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Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

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Oncology Research 2024年第4期32卷 691-702页

作者： JIJIE XIAO HONG XIAO YUJUN CAI JIANWEI LIAO JUE LIU LIN YAO SHAOLIN LI Department of Radiology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai510900China Department of Ultrasound The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou528405China PCFM Lab of Ministry of Education School of Materials Science and EngineeringGuangzhou510275China

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient *** has shown great potential in the treatment of ***,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma *** dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor ***,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of *** laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by ***,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor ***,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

关键词： Immunotherapy Osteosarcoma Nanodrug Photodynamic therapy CD47

A twist in the tale:global insights into archaeal box C/D RNA-guided 2′-O-methylation

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Science China(Life Sciences) 2024年第4期67卷 849-850页

作者： Bin Li Jianhua Yang MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China The Fifth affiliated hospital Sun Yat-sen UniversityZhuhai 519000China

The 2′-O-methylation of RNA stands as a dynamic and multifaceted modification,wielding significant influence over the regulation of RNA function,stability,and interactions within the cellular context(sun et al.,2023)... 详细信息

关键词： twist insight

A novel mouse model of PEDF-associated serious liver inflammation,hepatic tumorigenesis and cardiovascular injury mimics human nonalcoholic steatohepatitis

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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

TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization

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Neuroscience Bulletin 2024年第1期40卷 17-34页

作者： Siying Qu Shengfeng Hu Huiting Xu Yongjian Wu Siqi Ming Xiaoxia Zhan Cheng Wang Xi Huang Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China The State Key Laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Allergy and Clinical ImmunologyThe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China Department of Laboratory Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Division of Nephrology Department of Medicinethe Fifth Affliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)***,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in ***,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse *** knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE ***,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE *** conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.

关键词： Multiple sclerosis Experimental autoimmune encephalomyelitis T helper 17 Triggering receptor expressed on myeloid cells 2

Early proactive monitoring of DNA-thioguanine in patients with Crohn’s disease predicts thiopurine-induced late leucopenia in NUDT15/TPMT normal metabolizers

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World Journal of Gastroenterology 2024年第12期30卷 1751-1763页

作者： Ting Yang Kang Chao Xia Zhu Xue-Ding Wang Sumyuet Chan Yan-Ping Guan Jing Mao Pan Li Shao-Xing Guan Wen Xie Xiang Gao Min Huang School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Institute of Clinical Pharmacology Sun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Department of Gastroenterology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655Guangdong ProvinceChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080Guangdong ProvinceChina Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261United States

BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of *** optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia *** To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite *** leucopenia was defined as a leukocyte countsensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.

关键词： Thiopurine-induced late leucopenia DNA-thioguanine 6-thioguanine nucleotide Proactive therapeutic drug monitoring Crohn’s disease

Reconstructing cell lineage trees with genomic barcoding:approaches and applications

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Journal of Genetics and Genomics 2024年第1期51卷 35-47页

作者： Zizhang Li Wenjing Yang Peng Wu Yuyan Shan Xiaoyu Zhang Feng Chen Junnan Yang Jian-Rong Yang Advanced Medical Technology Center The First Affiliated HospitalZhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China Department of Genetics and Biomedical Informatics Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China Key Laboratory of Tropical Disease Control Ministry of EducationSun Yat-sen UniversityGuangzhouGuangdong 510080China

In multicellular organisms,developmental history of cell divisions and functional annotation of terminal cells can be organized into a cell lineage tree(CLT).The reconstruction of the CLT has long been a major goal in developmental biology and other related *** technological advancements,especially those in editable genomic barcodes and single-cell high-throughput sequencing,have sparked a new wave of experimental methods for reconstructing *** we review the existing experimental approaches to the reconstruction of CLT,which are broadly categorized as either image-based or DNA barcode-based *** addition,we present a summary of the related literature based on the biological insight pro-vided by the obtained ***,we discuss the challenges that will arise as more and better CLT data become available in the near *** barcoding-based CLT reconstructions and analyses,due to their wide applicability and high scalability,offer the potential for novel biological discoveries,especially those related to general and systemic properties of the developmental process.

关键词： Cell lineage tree Developmental regulation Biotechnology Computational biology

Plasma microRNA-15a/16-1-based machine learning for early detection of hepatitis B virus-related hepatocellular carcinoma

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High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p

Liver Research 2024年第2期8卷 105-117页

作者： Huan Wei Songhao Luo Yanhua Bi Chunhong Liao Yifan Lian Jiajun Zhang Yuehua Huang Guangdong Provincial Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen University Guangzhou China School of Mathematics Sun Yat-sen University Guangzhou China School of Public Health Sun Yat-sen University Guangzhou China Guangdong Province Key Laboratory of Computational Science Sun Yat-sen University Guangzhou China Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen University Guangzhou China

