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KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease

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World Journal of Psychiatry 2024年第3期14卷 445-455页

作者： Qun-Shan Lu Lin Ma Wen-Jing Jiang Xing-Bang Wang Mei Lu Department of Geriatric Medicine Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina key laboratory of cardiovascular proteomics of shandong Province Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and

关键词： Alzheimer's disease Diabetes Insulin resistance KAT7 Dual-specificity tyrosine phosphorylation-regulated kinase-1A HMGN1

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Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy:a meta-analysis

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World Journal of Emergency Medicine 2024年第3期15卷 181-189页

作者： Zeyu Yang Huiruo Liu Dazhou Lu Shengchuan Cao Feng Xu Chuanbao Li Department of Emergency Medicine Qilu Hospital of Shandong UniversityJinan 250012China shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinan 250012China key laboratory of Emergency and Critical Care Medicine of shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinan 250012China shandong key laboratory:Magnetic Field-free Medicine&Functional Imaging(MF) Qilu Hospital of Shandong UniversityJinan 250012China National Medical Products Administration(NMPA)key laboratory for Clinical Research and Evaluation of Innovative Drug Qilu Hospital of Shandong UniversityJinan 250012China

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

关键词： Acute coronary syndrome High-dose Glucose-insulin-potassium treatment Reperfusion therapy Meta-analysis

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Association between prolactin/testosterone ratio and breast cancer in Chinese women

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Chinese Medical Journal 2024年第3期137卷 368-370页

作者： Qian Cai Xiaohan Tian Yuyi Tang Han Cong Jie Liu Song Zhao Rong Ma Jianli Wang Jiang Zhu Department of Geriatric Medicine Qilu Hospital of Shandong UniversityJinanShandong 250012China key laboratory of cardiovascular proteomics of shandong Province Qilu Hospital of Shandong UniversityJinanShandong 250012China Department of Pharmacology School of Basic Medical SciencesShandong UniversityJinanShandong 250012China Department of Breast Surgery General SurgeryQilu Hospital of Shandong UniversityJinanShandong 250012China Department of Thyroid and Breast Surgery Guangdong Second Provincial General HospitalGuangzhouGuangdong 510310China Department of Toxicology and Cancer Biology Collage of MedicineUniversity of KentuckyLexingtonKY 40536USA Department of Immunology School of Basic Medical ScienceShandong UniversityJinanShandong 250012China Department of Gynaecology and Obstetrics Qilu Hospital of Shandong UniversityJinanShandong 250012China

To the Editor:Breast cancer is a prevalent malignant tumor and ranks as the second leading cause of cancer-related deaths globally.^([1])The breast is the target organ of some endocrine hormones,which regulate its growth and development.Aside from estrogen and progesterone,the relationship among prolactin,androgen,and breast cancer has recently garnered increasing attention.

关键词： breast cancer prolactin

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Vaspin alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence

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Emergency and Critical Care Medicine 2024年第1期4卷 4-15页

作者： Haiying Rui Huaxiang Yu Dan Zou Kai Chi Ping Xu Xiaoshuai Song Lulu Liu Xuting Wu Jinxin Wang Li Xue Department of Emergency Medicine and Chest Pain Center Qilu Hospital of Shandong UniversityJinanShandongChina shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityQilu Hospital of Shandong UniversityJinanShandongChina key laboratory of Emergency and Critical Care Medicine of shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinanShandongChina The key laboratory of cardiovascular Remodeling and Function Research Chinese Ministry of EducationChinese Ministry of Health and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu Hospital of Shandong UniversityJinanShandongChina.

