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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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Protein lysine crotonylation in cellular processions and disease associations

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Genes & Diseases 2024年第5期11卷 219-235页

作者： Hongling Zhao Yang Han Pingkun Zhou Hua Guan Shanshan Gao Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation MedicineBeijing 100850China

Protein lysine crotonylation(Kcr)is one conserved form of posttranslational modifications of proteins,which plays an important role in a series of cellular physiological and pathological *** e-amino groups are the primary sites of such modification,resulting in four-carbon planar lysine crotonylation that is structurally and functionally distinct from the acetylation of these *** levels of Kcr modifications have been identified on both histone and non-histone *** present review offers an update on the research progression regarding protein Kcr modifications in biomedical contexts and provides a discussion of the mechanisms whereby Kcr modification governs a range of biological *** addition,given the importance of protein Kcr modification in disease onset and progression,the potential viability of Kcr regulators as therapeutic targets is elucidated.

关键词： Cell biology Disease Lysine crotonylation Posttranslational modification Therapeutic target

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New perspectives on the therapeutic potential of quercetin in non-communicable diseases:Targeting Nrf2 to counteract oxidative stress and inflammation

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Journal of Pharmaceutical Analysis 2024年第6期14卷 805-822页

作者： Li Zhang Li-Yue Xu Fei Tang Dong Liu Xiao-Lan Zhao Jing-Nan Zhang Jia Xia Jiao-Jiao Wu Yu Yang Cheng Peng Hui Ao State Key Laboratory of Southwestern Chinese medicine Resources School of PharmacyChengdu University of Traditional Chinese MedicineChengdu611137China Innovative institute of Chinese medicine and Pharmacy Chengdu University of Traditional Chinese MedicineChengdu611137China

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health *** complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory *** factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated ***,Nrf2-targeting therapies hold promise for preventing and treating ***(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory *** modulates the Nrf2 signaling pathway to ameliorate oxidative stress and *** modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against ***,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone ***,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applications of Que in treating *** addition,we focused on the challenges and prospects for its clinical *** represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

关键词： Quercetin Nrf2 Non-communicable diseases Antioxidant Anti-inflammatory Availability

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Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units

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Neural Regeneration Research 2024年第4期19卷 887-894页

作者： Yifang Wu Jun Sun Qi Lin Dapeng Wang Jian Hai Department of Neurosurgery Tongji HospitalSchool of MedicineTongji University Department of Pharmacy Institute of Medical SciencesShanghai Jiao Tong University School of Medicine

Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective ***,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently *** this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning *** found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 *** 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose ***,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved ***,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

关键词： brain ischemia brain microvascular endothelial cell nanofiber membrane neurovascular unit

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Molecular characterization and structure basis of a malonyltransferase with both substrate promiscuity and catalytic regiospecificity from Cistanche tubulosa

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2333-2348页

作者： Xiao Liu Yuyu Liu Xiping Xu Wenqian Huang Yaru Yan Yingxia Wang Weisheng Tian Ting Mo Xiaoxue Cui Jun Li She-Po Shi Pengfei Tu Modern Research Center for Traditional Chinese medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Modern Research Center for Traditional Chinese medicine School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China

Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides ***,the catalytic potential and structural basis of plant malonyltransferase are far from being fully *** work identified a new malonyltransferase CtMaT1 from Cistanche *** displayed unprecedented mono-and/or di-malonylation activity toward diverse glucosides with different aglycons.A“one-pot”system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated *** investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse ***,it recognizes malonyl-CoA through strong electrotactic and hydrogen ***/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1,while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167,resulting in its high malonylation *** energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates,emphasizing CtMaT1's preference for ***,a mutant CtMaT1H36A with notably increased di-malonylation activity was *** underlying molecular mechanism was illuminated through MM/GBSA binding free energy *** study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives,while also providing a versatile tool for enzymatic malonylation applications in pharmacology.

