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Genes & diseases 2024年第1期11卷 11-14页

作者： Xinghui Li Haiping Wang Yandi Wu Li Zou Shijie Dengg Xintu Fu Tongsheng Huang Conghui Shen Teng Wu Weibin Cai guangdong engineering&technology research center for disease-model animals Laboratory Animal CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China Department of Biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhouGuangdong 510006China guangdong Provincial Key Laboratory of Digestive Cancer research The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China

There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).

关键词： inflammation PEDF hepatic

TMEM63B regulates postnatal development of cochlear sensory epithelia via thyroid hormone signaling

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Journal of Genetics and Genomics 2024年第6期51卷 673-676页

作者： Chang Ye Tian-Zi Zhang Yan-Yu Zang Yun Stone Shi Guoqiang Wan State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of model Animal for disease Study Model Animal Research CenterMedical SchoolNanjing UniversityNanjingJiangsu 210032China guangdong Institute of Intelligence Science and technology ZhuhaiGuangdong 519031China

Sound transmission occurs in the cochlea,a complex and ingenious subdivision in the inner *** structure of the cochlea develops structurally and functionally by the time before two postnatal weeks(the time of hearing onset)in mice(Geal-Dor et al.,1993).Greater epithelial ridge(GER,also known as Kolliker's organ)is a transient cochlear structure containing a group of columnar epithelial supporting cells surrounding the inner hair cells(IHCs).

关键词： cochlear al. supporting

Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

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Neural Regeneration research 2024年第5期19卷 1064-1071页

作者： Mingxiang Ding Lei Jin Boyang Wei Wenping Cheng Wenchao Liu Xifeng Li Chuanzhi Duan Neurosurgery center Department of Cerebrovascular SurgeryThe National Key Clinical SpecialtyThe Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular DiseaseGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationThe Neurosurgery Institute of Guangdong ProvinceZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Cerebrovascular Intervention Zhongshan City People’s HospitalZhongshanGuangdong ProvinceChina

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective *** is a crucial mechanism underlying early brain injury after subarachnoid *** studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and ***,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid *** this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation *** results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological *** explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral *** TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological ***,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte *** summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

关键词： astrocyte early brain injury inflammasome NLRC4 pyroptosis subarachnoid hemorrhage tumor necrosis factor-stimulated gene-6(TSG-6)

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SARS-CoV-2 immunity in animal models

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Cellular & Molecular Immunology 2024年第2期21卷 119-133页

作者： Zhao Chen Yaochang Yuan Qingtao Hu Airu Zhu Fenghua Chen Shu Li Xin Guan Chao Lv Tian Tang Yiyun He Jinling Cheng Jie Zheng Xiaoyu Hu Jingxian Zhao Jincun Zhao Jing Sun State Key Laboratory of Respiratory disease National Clinical Research Centre for Respiratory DiseaseNational Centre for Respiratory MedicineGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510182China GMU-GIBH Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510000China Guangzhou National Laboratory GuangzhouGuangdong 510005China Shanghai Institute for Advanced Immunochemical Studies School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s Hospitalthe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen 518005China

The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its ***-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected *** complications encompass symptoms such as coughing,respiratory distress,fever,infectious shock,acute respiratory distress syndrome(ARDS),and even multiple-organ *** models serve as crucial tools for investigating pathogenic mechanisms,immune responses,immune escape mechanisms,antiviral drug development,and vaccines against ***,various animal models for SARS-CoV-2 infection,such as nonhuman primates(NHPs),ferrets,hamsters,and many different mouse models,have been *** model possesses distinctive features and *** this review,we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection,as well as the corresponding immune responses and applications of these models.A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 ***,we highlighted the current gaps in related research between animal model studies and clinical investigations,underscoring lingering scientific questions that demand further clarification.

