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Electroacupuncture ameliorates blood-brain barrier disruption after ischemic stroke through histone acetylation regulation at the matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 2 genes

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Journal of Traditional Chinese medicine 2024年第4期44卷 734-744页

作者： CHEN Yonglin OUYANG Ling MENG Lingling WU Bufan PENG Rou LIU Sitong HOU Dan WANG Yaling JING Xinyue LU Shengfeng FU Shuping key laboratory of Acupuncture and medicine Research of ministry of education Nanjing University of Chinese Medicine

OBJECTIVE: To explore whether the regulation of matrix metalloproteinase 9(MMP-9)/tissue inhibitors of MMPs(TIMPs) gene expression through histone acetylation is a possible mechanism by which electroacupuncture(EA)protects blood-brain barrier(BBB) integrity in a middle cerebral artery occlusion(MCAO) rat ***: Male Sprague-Dawley rats were divided into four groups: the sham group, the MCAO group, the MCAO + EA(MEA) group, and the MCAO + EA + HAT inhibitor(HATi) group. The MCAO model was generated by blocking the middle cerebral artery. EA was applied to Baihui(GV20). Samples were collected 1 or 3 d after reperfusion. Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury. The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and chromatin immunoprecipitation(ChIP). RESULTS: Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption. The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression, but HATi reversed these effects of EA. In addition, ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter. CONCLUSION: EA treatment at Baihui(GV20) regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke, which preserves the structural integrity of the BBB in MCAO rats. These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.

关键词： blood-brain barrier electroacupuncture histone acetylation matrix metalloproteinase 9 tissue inhibitor of metalloproteinases

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Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

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Zoological Research 2024年第2期45卷 253-262页

作者： Yang Han Jiale Zhou Renquan Zhang Yuru Liang Liangxue Lai Zhanjun Li key laboratory of Zoonosis Research Ministry of EducationCollege of Animal ScienceJilin UniversityChangchunJilin 130062China CAS key laboratory of regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Guangzhou regenerative medicine and Health Guang Dong laboratory(GRMH-GDL) GuangzhouGuangdong 510005China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene *** field of genome modification in rabbits has progressed ***,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic *** models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to *** review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

关键词： Genome editing Animal model Rabbit CRISPR/Cas9 Genetic diseases

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LncRNA CCRR maintains Ca^(2+)homeostasis against myocardial infarction through the FTO-SERCA2a pathway

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Science China(Life Sciences) 2024年第8期67卷 1601-1619页

作者： Hua Yang Lina Xuan Shengjie Wang Huishan Luo Xiaomeng Duan Jianjun Guo Shijia Cui Jieru Xin Junwei Hao Xiufang Li Jun Chen Feihan Sun Xiaolin Hu Siyun Li Ying Zhang Lei Jiao Baofeng Yang Lihua Sun Department of Pharmacology Harbin Medical University(State Key Laboratory of Frigid Zone Cardiovascular Diseasethe State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of EducationJoint International Research Laboratory of Cardiovascular Medicine ResearchMinistry of EducationChina)College of PharmacyHarbin Medical UniversityHarbin 150081China

Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier *** study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following *** effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full ***,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of *** increased SERCA2a protein stability by upregulating FTO *** direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown *** of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in *** study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in ***,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

关键词： CCRR calcium homeostasis FTO myocardial infarction SERCA2a

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Mapping out the reaction network of humin formation at the initial stage of fructose dehydration in water

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Green Energy & Environment 2024年第6期9卷 1016-1026页

作者： Xing Fu Yexin Hu Ping Hu Hui Li Shuguang Xu Liangfang Zhu Changwei Hu key laboratory of Green Chemistry and Technology Ministry of EducationCollege of ChemistrySichuan UniversityChengduSichuan610064China State key laboratory of Southwestern Chinese medicine Resources Innovative Institute of Chinese Medicine and PharmacyChengdu University of Traditional Chinese MedicineChengduSichuan611137China

The formation of humins hampers the large-scale production of 5-hydroxymethylfurfural(HMF)in ***,a detailed reaction network of humin formation at the initial stage of fructose-to-HMF dehydration in water is delineated by combined experimental,spectroscopic,and theoretical *** bimolecular reaction pathways to build up soluble humins are *** is,the intermolecular etherification of β-furanose at room temperature initiates the C12 path,whereas the C-C cleavage of a-furanose at 130-150℃ leads to C11 path,and that of open-chain fructose at 180℃ to C11' *** successive intramolecular dehydrations and condensations of the as-formed bimolecular intermediates lead to three types of soluble *** show that the C12 path could be restrained by using HCl or AlCl_(3) catalyst,and both the C12 and C110 paths could be effectively inhibited by adding THF as a co-solvent or accelerating heating rate via microwave heating.