关键词： Plant acyltransferase Malonyltransferase Malonylated glycosides Enzymatic catalysis Enzyme promiscuity

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A novel metal-free porous covalent organic polymer for efficient room-temperature photocatalytic CO2 reduction via dry-reforming of methane

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Green Energy & Environment 2024年第09期9卷 1407-1418页

作者： Sheng-Yan Yin Ziyi Li Yingcai Hu Xiao Luo Jishan Li College of Chemistry and Chemical Engineering Hunan University institute of Basic medicine and Cancer (IBMC) Chinese Academy of Sciences

At room temperature,the conversion of greenhouse gases into valuable chemicals using metal-free catalysts for dry reforming of methane（DRM） is quite promising and ***,we developed a novel covalent organic porous polymer （TPE-COP） with rapid charge separation of the electron–hole pairs for DRM driven by visible light at room temperature,which can efficiently generate syngas （CO and H2）.Both electron donor (tris（4-aminophenyl）amine,TAPA) and acceptor (4,4',4'',4'''-(（1 E,1'E,1''E,1'''E）-(ethene-1,1,2,2-tetrayltetrakis （benzene-4,1-diyl）)tetrakis （ethene-2,1-diyl）)tetrakis (1-（4-formylbenzyl）quinolin-1-ium),TPE-CHO) were existed in TPE-COP,in which the push–pull effect between them promoted the separation of photogenerated electron–hole,thus greatly improving the photocatalytic *** functional theory （DFT） simulation results show that TPE-COP can form charge-separating species under light irradiation,leading to electrons accumulation in TPE-CHO unit and holes in TAPA,and thus efficiently initiating *** 20 h illumination,the photocatalytic results show that the yields reach 1123.6 and 30.8μmol g-1for CO and H2,respectively,which are significantly higher than those of TPE-CHO small *** excellent result is mainly due to the increase of specific surface area,the enhancement of light absorption capacity,and the improvement of photoelectron-generating efficiency after the formation of ***,this work contributes to understanding the advantages of COP materials for photocatalysis and fundamentally pushes metal-free catalysts into the door of DRM field.

关键词： Metal-free Photocatalytic CO 2 reduction Covalent organic polymer Dry-reforming of methane Electron donor and acceptor

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Promising use of metformin in treating neurological disorders:biomarker-guided therapies

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Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui Ling He Jing Wang Regenerative medicine Program Ottawa Hospital Research InstituteOttawaONCanada Department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada Department of Pediatrics and medicine Johns Hopkins Medical SchoolBaltimoreMDUSA Department of Cellular and Molecular medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available *** most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy ***,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological *** that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological *** molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted *** this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

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Absorbed Bioactive Compounds Replicate GuanxinⅡ-Induced Endothelium-Associated in/ex vivo Vasodilation

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Chinese Journal of Integrative medicine 2024年第5期30卷 387-397页

作者： XU Min LIU Hao SU Meng-qing LI Lan YU Ai-ling CHEN Ken HUANG Yun-ke ZHAO Qiu-long HUANG Wen-ya HUANG Xi institute of Traditional Chinese medicine Related Comorbid Depression Nanjing University of Chinese MedicineNanjing 210029China Department of Gynecology Women's HospitalZhejiang University School of MedicineHangzhou 310053China

Objective:To develop an interference-free and rapid method to elucidate GuanxinⅡ(GXⅡ)'s representative vasodilator absorbed bioactive compounds(ABCs)among enormous ***:The contents of ferulic acid,tanshinol,and hydroxysafflor yellow A(FTA)in GXⅡ/rat serum after the oral administration of GXⅡ(30 g/kg)were detected using ultra-performance liquid chromatography-mass *** 18 rats were randomly assigned to the control group(0.9%normal saline),GXⅡ(30 g/kg)and FTA(5,28 and 77 mg/kg)by random number table *** coronary flow velocity-time integral(VTI),i.e.,coronary flow or coronary flow-mediated dilation(CFMD),and endothelium-intact vascular tension of isolated aortic rings were *** 12 h of exposure to blank medium or 0.5 mmol/L H_(2)O_(2),endothelial cells(ECs)were treated with post-dose GXⅡof supernatant from deproteinized serum(PGSDS,300μL PGSDS per 1 m L of culture medium)or FTA(237,1539,and 1510 mg/m L)for 10 min as control,H_(2)O_(2),PGSDS and FTA *** oxide(NO),vascular endothelial growth factor(VEGF),endothelin-1(ET-1),superoxide dismutase(SOD),malondialdehyde(MDA)and phosphorylated phosphoinositide 3 kinase(p-PI3K),phosphorylated protein kinase B(p-AKT),phosphorylated endothelial nitric oxide synthase(p-e NOS)were *** was developed as a GXⅡproxy of ex vivo herbal crude ***:PGSDS effectively eliminates false responses caused by crude GXⅡ*** doses equaled the contents in GXⅡ/its post-dose serum,FTA accounted for 98.17%of GXⅡ-added CFMD and 92.99%of PGSDS-reduced vascular *** ECs,FTA/PGSDS was found to have significant antioxidant(lower MDA and higher SOD,P<0.01)and endothelial function-protective(lower VEGF,ET-1,P<0.01)*** increases in aortic relaxation,endothelial NO levels and phosphorylated PI3K/Akt/e NOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester(L-NA,e NOS inhibitor)and wortmannin(PI3K/AKT inhibitor

