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DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Congenital Heart Diseases

Congenital Heart Disease 2024年第2期19卷 247-256页

作者： Shuliang Xia Huikang Tao Shixin Su Xinxin Chen Li Ma Jianru Li Bei Gao Xumei Liu Lei Pi Jinqing Feng Fengxiang Li Jia Li Zhiwei Zhang Guangdong Provincial People’s Hospital Southern Medical UniversityGuangzhou510100China Department of Cardiovascular Surgery Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhou510623China Department of Pediatric Cardiology Guangdong Cardiovascular InstituteGuangdong Provincial Key Laboratory of South China Structural Heart DiseaseGuangzhou510100China clinical Physiology Laboratory Institute of PediatricsGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangzhou510623China Department of Echocardiogram Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhou510623China Department of Pediatrics Washington University School of MedicineSt.LouisMO63130USA clinical Biological Resource Bank of Guangzhou Women and Children’s Medical Center Guangzhou Medical UniversityGuangzhou510623China

Aims:Multiple genes and environmental factors are known to be involved in congenital heart disease(CHD),but epigenetic variation has received little ***(MZ)twins with CHD provide a unique model for exploring this *** order to investigate the potential role of Deoxyribonucleic Acid(DNA)methyla-tion in CHD pathogenesis,the present study examined DNA methylation variation in MZ twins discordant for CHD,especially ventricular septal defect(VSD).Methods and Results:Using genome-wide DNA methylation profiles,we identified 4004 differentially methylated regions(DMRs)in 18 MZ twin pairs discordant for CHD,and 2826 genes were *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed a list of CHD-associated *** further investigate the role of DNA methylation in VSD,data from 7 pairs of MZ twins with VSD were *** identified 1614 DMRs corresponding to 1443 genes associated with arrhythmogenic right ventricular cardiomyopathy,cyclic guanosine monopho-sphate-protein kinase G(cGMP-PKG)signaling pathway by KEGG analysis,and cell-cell adhesion,calcium ion transmembrane transport by GO analysis.A proportion of DMR-associated genes were involved in calcium signaling *** methylation changes of calcium signaling genes might be related to VSD ***:CHD is associated with differential DNA methylation in MZ *** may be etiologically linked to DNA methylation,and methylation of calcium signaling genes may be involved in the development of VSD.

关键词： Congenital heart disease monozygotic twins methylation modification epigenetics

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p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

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Neural Regeneration research 2024年第10期19卷 2299-2309页

作者： Lemeng Feng Chao Wang Cheng Zhang Wulong Zhang Weiming Zhu Ye He Zhaohua Xia Weitao Song National clinical research Center for Geriatric Diseases Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Eye Center of Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina

Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

关键词： ferroptosis glaucoma glutamate excitotoxicity p38 MAPK retinal ganglion cell SB202190

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P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

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Neural Regeneration research 2024年第8期19卷 1849-1856页

作者： Meihui He Mingfang Xia Qian Yang Xingyi Chen Haibo Li Xiaobo Xia Eye Center of Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina National clinical research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of ***,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal *** the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of ***,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult *** rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell ***,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia *** together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

关键词： Achaetescute complex-like 1a(Ascl1a) metabolomics Müller glia p-aminobenzoic acid(PABA) retina regeneration zebrafish

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Method for the extraction of circulating nucleic acids based on MOF reveals cell-free RNA signatures in liver cancer

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National Science Review 2024年第1期11卷 94-106页

作者： Yuqing Sun Haixin Yu Shaoqing Han Ruoxi Ran Ying Yang Yongling Tang Yuhao Wang Wenhao Zhang Heng Tang Boqiao Fu Boshi Fu Xiaocheng Weng Song-Mei Liu Hexiang Deng Shuang Peng Xiang Zhou College of Chemistry and Molecular Sciences Key Laboratory of Biomedical Polymers-Ministry of Education Wuhan University Department of Digestive Surgical Oncology Union Hospital Tongji Medical College Huazhong University of Science and Technology Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of clinical Laboratory Center for Gene Diagnosis and Program of Clinical Laboratory Zhongnan Hospital of Wuhan University College of Chemistry and Materials Science Hubei Engineering University Department of Pharmacology School of Pharmacy China Medical University Taikang Center for Life and Medical Sciences Wuhan University Department of Hematology Zhongnan Hospital of Wuhan University

Cell-free RNA(cf RNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cf RNA isolation technologies due to the low abundance and instability of cf ***, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids(containing cf RNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework(MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cf RNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cf RNA in serum from patients with liver cancer was described and a cf RNA signature with six cf RNAs was identified to diagnose liver cancer with high diagnostic efficiency(area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.

关键词： MOF circulating cell-free RNA biomarker liver cancer diagnosis

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CD147 Facilitates the Pathogenesis of Psoriasis through Glycolysis and H3K9me3 Modification in Keratinocytes

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research 2024年第1期2023卷 509-523页

作者： Chao Chen Xiaoqing Yi Panpan Liu Jie Li Bei Yan Detian Zhang Lei Zhu Pian Yu Lei Li Jiaxiong Zhang Yehong Kuang Shuang Zhao Wu Zhu Cong Peng Xiang Chen Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunanChina National Engineering research Center of Personalized Diagnostic and Therapeutic Technology ChangshaHunanChina Furong Laboratory ChangshaHunanChina Hunan Key Laboratory of Skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South UniversityChangshaHunanChina National clinical research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal *** elevated glycolysis flux has been reported in psoriasis,the molecular mechanisms underlying its pathogenesis remain *** investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis,observing its high expression in psoriatic skin lesions of humans and imiquimod(IMQ)-induced mouse *** mouse models,genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic *** found that CD147 interacted with glucose transporter 1(Glut1).Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in *** CD147-knockout mice and keratinocytes,oxidative phosphorylation was increased in the epidermis,indicating CD147's pivotal role in glycolysis reprogramming during pathogenesis of *** non-targeted and targeted metabolic techniques,we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid(α-KG).

