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Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution

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Journal of Traditional Chinese medicine 2024年第1期44卷 188-196页

作者： ZHU Linghui SUN Ziwei GUAN Yuanyuan LIU Meiyi ZHENG Yi YU Ruoxi WANG Qi LI Lingru School of Chinese medicine Beijing University of Chinese MedicineBeijing 102488China National institute of TCM Constitution and Preventive medicine Beijing University of Chinese MedicineBeijing 100029China

OBJECTIVE:To evaluate the extent of vascular endothelial dysfunction and preliminary identify serum protein biomarkers associated with obese individuals at risk for cardiovascular disease(CVD).METHODS:Fifteen obese volunteers with the phlegmdampness constitution or balanced constitution were recruited for this study *** clinical baseline data was collected,and the vascular endothelial function was evaluated using the EndoPAT?.Blood samples were collected for the serum proteome *** differences in the serum protein expression levels between the two groups were detected and the protein interaction network analysis,correlation analysis,receiver operating characteristic(ROC)curve analysis,and random forest model investigation were ***:There were no statistical differences found in the baseline *** vascular endothelial function,the reactive hyperemia index(RHI)of the phlegm-dampness constitution obese group was significantly lower than that of the balanced constitution obese group(1.46±0.30 vs 2.82±0.78,P<0.0001),indicating vascular endothelial *** are 66 differentially expressed serum proteins between the two *** A2(Apo A2),angiotensin-converting enzyme 2(ACE-2),interleukin-33(IL-33),and forkhead box P3(FoxP3)showed significant differences and area under curve values of their ROC curves were greater than 0.7 and correlated significantly with ***:Vascular endothelial dysfunction was present in the phlegm-dampness constitution obese ***,alterations in the expression levels of key serum proteins,including Apo A2,ACE-2,IL-33,and Fox P3 could serve as potential biomarkers in the obese population at risk of CVD.

关键词： obesity phlegm-dampness constitution vascular endothelial function proteome reactive hyperemia index

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

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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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Inverse relationship between platelet Akt activity and hippocampal atrophy:A pilot case-control study in patients with diabetes mellitus

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World Journal of Clinical Cases 2024年第2期12卷 302-313页

作者： Haruhiko Tokuda Takamitsu Hori Daisuke Mizutani Tomoyuki Hioki Kumi Kojima Takashi Onuma Yukiko Enomoto Tomoaki Doi Rie Matsushima-Nishiwaki Shinji Ogura Hiroki Iida Toru Iwama Takashi Sakurai Osamu Kozawa Department of Metabolic Research Research InstituteNational Center for Geriatrics and GerontologyObu 474-8511Japan Department of Clinical Laboratory National Center for Geriatrics and GerontologyObu 474-8511Japan Department of Pharmacology Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Neurosurgery Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Dermatology Central Japan International Medical CenterMinokamo 505-8510Japan Department of Anesthesiology and Pain medicine Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Emergency medicine Faculty of MedicineUniversity of ToyamaToyama 930-0194Japan Department of Emergency and Disaster medicine Gifu University Graduate School of MedicineGifu 501-1194Japan Research institute National Center for Geriatrics and GerontologyObu 474-8511Japan

BACKGROUND Akt plays diverse roles in *** is involved in the pathogenesis of type 2 diabetes mellitus(T2DM),which is caused by insulin *** also plays a vital role in human platelet ***,the hippocampus is closely associated with memory and learning,and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without *** To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM *** Platelet-rich plasma(PRP)was prepared from the venous blood of patients with T2DM or age-matched *** pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt,p38 mitogen-activated protein(MAP)kinase and glyceraldehyde 3-phosphate dehydrogenase(GAPDH).Phosphorylation levels were quantified by densitometric *** volume was analysed using a voxel-based specific regional analysis system for Alzheimer’s disease on magnetic resonance imaging,which proposes the Z-score as a parameter that reflects hippocampal *** The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects,whereas the levels of phosphorylated Akt corrected with GAPDH were ***,this relationship was not observed in the control *** These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM *** findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.