关键词： ultra-performance liquid chromatography-mass spectrometry endothelium-dependent vasodilation herbal extract GuanxinⅡ absorbed bioactive compound

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The crosstalk between enteric nervous system and immune system in intestinal development,homeostasis and diseases

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Science China(Life Sciences) 2024年第1期67卷 41-50页

作者： Xindi Wang Chenbo Ding Hua-Bing Li Shanghai institute of Immunology State Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Jiao Tong University School of medicine-Yale institute for Immune Metabolism Shanghai Jiao Tong University School of MedicineShanghai 200025China

The gut is the largest digestive and absorptive organ,which is essential for induction of mucosal and systemic immune responses,and maintenance of metabolic-immune *** intestinal components contain the epithelium,stromal cells,immune cells,and enteric nervous system(ENS),as well as the outers,such as gut microbiota,metabolites,and *** dyshomeostasis of intestinal microenvironment induces abnormal intestinal development and functions,even colon diseases including dysplasia,inflammation and *** recent studies have identified that ENS plays a crucial role in maintaining the immune homeostasis of gastrointestinal(GI)*** crosstalk between ENS and immune cells,mainly macrophages,T cells,and innate lymphoid cells(ILCs),has been found to exert important regulatory roles in intestinal tissue programming,homeostasis,function,and *** this review,we mainly summarize the critical roles of the interactions between ENS and immune cells in intestinal homeostasis during intestinal development and diseases progression,to provide theoretical bases and ideas for the exploration of immunotherapy for gastrointestinal diseases with the ENS as potential novel targets.

关键词： enteric nervous system macrophages T cells innate lymphoid cells neuro-immune interactions

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Reconstruction of Postinfarcted Cardiac Functions Through Injection of Tanshinone IIA@ Reactive Oxygen Species-Sensitive Microspheres Encapsulated in a Thermoreversible Hydrogel

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Energy & Environmental Materials 2024年第2期7卷 191-203页

作者： Ling Yu Yubin Liang Lei Gao Peipei Chen Zhiqiang Yu Minzhou Zhang Aleksander Hinek Shuai Mao Second Clinical College Guangzhou University of Chinese Medicine Department of Critical Care medicine Guangdong Provincial Hospital of Chinese Medicine Guangdong Provincial Branch of National Clinical Research Centre for Chinese medicine Cardiology Department of Radiation medicine and Applied Sciences University of California San Diego Department of Laboratory medicine Dongguan Institute of Clinical Cancer Research Affiliated Dongguan Hospital Southern Medical University Translational medicine Hospital for Sick Children

Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death, highlighting the urgent clinical need for effective therapies. Recently, tanshinone IIA has been identified as a promising therapeutic agent for myocardial infarction. However, efficient delivery remains a major issue that limits clinical translation. To address this problem, an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid) gel(PLGA-PEG-PLGA) system encapsulating tanshinone IIA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinone IIA) has been designed and synthesized in this study. The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature. Microspheres initially immobilized by the gel exhibit excellent reactive oxygen speciestriggered release properties in a high-reactive oxygen species environment after myocardial infarction onset. As a result, encapsulated tanshinone IIA is effectively released into the infarcted myocardium, where it exerts local antipyroptotic and anti-inflammatory effects. Importantly, the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinone ***, this novel, precision-guided intra-tissue therapeutic system allows for customized local release of tanshinone IIA, presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.

关键词： myocardial infarction ROS-sensitive polymer tanshinone IIA thermoreversible hydrogel ventricular remodeling

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