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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military medical research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor *** the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment *** evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully *** Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of *** investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo *** signaling pathway components were evaluated using multi-omics *** were performed to elucidate the regulation of lipid metabolic reprogramming of *** We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic ***,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain *** Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of ***2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

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Pan-cancer immunogenic death analysis identifies key roles of CXCR3 and CCL18 in hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 568-570页

作者： Jia Guo Xin Sun Guowei Pan Ce Li Xin He Xiaofang Che Zan Teng Xiujuan Qu Yunpeng Liu Bowen Yang Department of medical Oncology Provincial Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning ProvinceLiaoning Provincial Clinical Research Center for CancerClinical Cancer Research Center of ShenyangThe First Hospital of China Medical UniversityShenyangLiaoning 110001China research center for Universal Health School of Public HealthChina Medical UniversityShenyangLiaoning 110122China

Immunogenic death is a form of programmed cell death that is common in the development and progression of ***,its impact on tumor progression differs depending on the location of the ***,it also plays an important role in antitumor immunity because the process of immunogenic death can release substances that activate immunity.1 Therefore,in this study,the key mechanism of mediating immunogenic death in hepatocellular carcinoma(HCC)was found from the excavation of the immunogenic death characteristics of pan-cancer and the in-depth investigation of its effects on different tumor types(Fig.1A).

关键词： death CXCR3 immunity

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Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke

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research 2024年第1期2023卷 369-387页

作者： Hongfei Ge Tengyuan Zhou Chao Zhang Yupeng Cun Weixiang Chen Yang Yang Qian Zhang Huanhuan Li Jun Zhong Xuyang Zhang Hua Feng Rong Hu Department of Neurosurgery and Key laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina medical research center Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Pediatric research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChildren’s Hospital of Chongqing Medical University400014 ChongqingChina

Cell replacement therapy using neural progenitor cells(NPCs)has been shown to be an effective treatment for ischemic ***,the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after *** acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a(ASIC1a),a subunit of proton-gated cation channels following ischemic ***,the role of ASIC1a in NPCs post-ischemia remains ***,our results indicated that ASIC1a was expressed in NPCs with channel functionality,which could be activated by extracellular *** evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation,which could be primarily reversed by pharmacological or genetic disruption of *** vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke.

关键词： ASIC1a homeostasis inhibited

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Association of acute glycemic parameters at admission with cardiovascular mortality in the oldest old with acute myocardial infarction

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Journal of Geriatric Cardiology 2024年第3期21卷 349-358页

作者： Hui-Hui LIU Meng ZHANG Yuan-Lin GUO Cheng-Gang ZHU Na-Qiong WU Ying GAO Rui-Xia XU Jie QIAN Ke-Fei DOU Jian-Jun LI Cardiometabolic center State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVES Stress-related glycemic indicators,including admission blood glucose(ABG),stress-hyperglycemia ratio(SHR),and glycemic gap(GG),have been associated with worse outcomes after acute myocardial infarction(AMI).However,data regarding their prognostic value in the oldest old with AMI are ***,this study aimed to investigate the association of stress-related glycemic indicators with short-and long-term cardiovascular mortality(CVM)in the oldest old(≥80 years)with *** In this prospective study,a total of 933 consecutive old patients with AMI admitted to FuWai hospital(Beijing,China)were *** admission,ABG,SHR,and GG were assessed and all participants were classified according to their ***-Meier,restricted cubic splines(RCS),and multivariate Cox regression analyses were performed to evaluate the association between these glycemic indicators and CVM within 30 days and long-term *** During an average of 1954 patient-years of follow-up,a total of 250 cardiovascular deaths were ***-Meier analyses showed the lowest CVM in quartile 1 of ABG and in quartile 2 of SHR and *** adjusting for potential covariates,patients in quartile 4 of ABG,SHR,and GG had a respective 1.67-fold(95%CI:1.03-2.69;P=0.036),1.80-fold(95%CI:1.16-2.79;P=0.009),and 1.78-fold(95%CI:1.14-2.79;P=0.011)higher risk of long-term CVM risk compared to those in the reference groups(quartile 1 of ABG and quartile 2 of SHR and GG).Furthermore,RCS suggested a J-shaped relationship of ABG and a Ushaped association of SHR and GG with long-term ***,we observed similar associations of these acute glycemic parameters with 30-day *** Our data first indicated that SHR and GG consistently had a U-shaped association with both 30-day and longterm CVM among the oldest old with AMI,suggesting that they may be useful for risk stratification in this special population.