Background and aims Hepatocellular carcinoma (HCC), which is prevalent worldwide and has a high mortality rate, needs to be effectively diagnosed. We aimed to evaluate the significance of plasma microRNA-15a/16-1 (miR-15a/16) as a biomarker of hepatitis B virus-related HCC (HBV-HCC) using the machine learning model. This study was the first large-scale investigation of these two miRNAs in HCC plasma samples. Methods Using quantitative polymerase chain reaction, we measured the plasma miR-15a/16 levels in a total of 766 participants, including 74 healthy controls, 335 with chronic hepatitis B (CHB), 47 with compensated liver cirrhosis, and 310 with HBV-HCC. The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein (AFP). Lastly, to validate the diagnostic efficiency of miR-15a/16, we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC. Results Plasma miR-15a/16 was significantly decreased in HCC than in all control groups ( P sensitivity, and average precision (AP) for the detection of HCC were higher for miR-15a (AUC = 0.80, 67.3%, AP = 0.80) and miR-16 (AUC = 0.83, 79.0%, AP = 0.83) than for AFP (AUC = 0.74, 61.7%, AP = 0.72). Combining miR-15a/16 with AFP increased the AUC to 0.86 (sensitivity 85.9%) and the AP to 0.85 and was significantly superior to the other markers in this study ( P < 0.05 for all), as further demonstrated by the detection error tradeoff curves. Moreover, miR-15a/16 impressively showed potent diagnostic power in early-stage, small-tumor, and AFP-negative HCC. A validation cohort confirmed these results. Lastly, the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16. Conclusions We developed and validated a plasma miR-15a/16-based machine learning model, which exhibited better diagnostic perfo

关键词： Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) microRNA-15a microRNA-16-1 Biomarker Machine learning Pseudotemporal ordering

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Science China(Life Sciences) 2024年第2期67卷 286-300页

作者： Bi-Ang Kang Hua-Ming Li Ya-Ting Chen Meng-Jie Deng Yan Li Yue-Ming Peng Jian-Jun Gao Zhi-Wei Mo Jia-Guo Zhou Zhi-Jun Ou Jing-Song Ou Division of Cardiac Surgery Cardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases Guangzhou 510080China NHC key Laboratory of Assisted Circulation(sun yat-sen university) Guangzhou 510080China Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases Guangzhou 510080China Division of Vascular Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Pharmacology Cardiac and Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Division of Hypertension and Vascular Diseases Department of CardiologyCardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China

We previously demonstrated that normal high-density lipoprotein(nHDL)can promote angiogenesis,whereas HDL from patients with coronary artery disease(d HDL)is dysfunctional and impairs *** plays a critical role in angiogenesis,and HDL regulates ***,it is unclear whether n HDL and d HDL regulate angiogenesis by affecting *** cells(ECs)were treated with n HDL and d HDL with or without an autophagy ***,endothelial nitric oxide synthase(e NOS)expression,miRNA expression,nitric oxide(NO)production,superoxide anion(O2^(·-))generation,EC migration,and tube formation were evaluated.n HDL suppressed the expression of miR-181a-5p,which promotes autophagy and the expression of e NOS,resulting in NO production and the inhibition of O2^(·-)generation,and ultimately increasing in EC migration and tube formation.d HDL showed opposite effects compared to n HDL and ultimately inhibited EC migration and tube *** found that autophagy-related protein 5(ATG5)was a direct target of ***5 silencing or miR-181a-5p mimic inhibited n HDL-induced autophagy,e NOS expression,NO production,EC migration,tube formation,and enhanced O2^(·-)generation,whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of d ***5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null(LDLr^(-/-))mice when compared to C57BL/6 ***5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr^(-/-)*** together,nHDL was able to stimulate autophagy by suppressing miR-181a-5p,subsequently increasing e NOS expression,which generated NO and promoted *** contrast,d HDL inhibited angiogenesis,at least partially,by increasing miR-181a-5p expression,which decreased autophagy and e NOS expression,resulting in a decrease in NO production and an increase in O2^(·-)*** findings reveal a nov

关键词： high-density lipoprotein angiogenesis autophagy ATG5 miRNA endothelial nitric oxide synthase

New insights into the correlations between circulating tumor cells and target organ metastasis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 211-233页

作者： Qinru Zhan Bixia Liu Xiaohua Situ Yuting Luo Tongze Fu Yanxia Wang Zhongpeng Xie Lijuan Ren Ying Zhu Weiling He Zunfu Ke Department of Pathology The First Affiliated Hospital of Sun Yat-sen University510000 GuangzhouGuangdongP.R.China Institute of Precision Medicine The First Affiliated Hospital of Sun Yat-sen University510000 GuangzhouGuangdongP.R.China Zhongshan School of Medicine Sun Yat-sen University510000 GuangzhouGuangdongP.R.China Department of Radiology The First Affiliated Hospital of Sun Yat-sen University510000 GuangzhouGuangdongP.R.China Department of Microbiology and Immunology Weill Cornell MedicineNew YorkNY 10065USA School of Medicine Xiang’an Hospital of Xiamen UniversityXiamen University361000 XiamenFujianP.R.China

Organ-specific metastasis is the primary cause of cancer patient *** distant metastasis of tumor cells to specific organs depends on both the intrinsic characteristics of the tumor cells and extrinsic factors in their *** an intermediate stage of metastasis,circulating tumor cells(CTCs)are released into the bloodstream from primary and metastatic *** harboring aggressive or metastatic features can extravasate to remote sites for continuous colonizing growth,leading to further *** the past decade,numerous studies demonstrated that CTCs exhibited huge clinical value including predicting distant metastasis,assessing prognosis and monitoring treatment response et ***,increasingly numerous experiments are dedicated to identifying the key molecules on or inside CTCs and exploring how they mediate CTC-related organ-specific *** on the above molecules,more and more inhibitors are being developed to target CTCs and being utilized to completely clean CTCs,which should provide promising prospects to administer advanced ***,the application of various nanomaterials and microfluidic technologies in CTCs enrichment technology has assisted to improve our deep insights into the phenotypic characteristics and biological functions of CTCs as a potential therapy target,which may pave the way for us to make practical clinical *** the present review,we mainly focus on the role of CTCs being involved in targeted organ metastasis,especially the latest molecular mechanism research and clinical intervention strategies related to CTCs.

关键词： metastasis organs insight