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Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway

Genes & Diseases 2024年第2期11卷 747-759页

作者： Tao Wang Xinzhe Chen Kai Wang Jie Ju Xue Yu Wanpeng Yu Cuiyun Liu Yin Wang Institute for Translational medicine The Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdaoShandong 266023China college of medicine Qingdao UniversityQingdaoShandong 266023China

In the mammalian heart,cardiomyocytes are forced to withdraw from the cell cycle shortly after birth,limiting the ability of the heart to regenerate and *** development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac *** the continuous development of genetic lineage tracking technology,it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic,juvenile,and adult stages of cardiogenesis,but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial *** implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury,which offers hope for the clinical treatment of myocardial ***,the regeneration frequency and source of cardiomyocytes are still low,and the mechanism of regulating cardiomyocyte proliferation remains further *** is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart ***,we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart *** addition,myocardial transcription factors,non-coding RNAs,cyclins,and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte ***,awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

关键词： Cardiac regeneration Cell cycle re-enter Myocardial infarction Pre-existing cardiomyocyte proliferation Regenerative therapy of cardiovascular diseases

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Molecular Mechanism of Polysaccharides Extracted from Chinese medicine Targeting Gut Microbiota for Promoting Health

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Chinese Journal of Integrative medicine 2024年第2期30卷 171-180页

作者： ZHAO Wen-xiao WANG Tong ZHANG Ya-nan CHEN Qian WANG Yuan XING Yan-qing ZHENG Jun DUAN Chen-chen CHEN Lijun ZHAO Hai-jun WANG Shijun School of Nursing Shandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJi'nan(250355)China shandong Co-innovation Center of Classic Traditional Chinese medicine Formula Shandong University of Traditional Chinese MedicineJi'nan(250355)China college of Traditional Chinese medicine Shandong University of Traditional Chinese MedicineJinan(250355)China

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity,type 2 diabetes mellitus,heart failure,and non-alcoholic fatty liver *** extracted from Chinese medicine(CM)can not only alleviate pathological status but also promote health by anti-inflammatory,regulating immunity,lowering blood glucose and lipids,anti-cancer,and *** alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides *** addition,they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut *** review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics forpromoting health.

关键词： Chinese medicine polysaccharides gut microbiota short-chain fatty acids lipopolysaccharides gut-organaxis synergistic actions

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Biological Evaluation of Lysionotin:a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma

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Chinese Journal of Integrative medicine 2024年第9期30卷 826-834页

作者： SHAO Xin-xin CHEN Cong LIU Jie LI Qing-jun HE Shan QI Xiang-hua FU Xian-jun WANG Zhen-guo The First Clinical college of medicine Shandong University of Traditional Chinese MedicineJinan250355China Institute for Literature and Culture of Chinese medicine Shandong University of Traditional Chinese MedicineJinan250355China Key Laboratory of Classical Theory of Traditional Chinese medicine Ministry of EducationShandong University of Traditional Chinese MedicineJinan250355China college of Pharmacy Shandong University of Traditional Chinese MedicineJinan250355China Experimental Center Shandong University of Traditional Chinese MedicineJinan250355China Neurology Department Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan250014China Marine Traditional Chinese medicine Research Center Qingdao Academy of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineQingdao266114Shandong ProvinceChina

Objective:To explore the potential mechanism of lysionotin in treating ***:First,target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of *** binding between 5-lipoxygenase(5-LO)and lysionotin was detected by surface plasmon resonance(SPR)and molecular docking,and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis,***,the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry(LC-MS/MS).The protein expression,intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot,flow cytometry and fluorescence labeling,***:Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO,a key enzyme involved in the arachidonic acid metabolism pathway,to inhibit the proliferation of *** docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds,forming bonds with His600,Gln557,Asn554,and *** analysis further confirmed the interaction between 5-LO and ***,enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50%inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58µmol/L,respectively,and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid(P<0.05),and moreover,the LC-MS/MS results indicated that lysionotin can enter glioma cells well(P<0.01)and inhibit their *** blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO(P<0.05)and downstream leukotriene B4 receptor(P<0.01).In addition,the results showed that lysionotin affected intracellular calcium ion concentration by inh

关键词： 5-lipoxygenase inhibitor lysionotin 5-lipoxygenase leukotriene B4 calcium ion cytoskeleton

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Beware of the serious harm of veterinary drug poisoning:a case report

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World Journal of Emergency medicine 2024年第2期15卷 153-155页

作者： Ping Dai Jin Sun Tongyue Zhang Zhiqiang Zhou Zixi Wen Tianzi Jian Aerbusili Genjiafu Baotian Kan Xiangdong Jian Department of Poisoning and Occupational Diseases Emergency MedicineQilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012China Emergency Department Affiliated the Jianhu Clinical Medical College of Yangzhou UniversityYancheng 224700China Department of Occupational and Environmental Health School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China School of Nursing and Rehabilitation Cheeloo College of MedicineShandong UniversityNursing Theory&Practice Innovation Research Center of Shandong UniversityJinan 250012China Department of Geriatric medicine Qilu HospitalNursing Theory Innovation and Research Center of Shandong UniversityCheeloo College of MedicineShandong UniversityJinan 250012China

Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of *** drug poisoning in humans is relatively rare both in China and the rest of the ***,we report a case of death from veterinary drug poisoning from ***-closantel is a broad-spectrum antiparasitic drug,which has high efficacy against a variety of trematodes and nematodes.