关键词： admitted infarction shaped

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Regulations of m^(6)A and other RNA modifications and their roles in cancer

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Frontiers of Medicine 2024年第4期18卷 622-648页

作者： Xin-Hui Chen Kun-Xiong Guo Jing Li Shu-Hui Xu Huifang Zhu Guang-Rong Yan Biomedicine research center Guangdong Provincial Key Laboratory of Major Obstetric DiseaseGuangdong Provincial Clinical Research Center for Obstetrics and GynecologyState Key Laboratory of Respiratory Diseasethe Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhou510150China

RNA modification is an essential component of the epitranscriptome,regulating RNA metabolism and cellular *** types of RNA modifications have been identified to date;they include N^(6)-methyladenosine(m^(6)A),N^(1)-methyladenosine(m1A),5-methylcytosine(m5C),N^(7)-methylguanosine(m^(7)G),N^(6),2′-O-dimethyladenosine(m^(6)Am),N4-acetylcytidine(ac^(4)C),*** modifications,mediated by regulators including writers,erasers,and readers,are associated with carcinogenesis,tumor microenvironment,metabolic reprogramming,immunosuppression,immunotherapy,chemotherapy,etc.A novel perspective indicates that regulatory subunits and post-translational modifications(PTMs)are involved in the regulation of writer,eraser,and reader functions in mediating RNA modifications,tumorigenesis,and anticancer *** this review,we summarize the advances made in the knowledge of different RNA modifications(especially m^(6)A)and focus on RNA modification regulators with functions modulated by a series of factors in cancer,including regulatory subunits(proteins,noncoding RNA or peptides encoded by long noncoding RNA)and PTMs(acetylation,SUMOylation,lactylation,phosphorylation,etc.).We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer ***,inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.

关键词： RNA modification writers erasers readers regulatory subunits PTMs cancer

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Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients

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Journal of Geriatric Cardiology 2024年第2期21卷 211-218页

作者： Luo-Xi XIAO Zi-Yu WANG Jiang-Tao LI Hai-Mei WANG Yi-Ming HAO Pan ZHOU Yu-Lin HUANG Qiu-Ju DENG Yong-Chen HAO Na YANG Li-Zhen HAN Zhao YANG Ping-Ping JIA Yue QI Jing LIU center for clinical and Epidemiologic research Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLung and Blood Vessel DiseasesBeijing Municipal Key Laboratory of Clinical EpidemiologyBeijingChina

BACKGROUND Hypertension usually clusters with multiple ***,the association between cardiometabolic multimorbidity(CMM)and mortality in hypertensive patients is *** study aimed to investigate the association between CMM and all-cause and cardiovascular disease(CVD)mortality in Chinese patients with *** The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors(CONSIDER),which comprised 5006 participants aged 19–91 *** was defined as the presence of one or more of the following morbidities:diabetes mellitus,dyslipidemia,chronic kidney disease,coronary heart disease,and *** proportional hazard models were used to calculate the hazard ratios(HR)with 95%CI to determine the association between the number of CMMs and both all-cause and CVD *** Among 5006 participants[mean age:58.6±10.4 years,50%women(2509 participants)],76.4%of participants had at least one *** mortality rate was 4.57,4.76,8.48,and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one,two,and three or more morbidities,*** the fully adjusted model,hypertensive participants with two cardiometabolic diseases(HR=1.52,95%CI:1.09–2.13)and those with three or more cardiometabolic diseases(HR=2.44,95%CI:1.71–3.48)had a significantly elevated risk of all-cause *** findings were similar for CVD mortality but with a greater increase in risk *** In this study,three-fourths of hypertensive patients had *** with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients,suggesting more intensive treatment and control in this high-risk patient group.

关键词： hypertensive patients morbidity

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Gastric cancer secreted miR 214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

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Oncology research 2024年第3期32卷 489-502页

作者： WEIXUE WANG TONGTONG WANG YAN ZHANG TING DENG HAIYANG ZHANG YI BA Department of GI medical Oncology Tanjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerTianjin Key Iaboratory of Digestive CancerKey Laboratory of Cancer Prevention and TherapyTianjin300060China

Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell *** is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis ***,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported *** exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been ***,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of *** conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

关键词： Cellular ferroptosis Exosome Tyrosine kinase inhibitor Gastrointestinal tumors miRNA

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clinical outcomes of second-line chemotherapy in patients with advanced pancreatic adenocarcinoma:a real-world study

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Cancer Biology & Medicine 2024年第9期21卷 799-812页

