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Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

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Journal of Biomedical research 2024年第4期38卷 348-357页

作者： Mengfan Guo Jingyuan Liu Yujuan Zhang Jingjing Gu Junyi Xin Mulong Du Haiyan Chu Meilin Wang Hanting Liu Zhengdong Zhang Departments of Environmental Genomics and Genetic Toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthJiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public Health/Institute of Clinical Researchthe Affiliated Taizhou People's Hospital of Nanjing Medical UniversityNanjing Medical UniversityNanjingJiangsu 211166China Departments of Environmental Genomics and Genetic Toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthJiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjingJiangsu 211166China Department of Biostatistics Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer *** using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and *** results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

关键词： O-glycosylation genetic variants immune status gastric cancer

Brain circuits for retching-like behavior

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National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic medical Sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland Laboratory (Guangzhou Regenerative Medicine and health Guangdong Laboratory) Department of Neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University State Key Laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science Laboratory National institute of Biological Sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+*** Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

*** model of riboflavin transporter deficiency(RTD)disorder reveals deficits in synaptic transmission and movement

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Genes & Diseases 2024年第4期11卷 120-123页

作者： Ramesh K.Narayanan Gonzalo Perez-siles Kamila A.Marzec Alexandra Boyling Brent Neumann Manoj P.Menezes Marina L.Kennerson Northcott Neuroscience Laboratory ANZAC Research Institute-Sydney Local Health DistrictSydneyNSW 2139Australia Sydney medical School University of SydneySydneyNSw 2050Australia ANZAC research institute-Sydney Local health District SydneyNSW 2139Australia Neuroscience program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVictoria 3800Australia TY Nelson Department of Neurology and Neurosurgery and Kids Neuroscience Children's Hospital at WestmeadWestmeadSydneyNSW2145Australia Paediatrics and Child health The University of SydneySydneySydneyNSW 2145Australia Molecular Medicine Laboratory Concord General Repatriation HospitalSydneyNSW 2139Australia

Riboflavin transporter deficiency(RTD),previously known as Brown-Vialetto-Van Laere syndrome,is a childhoodonset neurodegenerative disorder characterized by sensory and motor neuron degeneration causing ataxia,muscle weakness,optic atrophy,and respiratory *** in SLC52A2 and SLC52A3,solute carrier family members that encode riboflavin(RF)transporters RFVT2 and RFVT3,are known to cause RTD types 2 and 3,respectively.

关键词： RTD degeneration TD

Current status of early gastric cancer screening research

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cancer Biology & Medicine 2024年第3期21卷 218-222页

作者： Can Hu Li Yuan Xiangdong Cheng Department of Gastric surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Key Laboratory of Prevention Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang ProvinceHangzhou 310022China Zhejiang Provincial research Center for Upper Gastrointestinal Tract cancer Zhejiang Cancer HospitalHangzhou 310022China

Gastric cancer is a predominant threat to the health and well-being of China's residents. Data from the World health Organization(WHO) in 2020 revealed that gastric cancer in China notably accounted for 44.0% of new c... 详细信息

关键词： cancer Gastric gastric

Identification of TMEM217 as a novel prognostic biomarker and potential therapeutic target in acute myeloid leukemia

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Genes & Diseases 2024年第4期11卷 90-93页

作者： Yunying Yao Zhizhou Xi Min Wu Bo Jiao Jiaming Gao Donghe Li Xi Xie Pengfei Xu Jiaoyang Li Lei Yan Ruibao Ren Ping Liu Shanghai institute of Hematology State Key Laboratory for Medical GenomicsNational Research Center for Translational MedicineCollaborative Innovation Center of HematologyRuijin Hospital affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China International Center for Aging and cancer Hainan Medical UniversityHaikouHainan 570102China

Despite remarkable advances in molecular and cell biology of acute myeloid leukemia(AML),AML patients still frequently relapse and have low 5-year overall survival(OS)rates.1 It is worth noting that a recent study from the registry or clinical trial compilation has reported an improvement in the OS of adult AML patients,especially those under 60 years of age.

关键词： acute myeloid leukemia

Developing fertility control for rodents: a framework for researchers and practitioners

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Integrative Zoology 2024年第1期19卷 87-107页

作者： Giovanna MASSEI Jens JACOB Lyn A.HINDS Botstiber institute for Wildlife Fertility Control Department of Environment and GeographyUniversity of YorkHeslingtonYorkUK Rodent research Institute for Epidemiology and Pathogen DiagnosticsJulius Kühn–Institute(JKI)Federal Research Institute for Cultivated PlantsMünsterGermany CSIRO health and Biosecurity CanberraACTAustralia

