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CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

Oncology Research 2024年第2期32卷 261-272页

作者： SHUANGSHUANG ZENG XI CHEN QIAOLI YI ABHIMANYU THAKUR HUI yanG yuanliang yan SHAO LIU Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha410008China Pritzker School of Molecular Engineering Ben May Department for Cancer ResearchUniversity of ChicagoChicagoILUSA Department of Pathology The Second Affiliated Hospital of Shandong First Medical UniversityTaian271000China

Finding biomarkers for immunotherapy is an urgent issue in cancer *** retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human ***,there is limited research on the relationship between CRABP2 and immunotherapy *** study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor ***,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell *** expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in *** validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been *** models showed an increase in tumor weight and *** analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of *** conclusion,this study provides new insights into the role of CRABP2 in immunotherapy *** findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM *** research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.

关键词： CRABP2 Melanoma PD-1 Cancer-associated fibroblasts Immune infiltration

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Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1637-1650页

作者： yuanliang yan Shangjun Zhou Xi Chen Qiaoli Yi Songshan Feng Zijin Zhao Yuanhong Liu Qiuju Liang Zhijie Xu Zhi Li Lunquan Sun Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410008China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangsha 410008China Department of Pathology Xiangya HospitalCentral South UniversityChangsha 410008China Xiangya Cancer Center Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Molecular Radiation Oncology Hunan Province Changsha 410008China institute of Cancer Research National Clinical Research Center for Geriatric Disorders(Xiangya)Xiangya HospitalCentral South UniversityChangsha 410008China

Temozolomide(TMZ)represents a standard-of-care chemotherapeutic agent in glioblastoma(GBM).However,the development of drug resistance constitutes a significant hurdle in the treatment of malignant *** specific innovative approaches,such as immunotherapy,have shown favorable clinical outcomes,the inherent invasiveness of most gliomas continues to make them challenging to ***,there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug *** investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors.A total of 648 proteins exhibiting significant differential expression were *** Set Enrichment Analysis(GSEA)unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OXIDATIONS between the primary and recurrent *** through glioma tissue arrays and the Xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate(IP3)kinase B(ITPKB)in the recurrence group,correlating with poor survival in glioma *** TMZ-resistant cells,the depletion of ITPKB led to an increase in reactive oxygen species(ROS)related to NADPH oxidase(NOX)activity and restored cell sensitivity to ***,the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ***,in turn,elevated ITPKB stability and impaired ROS ***,ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse *** findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target forTMZ-resistant GBM.

关键词： TMZ homeostasis impaired

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Dynamic m6A-ncRNAs association and their impact on cancer pathogenesis, immune regulation and therapeutic response

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Genes & Diseases 2023年第1期10卷 135-150页

作者： yuanliang yan Jinwu Peng Qiuju Liang Xinxin Ren Yuan Cai Bi Peng Xi Chen Xiang Wang Qiaoli Yi Zhijie Xu Department of Pharmacy Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Pathology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Pathology Xiangya Changde HospitalChangdeHunan 415000China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Center for Molecular Medicine Xiangya HospitalKey Laboratory of Molecular Radiation Oncology of Hunan ProvinceCentral South UniversityChangshaHunan 410008China

Several types of modifications have been proven to participate in the metabolism and processing of different RNA types,including non-coding RNAs(ncRNAs).N-6-methyladenosine(m6A)is a dynamic and reversible RNA modification that is closely involved in the ncRNA homeostasis,and serves as a crucial regulator for multiple cancer-associated signaling *** ncRNAs usually regulate the epigenetic modification,mRNA transcription and other biological processes,displaying enormous roles in human *** this review,we summarized the significant implications of m6A-ncRNA interaction in various types of *** particular,the interplay between m6A and ncRNAs in cancer pathogenesis and therapeutic resistance are being widely *** also discussed the relevance of m6A-ncRNA interaction in immune regulation,followed by the interference on cancer immunotherapeutic *** addition,we briefly highlighted the computation tools that could identify the accurate features of m6A methylome among *** summary,this review would pave the way for a better understanding of the biological functions of m6A-ncRNA crosstalk in cancer research and treatment.

