kevin A.Wood julia l.Newth Geoff M.Hilton Eileen C.Rees Wildfowl&Wetlands Trust SlimbridgeGloucestershire GL27BTUnited Kingdom Centre for Ecology and Conservation/Environment and Sustainabil-ity Institute College of Life and Environmental SciencesUniversity of ExeterExeter TR109EZUnited Kingdom Department of Zoology University of CambridgeDowning StreetCambridge CB23EJUnited Kingdom

Background:Winter numbers of the northwest European population of Bewick's Swans(Cygnus columbianus bewickii)declined recently by c.40%.During the same period,numbers of two sympatric and ecologically-similar congeners,the Mute Swan(Cygnus olor)and Whooper Swan(Cygnus cygnus)showed increases or *** has been suggested that these opposing population trends could have a causal relationship,as Mute and Whooper Swans are larger and competitively dominant to Bewick's Swans in foraging *** so,effects of competition of Mute and Whooper Swans on Bewick's Swans should be detectable as measurable impacts on behaviour and ***:Here,we studied the diurnal behaviour and energetics of 1083 focal adults and first-winter juveniles("cygnets")of the three swan species on their winter grounds in eastern *** analysed video recordings to derive time-activity budgets and these,together with estimates of energy gain and expenditure,were analysed to determine whether individual Bewick's Swans altered the time spent on key behaviours when sharing feeding habitat with other swan species,and any consequences for their energy expenditure and net energy ***:All three swan species spent a small proportion of their total time(0.011)on aggressive interactions,and these were predominantly intraspecific(≥0.714).Mixed-effects models indicated that sharing feeding habitat with higher densities of Mute and Whooper Swans increased the likelihood of engaging in aggression for cygnet Bewick's Swans,but not for *** levels of interspecific competition decreased the time spent by Bewick's Swan cygnets on foraging,whilst adults showed the opposite *** among low densities of conspecifics(ls/km^(2)),individual Bewick's Swans spent more time on vigilance in the presence of higher densities of Mute and Whooper Swans,whilst individuals within higher density Bewick's Swan flocks showed the opposite ***,we found no evide

关键词： Avian behaviour Energy expenditure Ethology Interference competition Interspecific interactions Time activity budgets Video observations

PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptide in rat liver transplantation

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World Journal of Gastroenterology 2006年第7期12卷 1049-1055页

作者： Uwe Grutzner Melanie Keller Michael bach Alexandra K Kiemer Herbert Meissner Manfred Bilzer Stefan Zahler Alexander l Gerbes Angelika M Vollmar Institute for Surgical Research Klinikum GroBhadernUniversity of MunichD-81377 MunichGermany Department of Pharmacy University of MunichD-81377 MunichGermany Department Institute of Pathology University of MunichD-81377 MunichGermany

AIM： To investigate the in vivo effect of atrial natriuretic peptide （ANP） and its signaling pathway during orthotopic rat liver transplantation.METHODS： Rats were infused with NaCI, ANP （5 μg/ kg）, wortmannin （WH, 16μg/kg）, or a combination of both for 20 min. livers were stored in UW solution （4℃） for 24 h, transplanted and reperfused. Apoptosis was examined by caspase-3 activity and TUNEl staining. Phosphorylation of Akt and Bad was visualized by Western blotting and phospho-Akt-localization by confocal microscopy.RESUlTS： ANP-pretreatment decreased caspase-3 activity and TUNElopositive cells after cold ischemia, indicating antiapoptotic effects of ANP in vivo. The an- tiapoptotic signaling of ANP was most likely caused by phosphorylation of Akt and Bad, since pretreatment with PI 3-kinase inhibitor WM abrogated the ANP-induced reduction of caspase-3 activity. Interestingly, analysis of liver tissue by confocal microscopy showed translocation of phosphorylated Akt to the plasma membrane of hepa- tocytes evoked by ANP.CONClUSION： ANP activates the PI-3-kinase pathway in the liver in vivo leading to phosphorylation of Bad an event triggering antiapoptotic signaling cascade in ischemic liver.

关键词： Bad Apoptosis Hormonal preconditioning Ischemia reperfusion injury