关键词： Akt Platelet Hippocampal atrophy Magnetic resonance imaging Diabetes mellitus

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Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

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Journal of Pharmaceutical Analysis 2024年第4期14卷 601-614页

作者： Bei Li Yong Zhang Xinyuan Liu Ziyang Zhang Shuqing Zhuang Xiaoli Zhong Wenbo Chen Yilin Hong Pingli Mo Shuhai Lin Shicong Wang Chundong Yu State Key Laboratory of Cellular Stress Biology School of Life SciencesXiamen UniversityXiamen361102China Fujian Pien Tze Huang Enterprise Key Laboratory of natural medicine Research and Development ZhangzhouFujian363000China Xiang'an Hospital of Xiamen university School of MedicineXiamen UniversityXiamen361005China Department of Cardiology Xiamen Key Laboratory of Cardiac ElectrophysiologyXiamen Institute of Cardiovascular DiseasesThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361003China

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is ***,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)***,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK *** of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating ***,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory ***,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

关键词： Pien Tze Huang Bile acids Sepsis Inflammation TGR5 STAT3-A20 signalling

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One-pot and One-step Cu(0)-mediated Reversible-Deactivation Radical Polymerization of N-Isopropylacrylamide(NIPAM) in Water

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Chinese Journal of Polymer Science 2024年第1期42卷 1-6,I0004页

作者： Zi-Shan Li Jing Lyu Bei Qiu Ying-Hao Li Ruth Foley Ri-Jian Song Melissa Johnson Qiang Geng Wen-Xin Wang institute of Precision medicine(AUST-IPM) Anhui University of Science and TechnologyHuainan 232001China Charles institute of Dermatology School of MedicineUniversity College DublinDublin D04 V1W8Ireland

Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control over the molecular weights(MWs) or complex or multi reaction steps, etc. In this work, we report the well-controlled polymerization of NIPAM in water via a facile one-pot and one-step Cu(0)-mediated RDRP. The results of this approach show that the key for kicking off the Cu(0)-mediated NIPAM RDRPs is to ensure sufficient Cu~I at the very beginning, and the key to achieve a well-controlled chain growth is to provide adequate deactivation strength during the polymerization process. For NIPAM, which has a high propagation rate constant, the deactivation control can be effectively enhanced by extra adding deactivator(i.e., Cu~II) to the system. Moreover, a low reaction temperature(4 ℃) is necessary in the controlled synthesis of higher MW poly(Nisopropylacrylamide)(PNIPAM) to avoid the compromise in control caused by the phase transition from its lower critical solution temperature(LCST). Through this new kinetically controlled strategy, PNIPAMs with well-defined structure, narrow molecular weight distributions(MWDs) and varied MWs were successfully achieved.

关键词： Cu(0)-mediated RDRP N-isopropylacrylamide Propagation Deactivation Reaction parameters

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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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Luteolin promotes neuronogenesis in hippocampus of chronic unpredictable mild stress rats and primary hippocampus of fetal rats

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Journal of Traditional Chinese medicine 2024年第4期44卷 670-679页

作者： LIU Tongtong ZHANG Xi YANG Hui LIN Xiaoyuan LIU Jian ZHANG Xiuli GUO Dongwei ZHAO Hongqing ZOU Manshu LEI Chang LONG Hongping LUO Yan XIANG Yun GE Jinwen WANG Yuhong MENG Pan institute of Innovation and Applied Research in Chinese medicine Hunan University of Chinese Medicine the Second People's Hospital of Hunan Province The First Affiliated Hospital Hunan University of Chinese Medicine Hunan Academy of Chinese medicine

OBJECTIVE: To investigate the effects of luteolin on chronic unpredictable mild stress(CUMS)-induced depressive rats and corticosterone(CORT)-induced depressive primary hippocampal neurons, and to elucidate the mechanism behind the ***: The antidepressant mechanism of luteolin was studied by using CUMS rat model and primary hippocampal neurons in fetal rats. In vivo, novelty suppressed feeding, open-field and sucrose preference tests as well as Morris water maze were evaluated. The content of brain derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), norepinephrine(NE), and dopamine(DA) in serum were detected by enzyme-linked immunosorbent assay. The mechanisms of luteolin were explored based on neurotrophin and hippocampal neurogenesis, and proliferation. Survival of the septotemporal axis in hippocampus was assayed using the 5-bromo-2-deoxyuridine(BrdU), the expression of BDNF,neurotrophin-3(NT-3), and nerve growth factor(NGF) in hippocampus dentate gyrus region were measured by Western-blotting. In vitro, BDNF, NT-3, tropomyosin receptor kinase B(TrkB), and phosphorylated cyclic adenosine monophosphate responsive element binding protein(p-CREB) were detected through the high content analysis(HCA) to investigate neurotrophin and ***: Induction of CUMS in rats induced depressive symptoms, while luteolin significantly enhanced sucrose consumption, decreased feeding latency, increased locomotor activity, escape latency, distance of target quadrant and regulated the content of depressive-like biomarkers. Histology analysis revealed that luteolin increased the abundance of new born neurons that had been labeled with BrdU, BrdU + neuronal nuclear antigen,and BrdU + doublecortin in septo-temporal axis of S2(mid-septal) and T3(mid-temporal). Moreover,expression of BDNF, NT-3, and NGF increased significantly in the septo-temporal axis of S2 and T3. HCA showed increased expression of BDNF, NT-3, TrkB and p-CREB in primary hippocampal neuron