关键词： Cancer Immune regulation N-6-Methyladenosine Non-coding RNAs Therapeutic response

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The implication of pyroptosis in cancer immunology:Current advances and prospects

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Genes & Diseases 2023年第6期10卷 2339-2350页

作者： Wei Liu Jinwu Peng Muzhang Xiao Yuan Cai Bi Peng Wenqin Zhang Jianbo Li Fanhua Kang Qianhui Hong Qiuju Liang yuanliang yan Zhijie Xu Department of Pathology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Orthopedic Surgery The Second Hospital University of South ChinaHengyangHunan 421001China Department of Pathology Xiangya Changde HospitalChangdeHunan 415000China Department of Burn and Plastic Surgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Pharmacy Xiangya HospitalCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Pyroptosis is a regulated cell death pathway involved in numerous human diseases,especially malignant *** studies have identified multiple pyroptosis-associated signaling molecules,like caspases,gasdermin family and *** addition,increasing in vitro and in vivo studies have shown the significant linkage between pyroptosis and immune regulation of ***-associated biomarkers regulate the infiltration of tumor immune cells,such as CD4^(+) and CD8^(+) T cells,thus strengthening the sensitivity to therapeutic *** this review,we explained the relationship between pyroptosis and cancer immunology and focused on the significance of pyroptosis in immune *** also proposed the future application of pyroptosis-associated biomarkers in basic research and clinical practices to address malignant *** of the underlying mechanisms and biological functions of pyroptosis is critical for immune response and cancer immunotherapy.

关键词： Cancer immunology Immune response Immunotherapy Pyroptosis Inflammasomes

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Multi-omics analysis reveals the pivotal role of phytohormone homeostasis in regulating maize grain water content

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The Crop Journal 2024年第4期12卷 1081-1092页

作者： yuanliang Liu Manman Li Jianju Liu Suining Deng yan Zhang Yuanfeng Xia Baoshen Liu Mingliang Xu State Key Laboratory of Plant Environmental Resilience/College of Agronomy and Biotechnology/National Maize Improvement Center/Center for Crop Functional Genomics and Molecular Breeding China Agricultural UniversityBeijing 100193China College of Agronomy/State Key Laboratory of Crop Biology Shandong Agricultural UniversityTai’an 271018ShandongChina Institute of Agricultural Biotechnology Jilin Academy of Agricultural SciencesGongzhuling 136100JilinChina Maize Research Institute Jilin Academy of Agricultural SciencesGongzhuling 136100JilinChina

Grain water content(GWC)is a key determinant for mechanical harvesting of maize(Zea mays).In our previous research,we identified a quantitative trait locus,qGWC1,associated with GWC in ***,we examined near-isogenic lines(NILs)NILL and NILH that differed at the qGWC1 *** GWC in NILL was primarily attributed to reduced grain water weight(GWW)and smaller fresh grain size,rather than the accumulation of dry *** difference in GWC between the NILs became more pronounced approximately 35 d after pollination(DAP),arising from a faster dehydration rate in *** an integrated analysis of the transcriptome,proteome,and metabolome,coupled with an examination of hormones and their derivatives,we detected a marked decrease in JA,along with an increase in cytokinin,storage forms of IAA(IAA-Glu,IAA-ASP),and IAA precursor IPA in immature NILL *** kernel development,genes associated with sucrose synthases,starch biosynthesis,and zein production in NILL,exhibited an initial up-regulation followed by a gradual down-regulation,compared to those in *** discovery highlights the crucial role of phytohormone homeostasis and genes related to kernel development in balancing GWC and dry matter accumulation in maize kernels.

关键词： Grain water content Maize kernel Phytohormone homeostasis

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Applying artificial intelligence for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3393-3405页

作者： Zhijie Xu Xiang Wang Shuangshuang Zeng Xinxin Ren yuanliang yan Zhicheng Gong Department of Pathology Xiangya HospitalCentral South UniversityChangsha 410008China Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410008China Institute for Rational and Safe Medication Practices National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangsha 410008China Center for Molecular Medicine Xiangya HospitalKey Laboratory of Molecular Radiation Oncology of Hunan ProvinceCentral South UniversityChangsha 410008China

Artificial intelligence(AI)is a general term that refers to the use of a machine to imitate intelligent behavior for performing complex tasks with minimal human intervention,such as machine learning;this technology is revolutionizing and reshaping *** has considerable potential to perfect health-care systems in areas such as diagnostics,risk analysis,health information administration,lifestyle supervision,and virtual health *** terms of immunotherapy,AI has been applied to the prediction of immunotherapy responses based on immune signatures,medical imaging and histological *** features could also be highly useful in the management of cancer immunotherapy given their ever-increasing performance in improving diagnostic accuracy,optimizing treatment planning,predicting outcomes of care and reducing human resource *** this review,we present the details of AI and the current progression and state of the art in employing AI for cancer ***,we discuss the challenges,opportunities and corresponding strategies in applying the technology for widespread clinical ***,we summarize the impact of AI on cancer immunotherapy and provide our perspectives about underlying applications of AI in the future.