Background:Visceral adipose tissue-derived serine protease inhibitor(vaspin),a secretory adipokine,protects against insulin resistance.Recent studies have demonstrated that serum vaspin levels are decreased in patients with coronary artery disease and that vaspin protects against myocardial ischemia-reperfusion injury and atherosclerosis.However,it remains unclear whether vaspin exerts specific effects on pathological cardiac hypertrophy.Methods:An in vivo study was conducted using a cardiac hypertrophy model established by subcutaneous injection of isoproterenol(ISO)in C57BL/6 and vaspin-ko mice.Rapamycin was administered intraperitoneally to mice,for further study.H9c2 cells and neonatal rat ventricular myocytes(NRVMs)were treated with ISO to induce hypertrophy.Human vaspin fusion protein,the proteasome inhibitor MG132,and chloroquine diphosphate were used for further mechanistic studies.Results:Here,we provide the first evidence that vaspin knockdown results in markedly exaggerated cardiac hypertrophy,fibrosis,and cardiomyocyte senescence in mice treated with ISO.Conversely,the administration of exogenous recombinant human vaspin protected NRVMs in vitro against ISO-induced hypertrophy and senescence.Furthermore,vaspin significantly potentiated the ISO-induced decrease in autophagy.Both rapamycin and chloroquine diphosphate regulated autophagy in vivo and in vitro,respectively,and participated in vaspin-mediated cardioprotection.Moreover,the PI3K-AKT-mTOR pathway plays a critical role in vaspin-mediated autophagy in cardiac tissues and NRVMs.Our data showed that vaspin downregulated the p85 and p110 subunits of PI3K by linking p85 and p110 to NEDD4L-mediated ubiquitination degradation.Conclusion:Our results show,for the first time,that vaspin functions as a critical regulator that alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence,providing potential preventive and therapeutic targets for pathological cardiac hypertrophy.

关键词： Autophagic flux Myocardial senescence Pathological cardiac hypertrophy Ubiquitination Vaspin

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Chinese consensus on the diagnosis and treatment of immunoglobulin light-chain cardiac amyloidosis

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Chinese Medical Journal 2024年第2期137卷 127-129页

作者： Kaini Shen Zhuang Tian Yajuan Gao Yining Wang Li Huo Jian Li Yun Zhang Shuyang Zhang On behalf of Chinese Society of Rare Diseases and Rare Diseases Branch of China Research Hospital Association Department of Hematology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Cardiology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Clinical Medicine Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Radiology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Nuclear Medicine Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear MedicineState Key Laboratory of Complex Severe and Rare DiseasesCenter for Rare Diseases ResearchPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Cardiology The Key Laboratory of Cardiovascular Remodeling and Function ResearchChinese Ministry of EducationChinese National Health Commission and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250012China cardiovascular Disease Research Center of shandong First Medical University Central Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250013China 不详

Epidemiology of Amyloid Light-Chain Cardiac Amyloidosis(AL-CA)The annual incidence of amyloid light-chain(AL)amyloidosis is 3-5/million,and the incidence in men is slightly higher than that in women.Approximately,70%o... 详细信息

关键词： amyloid cardiac diagnosis

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Si-Miao-Yong-An Decoction alleviates thromboangiitis obliterans by regulating miR-548j-5p/IL-17A signaling pathway

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Chinese Journal of Natural Medicines 2024年第6期22卷 541-553页

作者： CHU Chu SUN Shangwen ZHANG Zhen WU Qi LI Haoyang LIANG Gang MIAO Xiuming JIANG Haiqiang GAO Yan ZHANG Yunhong WANG Bin LI Xia Innovative Institute of Chinese Medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinan 250355China National key laboratory for Innovation and Transformation of Luobing Theory The Key Laboratory of Cardiovascular Remod-eling and Function ResearchChinese Ministry of EducationChinese National Health Commission and Chinese Academy of Medical SciencesDepartment of CardiologyQilu Hospital of Shandong UniversityJinan 250012China School of Clinical and Basic Medical Sciences Shandong First Medical University&Shandong Academy of Medical SciencesJinan 271016China Affiliated Hospital of shandong University of Traditional Chinese Medicine Jinan 250014China International Business School Tianjin Foreign Studies UniversityTianjin 300204China Institute of Pharmaceutical Research Shandong University of Traditional Chinese MedicineJinan 250355China