关键词： COVID-19 SARS-CoV-2 animal models immune response

Microplastic exposure disturbs sleep structure,reduces lifespan,and decreases ovary size in Drosophila melanogaster

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Zoological research 2024年第4期45卷 805-820页

作者： Wei Yan Zi-Jie Li Zi-Yi Lin Shu-Qin Ji William Ka Fai Tse Zhi-Qiang Meng Chang Liu Lei Li Shenzhen-Hong Kong Institute of Brain Science Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China CAS Key Laboratory of Brain Connectome and Manipulation the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China Laboratory of Developmental Disorders and Toxicology Center for Promotion of International Education and ResearchFaculty of AgricultureKyushu UniversityFukuokaFukuoka 819-0395Japan Shenzhen Key Laboratory of Drug Addiction the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China guangdong Provincial Key Laboratory of Brain Connectome and Behavior Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China

The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and ***,under natural conditions,these effects are not restricted to specific organs or *** whether MP exposure presents a systemic threat to an entire organism,impacting factors such as lifespan,sleep,and fecundity,is *** this study,we investigated the effects of dietary exposure to two different doses of MPs(1–5μm)using the terrestrial model organism Drosophila *** indicated that the particles caused gut damage and remained within the digestive *** MP exposure significantly shortened the lifespan of adult *** short-term exposure disrupted sleep patterns,increasing the length of daytime sleep ***,one week of MP exposure reduced ovary size,with a trend towards decreased egg-laying in mated *** MPs did not penetrate the brain or ovaries,transcriptome analysis revealed altered gene expression in these *** the ovary,Gene Ontology(GO)analysis indicated genotoxic effects impacting inflammation,circadian regulation,and metabolic processes,with significant impacts on extracellular structure-related *** the brain,GO analysis identified changes in pathways associated with proteolysis and carbohydrate ***,this study provides compelling evidence of the systemic negative effects of MP exposure,highlighting the urgent need to address and mitigate environmental MP pollution.

关键词： Microplastics Sleep Lifespan Reproduction Risk assessment Drosophila melanogaster

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

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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

Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis

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research 2024年第2期2023卷 123-137页

作者： Di Xiang Lei Jiang Qiong Yuan Yang Yu Ruiming Liu Meiting Chen Zheng Kuai Wendy Zhang Fan Yang Tingting Wu Zhiyu He Zuhui Ke Wanzi Hong Pengcheng He Ning Tan Yeying Sun Zhen Shi Xuebiao Wei Jianfang Luo Xiaoqiu Tan Yuqing Huo Gangjian Qin Chunxiang Zhang Department of Cardiology Key Laboratory of Medical ElectrophysiologyMinistry of EducationInstitute of Cardiovascular ResearchThe Affiliated Hospital of Southwest Medical UniversitySouthwest Medical UniversityLuzhouSichuan 646000China Department of Biomedical engineering School of Medicine The University of Alabama at BirminghamBirminghamAL 35233USA Department of Cardiology.guangdong Cardiovascular Institute Guangdong Provincial Key Laboratory of Coronary Heart Disease PreventionGuangdong Provincial Institute of Geriatric MedicineGuangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510100China Vascular Biology center Medical College of GeorgiaAugusta UniversityAugustaGA 30912USA

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including *** non-coding RNAs(lncRNAs)are a group of protein expression regulators;however,the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still *** study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and *** identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with *** cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage *** differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid ***,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage *** role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout *** identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage *** provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in *** results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in *** results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.

关键词： inhibited Mor markedly

Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

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Neural Regeneration research 2024年第10期19卷 2281-2289页

作者： Wang Liao Jiana Wei Chongxu Liu Haoyu Luo Yuting Ruan Yingren Mai Qun Yu Zhiyu Cao Jiaxin Xu Dong Zheng Zonghai Sheng Xianju Zhou Jun Liu Department of Neurology The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Special Medical Service center Neuroscience CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangdongGuangdong ProvinceChina Department of Rehabilitation The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Neurology The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Biomedical and Health engineering Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

关键词： Alzheimer's disease APP/PS1 double-transgenic Alzheimer's disease mouse model inflammation intestinal barrier dysfunction magnesium-L-threonate microbiome microbiota-gut-brain axis oxidative stress serum metabolites

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Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1361-1373页