关键词： Artificial intelligence Cancer immunotherapy Machine learning Diagnostics

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CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

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Journal of Genetics and Genomics 2024年第2期51卷 184-196页

作者： yan Shi Chunyan Cao Yiheng Zeng yuanliang Ding Long Chen Fuze Zheng Xuejiao Chen Fanggui Zhou Xiefeng yang Jinjing Li Liuqing Xu Guorong Xu Minting Lin Hiroyuki Ishiura Shoji Tsuji Ning Wang Zhiqiang Wang Wan-Jin Chen Kang yang Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China Department of Neurology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China The First Affiliated Hospital College of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan 471000China Department of Neurology Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujian 363000China Department of Neurology Jian'ou Municipal Hospital of Fujian ProvinceJian'ouFujian 353100China Department of Radiology First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China Department of Neurology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Neurology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan Institute of Medical Genomics International University of Health and WelfareChiba 286-0048Japan

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with ***,since only three patients from a single family were reported,it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/***,using repeat-primed-polymerase chain reaction and long-read sequencing,we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1,typically presenting with oculopharyngodistal *** CGG repeat expansions range from 161 to 669 repeat *** of the patients present with ptosis,restricted eye movements,dysphagia,dysarthria,and diffuse limb muscle *** one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance *** biopsies from three patients show a myopathic pattern and rimmed *** of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity,suggesting that RNA toxicity and mitochondrial dysfunction may contribute to *** study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

关键词： Oculopharyngeal myopathy with leukoencephalopathy Oculopharyngodistal myopathy CGG repeat expansion Rimmed vacuoles

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从涿鹿之战看中国史前水利与华夏文明

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中国水利水电科学研究院学报 2019年第6期17卷 401-406页

作者：颜元亮中国水利水电科学研究院水利史研究所北京100038

涿鹿之战发生于公元前3000年左右,是我国历史上有记载的第一次大型战争,也是影响中国历史文明进程的重大历史转折之战。本文根据有关记载,汉代画像石以及苗族传说等史料,研究了涿鹿之战的过程。认为黄帝战胜蚩尤的战争是一场以水代兵的... 详细信息

涿鹿之战发生于公元前3000年左右,是我国历史上有记载的第一次大型战争,也是影响中国历史文明进程的重大历史转折之战。本文根据有关记载,汉代画像石以及苗族传说等史料,研究了涿鹿之战的过程。认为黄帝战胜蚩尤的战争是一场以水代兵的水攻战,是掌握了相对先进水利技术的炎黄族战胜以武力见长的蚩尤族的战争。根据有关传说,提出应龙是早期堤堰一类水利工程的化身。涿鹿之战中的“应龙蓄水”为我国历史记载最早的水利工程,进而探讨了我国早期水利工程的起源以及与华夏文明的关系、人类早期的水利活动对文明进程的影响。

关键词：黄帝蚩尤涿鹿之战水攻应龙堤堰文明起源

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VEGFR2基因多态性与左旋多巴疗效和运动障碍的关系

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中南大学学报（医学版） 2015年第11期40卷 1199-1204页

作者：颜元良钱龙方舒龚志成中南大学湘雅医院药学部长沙410013

目的:探讨中国人群中血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)基因rs2305948和rs1870377位点多态性分布与帕金森病(PD)患者使用左旋多巴的疗效和运动障碍的关系,为临床治疗提供理论依据。方法:收... 详细信息

目的:探讨中国人群中血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)基因rs2305948和rs1870377位点多态性分布与帕金森病(PD)患者使用左旋多巴的疗效和运动障碍的关系,为临床治疗提供理论依据。方法:收集69例PD患者,其中32例使用左旋多巴治疗5年内发生运动障碍,为实验组;37例使用左旋多巴治疗8年以上未发生运动障碍,为对照组。采用Taqman MGB探针方法和基因测序,对2组患者的VEGFR2基因rs2305948和rs1870377的多态性进行分析。结果:2组rs2305948和rs1870377位点不同基因多态性间差异无统计学意义(P>0.05)。rs1870377位点AA型的最大左旋多巴使用剂量显著高于AT型和TT型[(565.00±163.55)mg/d vs(396.88±200.39)mg/d,(300.00±80.18)mg/d,P=0.038];且AA型的改良版运动障碍评定量表(Mo d i f i ed A b n o r ma l Invo l u n t a r y Movement Scale,m AIMS)分值显著高于AT型和TT型[(17.00±5.24)vs(8.94±6.53),(7.86±4.45),P=0.026]。结论:VEGFR2基因rs1870377基因多态性与最大左旋多巴使用剂量、m AIMS量表值相关。

关键词：帕金森病左旋多巴 VEGFR2 基因多态性

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清代铜瓦厢改道前的黄河下游河道

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人民黄河 1986年第1期 62-65页

作者：颜元亮水利水电科学研究院

清朝咸丰五年(1855年)黄河于今河南省兰考县北部决口,酿成著名的铜瓦厢改道,结束了七百多年黄河南流的历史。本文就铜瓦厢改道前的黄河情况作了初步研究。

关键词：续行水金鉴十七年道光铜瓦厢黄河清口黄河河道乾隆

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