Thromboangiitis obliterans(TAO)is a rare,chronic,progressive,and segmental inflammatory disease characterized by a high rate of amputation,significantly compromising the quality of life of patients.Si-Miao-Yong-An decoction(SMYA),a tradition-al prescription,exhibits anti-inflammatory,anti-thrombotic,and various other pharmacological properties.Clinically,it was fully proved to be effective for TAO therapy,but the specific therapeutic effect of SMYA on TAO has been unknown.Thus,deep unveiling the mechanism of SMYA in TAO for identifying clinical therapeutic targets is extremely important.In this study,we observed elev-ated levels of IL-17A in the peripheral blood mononuclear cells(PBMCs)of TAO patients,whereas the expression of miR-548j-5p was significantly decreased.A negative correlation between the levels of miR-548j-5p and IL-17A was also demonstrated.In vitro ex-periments showed that overexpression of miR-548j-5p led to a decrease in IL-17A levels,whereas downregulation of miR-548j-5p showed the opposite effect.Using a dual luciferase assay,we confirmed that miR-548j-5p directly targets IL-17A.Furthermore,serum containing SMYA effectively decreased IL-17A levels by increasing the expression of miR-548j-5p.More importantly,the results of in vivo tests indicated that SMYA mitigated the development of TAO by inhibiting IL-17A through the upregulation of miR-548j-5p in vascular tissues.In conclusion,SMYA significantly enhances the expression of miR-548j-5p,thereby reducing the levels of the target gene IL-17A and alleviating TAO.Our research not only identifies novel targets and pathways for the clinical diagnosis and treatment of TAO but also advances the innovation in traditional Chinese medicine through the elucidation of the SMYA/miR-548j-5p/IL-17A regulatory axis in the pathogenesis of TAO.

关键词： Thromboangiitis obliterans IL-17A Inflammation miR-548j-5p Si-Miao-Yong-An Decoction

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An unusual anterior mitral leaflet perforation in a patient with no infective endocarditis:a case report

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Emergency and Critical Care Medicine 2024年第1期4卷 39-41页

作者： Kaiming Wei Yu Yao Chuanzhen Liu Yuan Cao Department of cardiovascular Surgery Qilu Hospital of Shandong UniversityJinanShandongChina Department of Emergency Medicine Qilu Hospital of Shandong UniversityJinanShandongChina National key laboratory for Innovation and Transformation of Luobing Theory The Key Laboratory of Cardiovascular Remodeling and Function ResearchChinese Ministry of EducationChinese National Health Commission and Chinese Academy of Medical SciencesDepartment of CardiologyQilu Hospital of Shandong UniversityJinanShandongChina.

Background:Mitral valve perforation refers to the occurrence of cracks or openings in the structure of the mitral valve,allowing blood to escape through these gaps.Typically,this is caused by infective endocarditis and the most common site is the anterior leaflet.However,it is crucial to explore other potential causes of valve damage,particularly when conventional risk factors are not apparent.Case presentation:We present a case of a middle-aged male patient who developed mitral valve perforation because of aortic valve regurgitation in the absence of infective endocarditis.Conclusion:Exploring such rare cases contributes to a deeper understanding of valvular diseases and enhances clinical decision making for effective management.

关键词： Anterior mitral leaflet Aortic valve Case report Perforation Prolapse Regurgitation

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Potential impact of specific therapy on pregnant women with pulmonary arterial hypertension without cardiac shunt:a descriptive study in northern China

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Emergency and Critical Care Medicine 2024年第2期4卷 60-66页

作者： Weida Lu Min Li Fuqing Ji Hua Feng Guo Li Qiushang Ji Hongyu Zhang Xiaopei Cui Department of Geriatric Medicine&shandong key laboratory cardiovascular proteomics Qilu Hospital of Shandong UniversityJinanShandongChina Intensive Care Unit of Cardiac Surgery Shandong Provincial Qianfoshan Hospitalthe First Hospital Affiliated with Shandong First Medical UniversityAffiliated Hospital of Shandong UniversityJinanShandongChina Department of Cardiology Linyi Central HospitalLinyiShandongChina Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina Department of Pulmonary and Critical Care Medicine the Affiliated Hospital of Qingdao UniversityQingdaoShandongChina Department of Cardiology Qilu Hospital of Shandong UniversityJinanShandongChina

Background:Pregnancy in women with pulmonary arterial hypertension(PAH)is a fatal condition,despite the effectiveness of PAH-specific therapies.The coverage status and effect of specific therapies in pregnant patients with PAH without cardiac shunts in China remain unclear.To investigate this issue,we conducted a multicenter retrospective study in northern China.Methods:The study included 85 patients who were admitted to 4 clinical centers in shandong Province between October 2010 and August 2020.Maternal endpoint events included(1)maternal death and/or(2)major adverse cardiac events,both occurring during pregnancy or within 6 weeks postpartum.Results:Although the overall mortality rate was encouraging(11.8%),the number of patients receiving PAH-specific therapies was extremely low(28.2%).Moreover,only 15.3%of patients received adequate duration of PAH-specific therapy(≥4 weeks)before delivery,and this subgroup showed the lowest major adverse cardiac events rate(7.7%)compared with that in the untreated(19.7%)and short-time treated groups(<4 weeks;54.5%).Conclusion:Pregnant patients with PAH without cardiac shunts face significantly increased mortality risks.Short-term PAH-specific therapy does not guarantee favorable maternal outcomes.Prepregnancy screening,early identification,and timely intervention are expected to improve maternal outcomes in pregnant women with PAH.