关键词： drug drugs diseases

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Chemotherapy induces breast cancer stem cell enrichment through repression of glutathione S-transferase Mu

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Genes & Diseases 2024年第2期11卷 528-531页

作者： Jing He Yiran Yu Yilin He Jie He Guangyu Ji Haiquan Lu The Second Hospital and Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinanShandong 250012China Department of Nursing The First Affiliated Hospital of Shandong First Medical UniversityJinanShandong 250014China School of medicine Xinjiang Medical UniversityUrumqiXinjiang 830054China School of medicine Binzhou Medical UniversityYantaiShandong 264003China Oncology Department Jinan Zhangqiu District People's HospitalJinanShandong 250200China Key Laboratory for Experimental Teratology of the Ministry of Education Cheeloo College of MedicineShandong UniversityJinanShandong 250012China Center for Reproductive medicine Shandong UniversityJinanShandong 250012China

Triple-negative breast cancer(TNBC)has aggressive characteristics as exemplified by the high risk of recurrence,metastasis,and patient mortality.1 Cytotoxic chemotherapy may reduce tumor burden initially,but leave behind chemo-resistant breast cancer stem cells(BCSCs)that lead to tumor recurrence and metastasis.2 Chemotherapy induces BCsC enrichment through the activation of glutathione biosynthesis pathways,which increases intracellular glutathione levels and specifies the BCSC phenotype through complicated downstream signaling pathways.3 Glutathione S-transferases(GSTs),a superfamily(which contains seven cytosolic classes:Alpha,Kappa,Mu,Omega,Pi,Theta,and Zeta,and one microsomal class MGSTs)of phase Il enzymes that catalyze the conjugation of glutathione with electrophilic compounds,play a critical role in detoxification and chemotherapy resistance of cancer ***,the role of GSTs in the regulation of BCSCs is largely elusive.

关键词： chemotherapy breast metastasis

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Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

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Animal Models and Experimental medicine 2024年第2期7卷 114-126页

作者： Xuyu Song Ying Liu Siyi Chen Lei Zhang Huijie Zhang Xianhui Shen Hang Du Rong Sun Orthopaedic trauma surgery The Second Hospital of Shandong UniversityJinanShandongChina Academy of Traditional Chinese medicine Tianjin University of Traditional Chinese MedicineTianjinChina Department of Traditional Chinese medicine The Second Hospital of Shandong UniversityJinanShandongChina college of pharmacy Shandong University of Traditional Chinese MedicineJinanShandongChina The Second Clinical college of shandong university Shandong UniversityJinanShandongChina Advanced Medical Research Institute Shandong UniversityJinanShandongChina The Second Hospital of shandong university JinanShandongChina

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging *** pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same ***,researchers are interested in studying KOA and require appropriate animal models for basic *** herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget *** potential benefits in the treatment of KOA continue to attract ***:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal *** will help researchers make informed decisions when choosing an animal ***:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to ***:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal ***:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

关键词： animal models knee osteoarthritis system review traditional Chinese medicine

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Associations between the use of red yeast rice preparations and adverse health outcomes:An umbrella review of meta-analyses of randomized controlled trials

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Journal of Integrative medicine 2024年第2期22卷 126-136页

作者： Zhen-yu Ma Shu-ping Yang Ying Li Tian-tian Xu Ya-lin Yang Hui-yong Yang Heng-bing Li Le-jin Zhou Yong Diao Su-yun Li School of medicine Huaqiao UniversityQuanzhou 362021Fujian ProvinceChina college of Traditional Chinese medicine Shandong University of Traditional Chinese MedicineJinan 250355Shandong ProvinceChina Second Clinical Medical college Nanjing Medical UniversityNanjing 211166Jiangsu ProvinceChina