关键词： chronic unpredicted mild stress depression hippocampal neurogenesis luteolin septo-temporal axis

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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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The regulatory role of m^(6)A modification in the maintenance and differentiation of embryonic stem cells

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Genes & Diseases 2024年第5期11卷 126-139页

作者： Jin Zhang Lingling Tong Yuchen Liu Xiang Li Jiayi Wang Ruoxin Lin Ziyu Zhou Yunbing Chen Yanxi Chen Yirong Liu Di Chen Center for Reproductive medicine of the Second Affiliated Hospital Center for Regeneration and Cell Therapy of Zhejiang University-University of Edinburgh Institute(ZJU-UoE Institute)Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang 310003China Zhejiang university-university of Edinburgh institute(ZJU-UoE institute) Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang 310003China College of Materials and Chemical Engineering Minjiang UniversityFuzhouFujian 350108China National Key Laboratory of Biobased Transportation Fuel Technology HainingZhejiang 314400China

As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs,N6-methyladenosine(m^(6)A)post-transcriptionally regulates the processing and metabolism of mRNAs involved in diverse biological processes.m^(6)A modification is regulated by m^(6)A writers,erasers,and *** evidence suggests that m^(6)A modification plays essential roles in modulating the cell-fate transition of embryonic stem *** investigation of embryonic stem cell maintenance and differentiation is critical for understanding early embryonic development,which is also the premise for the application of embryonic stem cells in regenerative *** review highlights the current knowledge of m^(6)A modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.

关键词： Cell-fate transition Embryonic stem cell Epigenetic modification m^(6)A modification Post-transcriptional regulation

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Small moleculeα-methylene-γ-butyrolactone,an evolutionarily conserved moiety in sesquiterpene lactones,ameliorates arthritic phenotype via interference DNA binding activity of NF-κB

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3561-3575页

作者： Kegang Linghu Wenqing Cui Taiqin Li Yueting Tuo Dasong Wang Huiqi Pan Tian Zhang Ligen Lin Hua Yu Xiaoxia Hu Haiyang Li Xiangchun Shen Department of Surgery the Affiliated Hospital of Guizhou Medical UniversityGuiyang 550001China The Key Laboratory of Optimal Utilization of natural medicine Resources School of Pharmaceutical SciencesGuizhou Medical UniversityGuian New DistrictGuizhou 561113China State Key Laboratory of Quality Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China Guizhou institute of Precision medicine Affiliated Hospital of Guizhou Medical UniversityGuiyang 550001China

Rheumatoid arthritis(RA)is an inflammatory disease accompanied by abnormal synovial microenvironment(SM).Sesquiterpene lactones(SLs)are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment.α-Methylene-γ-butyrolactone(α-M-γ-B)is a core moiety that widely exists in natural *** study was designed to investigate the anti-arthritic potential ofα-M-γ-B as an independent small molecule in vitro and in vivo.α-M-γ-B exhibited stronger electrophilicity and anti-inflammatory effects than the other six analogs.α-M-γ-B inhibited the production of pro-inflammatory mediators via repolarizing M1 macrophages into M2 *** transcriptome sequencing suggested thatα-M-γ-B regulated the immune system ***,α-M-γ-B attenuated collagen type II-induced arthritic(CIA)phenotype,restored the balance of Tregs-macrophages and remodeled SM via repolarizing the synovial-associated macrophages in CIA ***,althoughα-M-γ-B did not prevent the trans-nucleus of NF-κB it interfered with the DNA binding activity of NF-κB via direct interaction with the sulfhydryl in cysteine residue of NF-κB p65,which blocked the activation of NF-κ*** of NF-κB reduced the M1 polarization of macrophage and suppressed the synovial hyperplasia and angiogenesis.α-M-γ-B failed to ameliorate CIA in the presence of N-acetylcysteine or when the mice were subjected to the macrophage-specific deficiency of *** conclusion,α-M-γ-B significantly attenuated the CIA phenotype by directly targeting NF-κB p65 and inhibiting its DNA binding *** results suggest thatα-M-γ-B has the potential to serve as an alternative candidate for treating *** greater electrophilicity ofα-M-γ-B,the basis for triggering strong anti-inflammatory activity,accounts for the reason whyα-M-γ-B is evolutionarily conserved in the SLs by medical plants.

关键词： a-Methylene-gbutyrolactone Rheumatoid arthritis NF-κB p65 Synovial microenvironment Sesquiterpene lactones

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