关键词： Carbohydrates 5-hydroxymethylfurfural Reaction network Soluble humins Tautomer

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Gut-targeted therapies for type 2 diabetes mellitus: A review

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World Journal of Clinical Cases 2024年第1期12卷 1-8页

作者： Tian-Cheng Xu Yun Liu Zhi Yu Bin Xu key laboratory of Acupuncture and medicine Research of ministry of education Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder characterized by hyperglycemia and insulin *** global prevalence of T2DM has reached epidemic proportions,affecting approximately 463 million adults worldwide in *** treatments for T2DM include lifestyle modifications,oral antidiabetic agents,and insulin ***,these therapies may carry side effects and fail to achieve optimal glycemic control in some ***,there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of *** gut microbiota,which refers to the community of microorganisms that inhabit the human gut,has been shown to play a crucial role in the regulation of glucose metabolism and insulin *** in gut microbiota composition and diversity have been observed in T2DM patients,with a reduction in beneficial bacteria and an increase in pathogenic *** dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier *** gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in *** potential approach is the use of probio-tics,which are live microorganisms that confer health benefits to the host when administered in adequate *** randomized controlled trials have demonstrated that certain probiotics,such as Lactobacillus and Bifidobacterium species,can improve glycemic control and insulin sensitivity in T2DM *** may include the production of short-chain fatty acids,the improvement of gut barrier function,and the reduction of *** gut-targeted therapy is fecal microbiota transplantation(FMT),which involves the transfer of fecal material from a healthy donor to a *** has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM.A recent rand

关键词： Type 2 diabetes mellitus Gastroenterology Bacteria Implanted device

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Layer by Layer Self-assembly Fiber-based Flexible Electrochemical Transistor

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Journal of Wuhan University of Technology(Materials Science) 2024年第4期39卷 937-944页

作者：谭艳 HAO Panpan HE Yang ZHU Rufeng 王跃丹 School of Biomedical Engineering Hubei University of MedicineShiyan 442000China key laboratory of Textile Fiber and Products Ministry of EducationWuhan Textile UniversityWuhan 430200China

Poly(3,4-ethylenedioxyethiophene)-polystyrene sulfonic acid(PEDOT:PSS)/polyallyl dimethyl ammonium chloride modified reduced graphene oxide(PDDA-rGO)was layer by layer self-assembled on the cotton *** surface morphology and electric property was *** results confirmed the dense membrane of PEDOT:PSS and the lamellar structure of PDDA-rGO on the *** has excellent electrical conductivity and mechanical *** fiber based electrochemical transistor(FECTs)prepared by the composite conductive fiber has a maximum output current of 8.7 mA,a transconductance peak of 10 mS,an on time of 1.37 s,an off time of 1.6 s and excellent switching *** importantly,the devices by layer by layer self-assembly technology opens a path for the true integration of organic electronics with traditional textile technologies and materials,laying the foundation for their later widespread application.

关键词： layer by layer self-assembly fiber based organic electrochemical transistor reduced graphene oxide PEDOT:PSS

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CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

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Science China Life Sciences 2024年第9期67卷 1881-1898页

作者： Jiaxin Chen Huijuan Wang Jianbin Xu Engeng Chen Qing Meng Jiawei Wang Haoyi Xiang Wei Zhou Ge Shan Zhenyu Ju Zhangfa Song Department of Colorectal Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine key laboratory of Biological Treatment of Zhejiang Province Department of Breast Surgery the Second Affiliated Hospital Zhejiang University School of Medicine Department of Orthopedic Surgery the Second Affiliated Hospital Zhejiang University School of Medicine Department of Pulmonary and Critical Care medicine Regional medical center for National Institute of Respiratory Disease Sir Run Run Shaw Hospital Zhejiang University School of Medicine key laboratory of regenerative medicine of ministry of education Institute of Aging and Regenerative Medicine Jinan University