关键词： CD147 pathogenesis markedly

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Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data

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Cancer Biology & Medicine 2024年第8期 712-723页

作者： Yu Zhang Chao Sheng Zhangyan Lyu Hongji Dai Fangfang Song Fengju Song Yubei Huang Kexin Chen Department of Epidemiology and Biostatistics Key Laboratory of Molecular Cancer Epidemiology Key Laboratory of Prevention and Control of Human Major Diseases Ministry of Education National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin Medical University

Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and ***: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk ***: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94; 0.81, 0.73±0.90; mortality: 0.75, 0.64±0.87; 0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk ***: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

关键词： Colorectal cancer incidence mortality polygenic risk score screening

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Early-onset and later-onset cancer: trends, risk factors, and prevention in Northern China: a prospective study

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Science China Life Sciences 2024年

作者： Tong Liu Chen-An Liu Qing-Song Zhang Qi Zhang Yi-Ming Wang Meng-Meng Song Shi-Qi Lin Li Deng Shou-Ling Wu Han-Ping Shi Department of Gastrointestinal Surgery Department of Clinical Nutrition Beijing Shijitan Hospital Capital Medical University National clinical research Center for Geriatric Diseases Xuanwu Hospital Capital Medical University Key Laboratory of Cancer FSMP for State Market Regulation Laboratory for clinical Medicine Capital Medical University Department of General Surgery Kailuan General Hospital Department of Genetics Yale School of Medicine Department of Hepatobiliary Surgery Kailuan General Hospital Cardiovascular research Institute University of California Department of Cardiology Kailuan General Hospital

The characteristics of early-onset(onset age <50 years) and later-onset(onset age ≥50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer(624 with early-onset cancer and 6,117 with later-onset cancer)and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early-and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early-and later-onset cancer by cancer type. Populationattributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation,and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including earlyonset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

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Emerging microfluidics for the modeling and treatment of arthritis

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Engineered Regeneration 2024年第2期5卷 153-169页

作者： Nengjie Yang Chi Sun Chen Dong Yuting Huang Yujuan Zhu Zhifeng Gu Department of Rheumatology Research Center of ImmunologyAffiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong 226001China Department of Geriatrics Affiliated Hospital of Nantong UniversityNantong UniversityNantong 226001China Department of Dermatology Affiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong 226001China research Center of clinical Medicine Research Center of ImmunologyAffiliated Hospital of Nantong UniversityNantong 226001China

Microfluidic is a technology that allows the precise control of fluid in a *** its advantages of high throughput and low cost,microfluidic technology has achieved good performance in various fields in recent *** is a general term for a variety of joint diseases,which can be clinically manifested as joint pain and swelling,seriously affecting people’s physical and mental *** present,the causes of arthritis disease are still unknown,and existing disease models and treatment methods are still limited,so more treatments need to be *** organ chip is a cutting-edge technology to build a bionic human organ model,which can reflect the structure and function characteristics of human organs by simulating the physiological environment of tissues and cells in *** paper reviews the application of microfluidic technology in the modeling and treatment of arthritis,hoping to open up a new vision for the study of arthritis.

关键词： Microfluidics Arthritis Organ on a chip Drug delivery system Drug screening

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Present situation of minimally invasive surgical treatment for early gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1154-1165页

作者： Chun-Yan Li Yi-Feng Wang Li-Kang Luo Xiao-Jun Yang The First clinical Medical School Lanzhou UniversityLanzhou 730000Gansu ProvinceChina The First clinical Medicine College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery clinical Centre Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina The Second Department of General Surgery Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Lanzhou University People's clinical Hospital Lanzhou 730000Gansu ProvinceChina Gansu research Center of Prevention and Control Project for Digestive Oncology Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Gansu Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

Minimally invasive surgery is a kind of surgical operation,which is performed by using professional surgical instruments and equipment to inactivate,resect,repair or reconstruct the pathological changes,deformities and wounds in human body through micro-trauma or micro-approach,in order to achieve the goal of treatment,its surgical effect is equivalent to the traditional open surgery,while avoiding the morbidity of conventional surgical *** addition,it also has the advantages of less trauma,less blood loss during operation,less psychological burden and quick recovery on patients,and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer *** minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer(EGC):endoscopic mucosal resection(EMR),underwater EMR(UEMR),endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR),endoscopic submu-cosal excavation(ESE),submucosal tunnel endoscopic resection,laparoscopic and endoscopic cooperative surgery(LECS);Among them,EMR,EFTR and LECS technologies have a wide range of applications and different modific-ations have been derived from their respective surgical operations,such as band-assisted EMR(BA-EMR),conven-tional EMR(CEMR),over-the-scope clip-assisted EFTR,no-touch EFTR,the inverted LECS,closed LECS,and so *** new and improved minimally invasive surgeries are more precise,specific and effective in treating different types of EGC.

关键词： Minimally invasive surgery Early gastric cancer Endoscopic mucosal resection Endoscopic full-thickness resection Laparoscopic and endoscopic cooperative surgery

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Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

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Cellular & Molecular Immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu Pengfei Yuan Shuaixin Gao Thomas S.Fulford Adam P.Uldrich Catherine C.L Wong Wensheng Wei Biomedical Pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for Precision Medicine Multi-Omics research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunology program Peter MacCallum Cancer CentreMelbourneVICAustralia State Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer *** found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T *** coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

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