Background:Red yeast rice(RYR),a natural lipid-lowering agent,is widely used in clinical ***,the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results,and the credibility of the evidence has not been ***:This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health *** strategy:Seven literature databases were searched from inception to May 5,2023,using medical subject headings and free-text terms(e.g.,“red yeast rice,”“Xuezhikang,”and“Zhibitai”).Inclusion criteria:Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this *** extraction and analysis:Two researchers independently extracted data using a standardized data collection table;any disagreements were resolved by consulting a third *** on the participant,intervention,comparator and outcome(PICO)framework in each eligible meta-analysis,a series of unique associations between the use of RYR preparations and adverse health outcomes were *** associations’effect estimates were re-evaluated using random-effect ***:Fifteen meta-analyses,comprising 186(164 unique)randomized controlled trials,were *** on A Mea Surement Tool to Assess Systematic Reviews version 2,3(20%)and 12(80%)of these meta-analyses had low and critically low confidence,respectively.A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible *** on the random-effect models,10(16.4%)associations indicated a significant protective effect of RYR preparations against adverse health outcomes,while 5(8.2%)indicated an increased risk of adverse health outcomes related to uric acid,alanine transaminase and aspartate trans

关键词： Red yeast rice Safety Adverse health outcomes Umbrella review Meta-analysis Systematic review

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Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

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Animal Models and Experimental medicine 2024年第3期7卷 259-274页

作者： Huirong Xu Meiyue Dong Ruikun Du Chengcheng Zhang Zinuo Chen Guangyu Tian Qinghua Cui Kejian Li college of Traditional Chinese medicine Shandong University of Traditional Chinese MedicineJinanChina Innovative Institute of Chinese medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinanChina Qingdao Academy of Chinese Medical Sciences Shandong University of Traditional Chinese MedicineQingdaoChina college of Pharmacy Shandong University of Traditional Chinese MedicineJinanChina

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating *** present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network ***:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)*** intersection of blood component-related targets and disease-related targets was determined using Venny ***-protein interaction networks were constructed using the STRING *** Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway ***,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral ***:Fifteen compounds and 124 targets linked to viral pneumonia were detected in *** these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant *** vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 ***,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and ***:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

关键词： network pharmacology pharmacodynamical material basis serum pharmacochemistry viral pneumonia YangshenDingzhi granules

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The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

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Neural Regeneration Research 2024年第5期19卷 1084-1091页

作者： Yijing Zhao Tong Li Zige Jiang Chengcheng Gai Shuwen Yu Danqing Xin Tingting Li Dexiang Liu Zhen Wang Department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Neurosurgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina Department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao UniversityJinanShandong ProvinceChina

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal ***,the precise mechanism underlying the role of H2S in this situation remains *** this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal *** also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ***,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these *** findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

关键词： chemokine(C-X-C motif)ligand 11 cystathionineβsynthase H2S hypoxic ischemic brain injury inflammation L-cysteine lipopolysaccharide microglia miR-9-5p neuroprotection

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Inhalable metal–organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2281-2297页

作者： Chongzheng Yan Ying Liu Guozhi Zhao Huatian Yang Huaiyou Lv Genju Li Yuhan Li Yaqing Fu Fengqin Sun Yafei Feng Yizhe Li Zhongxi Zhao Department of Pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China Key university Laboratory of Pharmaceutics&Drug Delivery Systems of shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Cuproptosis shows enormous application prospects in lung metastasis ***,the glycolysis,Cu^(+)efflux mechanisms,and insufficient lung drug accumulation severely restrict cuproptosis ***,an inhalable poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)(OPDEA)-coated copper-based metal–organic framework encapsulating pyruvate dehydrogenase kinase 1 siRNA(siPDK)is constructed for mediating cuproptosis and subsequently promoting lung metastasis immunotherapy,namely *** inhalation,OMP shows highly efficient lung accumulation and long-term retention,ascribing to the OPDEA-mediated pulmonary mucosa *** tumor cells,OMP is degraded to release Cu2+under acidic condition,which will be reduced to toxic Cu^(+)to induce cuproptosis under glutathione(GSH)***,siPDK released from OMP inhibits intracellular glycolysis and adenosine-5ʹ-triphosphate(ATP)production,then blocking the Cu^(+)efflux protein ATP7B,thereby rendering tumor cells more sensitive to OMP-mediated ***,OMP-mediated cuproptosis triggers immunogenic cell death(ICD)to promote dendritic cells(DCs)maturation and CD8^(+)T cells ***,OMP-induced cuproptosis up-regulates membrane-associated programmed cell death-ligand 1(PD-L1)expression and induces soluble PD-L1 secretion,and thus synergizes with anti-PD-L1 antibodies(aPD-L1)to reprogram immunosuppressive tumor microenvironment,finally yielding improved immunotherapy ***,OMP may serve as an efficient inhalable nanoplatform and afford preferable efficacy against lung metastasis through inducing cuproptosis and combining with aPD-L1.

关键词： Cuproptosis Immunogenic cell death PD-L1 checkpoint blockade Copper-based metal-organic framework Immunotherapy Tumor microenvironment Transmucosal deliveryLung metastasis

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