Fertility control is often heralded as a humane and effective technique for management of overabundant wildlife,including *** intention is to reduce the use of lethal and inhumane methods,increase farm productivity and food security as well as reduce disease transmission,particularly of *** developed a framework to guide researchers and stakeholders planning to assess the effectiveness of a potential contraceptive agent for a particular *** guidelines describe the overarching research questions which must be sequentially addressed to ensure adequate data are collected so that a contraceptive can be registered for use in broad-scale rodent *** framework indicates that studies should be undertaken iteratively and,at times,in parallel,with initial research being conducted on(1)laboratory-based captive assessments of contraceptive effects in individuals;(2)simulation of contraceptive delivery using bait markers and/or surgical sterilization of different proportions of afield-based or enclosure population to determine how population dynamics are affected;(3)development of mathematical models which predict the outcomes of different fertility control scenarios;and(4)implementation of large-scale,replicated trials to validate contraceptive efficacy under various management-scalefield *** some circumstances,fertility control may be most effective when integrated with other methods(*** culling).Assessment of non-target effects,direct and indirect,and the environmental fate of the contraceptive must also be *** fertility control for a species is a resource-intensive commitment but will likely be less costly than the ongoing environmental and economic impacts by rodents and rodenticides in many contexts.

关键词： captive studies field applications modeling oral contraceptive delivery population management rodents

Assessment of molecular markers and marker-assisted selection for drought tolerance in barley(Hordeum vulgare L.)

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Journal of Integrative Agriculture 2024年第1期23卷 20-38页

作者： Akmaral Baidyussen Gulmira Khassanova Maral Utebayev Satyvaldy Jatayev Rystay Kushanova Sholpan Khalbayeva Aigul Amangeldiyeva Raushan Yerzhebayeva KulpashBulatova Carly Schramm Peter Anderson Colin L.D.Jenkins Kathleen LSoole Yuri Shavrukov Faculty of Agronomy S.Seifullin Kazakh AgroTechnical Research UniversityAstana 010000Kazakhstan A.I.Barayev research and Production Centre of Grain Farming Shortandy 021601Kazakhstan Kazakh research institute of Agriculture and Plant Growing AlmalybakAlmaty District 040909Kazakhstan College of Science and Engineering Biological SciencesFlinders UniversityAdelaideSA 5042Australia

This review updates the present status of the field of molecular markers and marker-assisted selection(MAS),using the example of drought tolerance in *** accuracy of selected quantitative trait loci(QTLs),candidate genes and suggested markers was assessed in the barley genome *** common strategies are described for molecular marker development,candidate gene identification and verification,and their possible applications in MAS to improve the grain yield and yield components in barley under drought *** strategies are based on the following five principles:(1)Molecular markers are designated as genomic‘tags’,and their‘prediction’is strongly dependent on their distance from a candidate gene on genetic or physical maps;(2)plants react differently under favourable and stressful conditions or depending on their stage of development;(3)each candidate gene must be verified by confirming its expression in the relevant conditions,e.g.,drought;(4)the molecular marker identified must be validated for MAS for tolerance to drought stress and improved grain yield;and(5)the small number of molecular markers realized for MAS in breeding,from among the many studies targeting candidate genes,can be explained by the complex nature of drought stress,and multiple stress-responsive genes in each barley genotype that are expressed differentially depending on many other factors.

关键词： barley candidate genes drought tolerance gene verification via expression grain yield marker-assisted selection(MAS) molecular markers quantitative trait loci(QTLs) strategy for MAS

Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner Thoracic Surgery research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of Thoracic Surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： Pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

Gut microbiota-derived short-chain fatty acids and depression:deep insight into biological mechanisms and potential

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General Psychiatry 2024年第1期37卷 17-32页

作者： Junzhe Cheng Hongkun Hu Yumeng Ju Jin Liu Mi Wang Bangshan Liu Yan Zhang Department of Psychiatry National Clinical Research Center for Mental DisordersSecond Xiangya Hospital of Central South UniversityChangshaHunanChina Clinical Medicine Eight-Year program Xiangya School of MedicineCentral South UniversityChangshaHunanChina Mental health institute of Central South University China National Technology Institute on Mental DisordersHunan Key Laboratory of Psychiatry and Mental HealthHunan Medical Center for Mental HealthChangshaHunanChina Department of Mental health Center Xiangya Hospital of Central South UniversityChangshaHunanChina

The gut microbiota is a complex and dynamic ecosystem known as the second brain'.Composing the microbiota-gut-brain axis,the gut microbiota and its metabolites regulate the central nervous system through neural,endocrine and immune pathways to ensure the normal functioning of the organism,tuning individuals'health and disease ***-chain fatty acids(SCFAs),the main bioactive metabolites of the gut microbiota,are involved in several neuropsychiatric disorders,including *** have essential effects on each component of the microbiota-gut-brain axis in *** the present review,the roles of major SCFAs(acetate,propionate and butyrate)in the pathophysiology of depression are summarised with respect to chronic cerebral hypoperfusion,neuroinflammation,host epigenome and neuroendocrine *** remarks on the biological mechanisms related to gut microbiota will hopefully address the clinical value of microbiota-related treatments for depression.

关键词： alterations inflammation perfusion