Aberrant expression of circular RNAs(circ RNAs) is frequently linked to colorectal cancer(CRC). Here, we identified circ ZFR as a promising biomarker for CRC diagnosis and prognosis. Circ ZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence, advanced-stages, and metastasis. In both in vitro and in vivo settings, circ ZFR promoted the growth and spread while suppressing apoptosis of CRC. Exosomes with circ ZFR overexpression promoted the proliferation and migration of cocultured CRC cells. Mechanistically,epithelial splicing regulatory protein 1(ESRP1) in CRC cells may enhance the production of circ ZFR. BCL2-associated transcription factor 1(BCLAF1) bound to circ ZFR, which prevented its ubiquitinated degradation. Additionally, circ ZFR sponged mi R-3127-5p to boost rhotekin 2(RTKN2) expression. Our TCP1-CD-QDs nanocarrier was able to carry and deliver circ ZFR si RNA(si-circ ZFR) to the vasculature of CRC tissues and cells, which inhibited the growth of tumors in patient-derived xenograft(PDX) models. Taken together, our results show that circ ZFR is an oncogenic circ RNA, which promotes the development and spread of CRC in a BCLAF1 and mi R-3127-5p-dependent *** ZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.

关键词： circZFR exosome ESRP1 BCLAF1 miR-3127-5p nanoparticle (NP)

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A booming field of large animal model research

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Zoological Research 2024年第2期45卷 311-313页

作者： Xiao-Jiang Li Liangxue Lai Guangdong key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)GHM Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China State key laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhouGuangdong 510632China CAS key laboratory of regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China

Animal models are integral to the study of fundamental biological processes and the etiology of human *** animal models,especially those involving mice,have yielded abundant and significant insights,greatly enhancing ... 详细信息

关键词： mechanisms insight field

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Pathological BBB Crossing Melanin-Like Nanoparticles as Metal-Ion Chelators and Neuroinflammation Regulators against Alzheimer’s Disease

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Research 2024年第1期6卷 687-706页

作者： Qianqian Huang Chaoqing Jiang Xue Xia Yufan Wang Chenxing Yan Xiaorong Wang Ting Lei Xiaotong Yang Wenqin Yang Guo Cheng Huile Gao key laboratory of Drug-Targeting and Drug Delivery System of the education ministry West China School of PharmacySichuan UniversityChengdu 610041P.R.China laboratory of Molecular Translational medicine Center for Translational MedicineKey Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationDepartment of PediatricsWest China Second University HospitalSichuan UniversityChengdu 610041P.R.China

Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD ***,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of *** this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβ*** vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB *** engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.

关键词： oxidative aggregation chelating

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Cucurbit[8]uril-regulated face-to-face dimerization assembly enhanced photosensitization and photocatalysis

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Science China Chemistry 2024年第5期67卷 1605-1612页

作者： Haigen Nie Die Hu Zhiyao Zeng Yan Fan Yaxin Zhai Xin-Long Ni key laboratory of Chemical Biology and Traditional Chinese medicine Ministry of Educational of ChinaKey Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan ProvinceCollege of Chemistry and Chemical EngineeringHunan Normal UniversityChangsha 410081China key laboratory of Low-Dimensional Quantum Structures and Quantum Control of ministry of education Department of PhysicsHunan Normal UniversityChangsha 410081China

In water, N,N′-diarylpyridinium thiazolo[5,4-d]thiazole guests(G1–G3) were encapsulated by cucurbit[8]uril(Q[8]) to construct Q[8]_(3)/G_(2) complexes, in which the encapsulated G molecules exist as an exact face-to-face dimer. These complexation behaviors have been indicated by proton nuclear magnetic resonance(~1H NMR) spectroscopy and isothermal titration calorimetry(ITC),and have been confirmed by X-ray single crystal structural analysis of Q[8]_(3)/G2_(2). While free guests G1–G3 have no ability to sensitize singlet oxygen, they all become effective singlet oxygen sensitizers when complexed with Q[8]. By irradiation of white light, Q[8]_(3)/G_(2) complexes induced selective oxidation of aryl sulfide to aryl sulfoxide in good yields and selective oxidation of dimethyl sulfide(DMS) to dimethyl sulfoxide(DMSO) in excellent yields without over-oxidation to dimethyl sulfone(DMSO_(2))even for elongated irradiation. High-yield photo-oxidation of DMS to DMSO_(2) was only achieved by irradiation of blue light in the presence of Q[8]_(3)/G1_(2), which was also effective in photobleaching of Rhodamine B in water. The higher photo-oxidation power of Q[8]_(3)/G1_(2) has been ascribed to an additional generation of reactive oxygen species besides singlet oxygen.

关键词： host-guest interaction dimerization macrocycles photosensitization

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