作者： Wen-Feng Luo Yu-Ting Jiao Xiao-Ling Lin Ying Zhao Sheng-Bo Wang Jian Shen Jie Deng Yu-Feng Ye Ze-Ping Han Fang-Mei Xie Jin-Hua He Yu Wan Central Laboratory of Panyu Central Hospital Guangzhou Panyu Central HospitalGuangzhou 511400Guangdong ProvinceChina South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical research Guangzhou Panyu Central HospitalGuangzhou 511400Guangdong ProvinceChina Digestive disease center Guangzhou Panyu Central HospitalGuangzhou 511400Guangdong ProvinceChina Shunde Vocational and Technical College Foshan 528300Guangdong ProvinceChina Medical Imaging Institute of Panyu Guangzhou Panyu Central HospitalGuangzhou 511400Guangdong ProvinceChina

BACKGROUND Colorectal cancer(CRC)is among the most prevalent and life-threatening malignancies ***-2 methylation(mSDC2)testing has emerged as a widely used biomarker for early detection of CRC in stool and serum ***(CRC)is among the most prevalent and life-threatening malignancies ***2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum *** To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in *** A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 *** and specificity for CRC,advanced adenoma(AA)and advanced colorectal neoplasia(ACN)were ***-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the *** A total of 1035 high-risk individuals were included in this study according to established *** them,16 suffered from CRC(1.55%),65 from AA(6.28%)and 189 from non-AAs(18.26%);150 patients were diagnosed with polyps(14.49%).Diagnoses were established based upon colonoscopic and pathological *** of the mSDC2 test for CRC and AA were 87.50%and 40.00%,respectively;specificities were 95.61%for other *** predictive values of the mSDC2 test for CRC,AA and ACN were 16.09%,29.89%and 45.98%,respectively;the negative predictive value for CRC was 99.79%.After adjusting for other high-risk covariates,mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN(P<0.001).CONCLUSION Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high

关键词： Colorectal cancer Syndecan-2 DNA methylation Chinese population

Ganoderma Lucidum Spore Oil enhances the effect of cyclophosphamide via inhibiting programmed death-1 and prolongs the survival of H22 tumor-bearing mice

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Journal of Traditional Chinese Medicine 2024年第4期44卷 652-659页

作者： JIANG Zhaojian CAI Hongfei YUAN Cheng CAO Lin XU Wendong HAN Yaming ZHANG Qin LI Jing WANG Qin LIU Juyan Guangzhou HanFang Pharmaceutical Company Limited National Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug InnovationGuangdong Provincial Key Laboratory of Medicinal Lipids Zhongshan Medical College Sun Yat-sen University Guangzhou Pharmaceutical Holdings Limited National engineering research center of Pharmaceutical Processing technology of Traditional Chinese Medicine and Drug Innovation

OBJECTIVE: To investigate the effect of Ganoderma Lucidum Spore Oil(GLSO) on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide(CTX), and explore the underlying ***: Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GLSO on the tumor growth and survival of animals, and Kaplan-Meier survival analysis was used to analyze the life span. Plasma biochemical examination was used to determine the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST), urea(UREA) and creatinine(CRE). Western blot analysis was performed to detect Programmed Death-1(PD-1), Programmed Death Ligand 1(PD-L1), Janus Kinase 2(JAK2),phosphorylated Signal Transducer and Activator of Transcription 3(p-STAT3), and Signal Transducer and Activator of Transcription 3(STAT3) expression. RESULTS: GLSO increased the anti-tumor effect of CTX and prolonged the survival of H22 tumor-bearing mice treated with CTX. Meanwhile, GLSO increased the thymus index and showed no obvious toxicity to liver functions of animals. GLSO also decreased the level of UREA in H22 tumor-bearing mice treated with CTX. Furthermore, GLSO could inhibit the expression of PD-1 in spleen, which was independent of JAK2 expression and STAT3 phosphorylation. However, GLSO did not affect the expression of PD-L1, JAK2, and p-STAT3 in tumor tissue. CONCLUSION: GLSO could strengthen the anti-tumor effect of CTX and prolong the life span of H22 tumorbearing mice, while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in spleen. Furthermore, these findings implied the promising role of GLSO in combination with CTX to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.

关键词： Ganoderma Lucidum Spore Oil carcinoma, hepatocellular cyclophosphamide programmed cell death 1 receptor survival