关键词： Major adverse cardiac events Maternal mortality Pregnancy outcome Pulmonary arterial hypertension Specific therapy

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Comparative proteomics reveals the response and adaptation mechanisms of white Hypsizygus marmoreus against the biological stress caused by Penicillium

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Food Science and Human Wellness 2024年第3期13卷 1645-1661页

作者： Xiuqing Yang Sizhu Li Xiaohang Li Chenxiao Zhang Meijie Liu Lizhong Guo Lin Liu Hao Yu shandong Provincial key laboratory of Applied Mycology School of Life SciencesQingdao Agricultural UniversityQingdao 266109China

White Hypsizygus marmoreus is a popular edible mushroom.Its mycelium is easy to be contaminated by Penicillium,which leads to a decrease in its quality and yield.Penicillium could compete for limited space and nutrients through rapid growth and produce a variety of harmful gases,such as benzene,aldehydes,phenols,etc.,to inhibit the growth of H.marmoreus mycelium.A series of changes occurred in H.marmoreus proteome after contamination when detected by the label-free tandem mass spectrometry(MS/MS)technique.Some proteins with up-regulated expression worked together to participate in some processes,such as the non-toxic transformation of harmful gases,glutathione metabolism,histone modification,nucleotide excision repair,clearing misfolded proteins,and synthesizing glutamine,which were mainly used in response to biological stress.The proteins with down-regulated expression are mainly related to the processes of ribosome function,protein processing,spliceosome,carbon metabolism,glycolysis,and gluconeogenesis.The reduction in the function of these proteins affected the production of the cell components,which might be an adjustment to adapt to growth retardation.This study further enhanced the understanding of the biological stress response and the growth restriction adaptation mechanisms in edible fungi.It also provided a theoretical basis for protein function exploration and edible mushroom food safety research.

关键词： Hypsizygus marmoreus Penicillium proteomics Biological stress response Adaptation

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Degradation and biocompatibility of one-step electrodeposited magnesium thioctic acid/magnesium hydroxide hybrid coatings on ZE21B alloys for cardiovascular stents

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Journal of Magnesium and Alloys 2024年第1期12卷 120-138页

作者： Zhao-Qi Zhang Bing-Zhi Li Pei-Duo Tong Shao-Kang Guan Li Wang Zheng-Hui Qiu Cun-Guo Lin Rong-Chang Zeng School of Material Science and Engineering&Henan key laboratory of Advanced Magnesium Alloy&key laboratory of Materials Processing and Mold Technology(Ministry of Education) Zhengzhou University100 Science RoadZhengzhou 450001China State key laboratory for Marine Corrosion and Protection Luoyang Ship Material Research InstituteQingdao 266101China Corrosion laboratory for Light Metals College of Material Science and EngineeringShandong University of Science and TechnologyQingdao 266590China

Constructing a functional hybrid coating appears to be a promising strategy for addressing the poor corrosion resistance and insufficient endothelialization of Mg-based stents.Nevertheless,the steps for preparing composite coatings are usually complicated and time-consuming.Herein,a novel composite coating,composed of bioactive magnesium thioctic acid(MTA)layer formed by deposition and corrosion-resistant magnesium hydroxide(Mg(OH)_(2))layer grown in situ,is simply fabricated on ZE21B alloys via one-step electrodeposition.Scanning electron microscopy(SEM)shows that the electrodeposited coating has a compact and uniform structure.And the high adhesion of the MTA/Mg(OH)_(2)hybrid coating is also confirmed by the micro-scratch test.Electrochemical test,scanning kelvin probe(SKP),and hydrogen evolution measurement indicate that the hybrid coating effectively reduces the degradation rate of Mg substrates.Haemocompatibility experiment and cell culture trial detect that the composite coating is of fine biocompatibility.Finally,the preparation mechanism of MTA/Mg(OH)_(2)hybrid coatings is discussed and proposed.This coating shows a great potential application for cardiovascular stents.

关键词： Magnesium alloy Corrosion resistance Hybrid coating Endothelialization Biocompatibility

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