作者： Yuxiao Liu Xiaofan Guo Peijun Xu Yuning Song Jing Huang Xingyun Chen Wenbo Zhu Jihui Hao Song Gao Department of Pancreatic Cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China

Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition,the optimal second-line chemotherapy regimen has not been *** study aimed to compare the effectiveness of different types of second-line chemotherapy for ***:Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective *** primary and secondary endpoints were overall survival(OS)and progression-free survival(PFS),***:Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment,*** and clinical features,except age and liver metastasis,were comparable between the two groups(P<0.05).The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy,respectively(HR=1.244,95%CI=1.090–1.419;P<0.001).The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care,respectively(HR=0.766,95%CI=0.677–0.867;P<0.001).The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination ***:A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.

关键词： Second-line chemotherapy advanced pancreatic adenocarcinoma 5-fluorouracil gemcitabine real-world study

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Rapid and sensitive detection of urinary KIM-1 using fully printed photonic crystal microarrays

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Nano research 2024年第5期17卷 4329-4337页

作者： Yang Liu Xuwei He Zewei Lian Qian Guo Jimei Chi Xiaoxue Lin Liyue Zhang Zheng Liu Yingyuan Liu Meng Su Keyu Wang Qiangguo Ao Qingli Cheng Department of Nephrology The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China Chinese PLA medical School Beijing 100853China Key laboratory of Green Printing CAS Research/Education Center for Excellence in Molecular SciencesBeijing Engineering Research Center of Nanomaterials for Green Printing TechnologyBeijing National Laboratory for Molecular Sciences(BNLMS)Institute of ChemistryChinese Academy of Sciences(ICCAS)Beijing 100190China Department of Rheumatology and Immunology Peking University International HospitalBeijing 102206China Department of clinical laboratory The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China

Urinary kidney injury molecule 1(uKIM-1)serves as a reliable marker for the early diagnosis of acute kidney injury(AKI).The rapid and facile detection of changes in uKIM-1 is essential for early AKI diagnosis,ultimately improving the prognosis of *** this study,we developed a fully printed photonic crystal-integrated microarray with photonic crystal-enhanced fluorescence properties,which can detect uKIM-1 levels at the *** confirmed its efficacy in the early diagnosis of AKI using clinical urine *** quantitative detection of uKIM-1 was achieved within 10 *** lowest limit of detection is 8.75 pg·mL^(-1) with an accuracy of 94.2%.The diagnostic efficacy was validated using 86 clinical urine samples,highlighting the high sensitivity and stability of the photonic crystal ***,a facile and reliable immunoassay was designed and prepared for the rapid quantitative detection of uKIM-1,which is crucial for the early identification and convenient detection of AKI in hospital or community ***,convenient,cost-effective,and long-term monitoring of changes in uKIM-1 levels can assist clinicians in making timely adjustments to treatment regimens,preventing the transition from AKI to chronic kidney disease(CKD),improving the quality of life of patients with AKI,and reducing healthcare *** highlights the advantages of utilizing urine samples as a noninvasive and easily accessible medium for early detection and monitoring of kidney-related conditions.

关键词： photonic crystal point-of-care testing urine kidney injury molecule-1(KIM-1) acute kidney injury

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Molecular glue triggers degradation of PHGDH by enhancing the interaction between DDB1 and PHGDH

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4001-4013页

作者： Ziqi Huang Kun Zhang Yurui Jiang Mengmeng Wang Mei Li Yuda Guo Ruolin Gao Ning Li Chenyang Wang Jia Chen Jiefu Wang Ning Liu Xiang Liu Shuangwei Liu Mingming Wei Cheng Yang Guang Yang The State Key laboratory of Medicinal Chemical Biology College of Life SciencesCollege of PharmacyNankai UniversityTianjin 300071China Tianjin medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China

Cancer stem cells(CSCs)play a pivotal role in tumor initiation,proliferation,metastasis,drug resistance,and ***,targeting CSCs has emerged as a promising avenue for cancer ***,3-phosphoglycerate dehydrogenase(PHGDH)has been identified as being intricately associated with the regulation of numerous cancer stem ***,reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are *** this study,the novel“molecular glue”LXH-3-71 was identified,and it robustly induced degradation of PHGDH,thereby modulating the stemness of colorectal cancer cells(CRCs)both in vitro and in ***,LXH-3-71 was observed to form a dynamic chimera,between PHGDH and the DDB1-CRL E3 *** insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH ***,compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase,facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation.

关键词： Molecular glue Targeted protein degradation PHGDH Cancer stem cells PROTACs

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