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Acupotomy alleviates knee osteoarthritis in rabbit by regulating chondrocyte mitophagy via Pink1-Parkin pathway

Journal of Traditional Chinese Medicine 2024年第3期44卷 468-477页

作者： ZHU Wenting GUO Changqing DU Mei MA Yunxuan CUI Yongqi CHEN Xilin GUO Changqing the Third Affiliated Hospital of Beijing university of Chinese Medicine school of Acupuncture-Moxibustion and Tuina Beijing University of Chinese Medicine Department of medical Technology Shijiazhuang Medical College

OBJECTIVE: To investigate the effect of acupotomy, on mitophagy and the Pink1-Parkin pathway in chondrocytes from rabbits with knee osteoarthritis(KOA).METHODS: A KOA model was established via the modified Videman method. Rabbits were randomly divided into a control group(CON), KOA group and KOA + acupotomy group(Acu). Rabbits in the acupotomy group were subjected to acupotomy for 4 weeks after model establishment. The behavior of the rabbits before and after intervention was recorded. Cartilage degeneration was evaluated by optical microscopy and fluorescence microscopy. The level of mitophagy was evaluated by transmission electron microscopy,immunofluorescence and enzyme-linked immunosorbent assay(ELISA). The expression of phosphatase and tensin homolog(PTEN)-induced kinase 1(Pink1)-Parkin mitophagy pathway components was evaluated by immunofluorescence, Western blotting and real-time polymerase chain ***: In rabbits with KOA, joint pain, mobility disorders and cartilage degeneration were observed, the Mankin score was increased, collagen type Ⅱ(Col-Ⅱ)expression was significantly decreased, mitophagy was inhibited, mitochondrial function was impaired, and factors associated with the Pink1-Parkin pathway were inhibited. Acupotomy regulated the expression of Pink1-Parkin pathway-related proteins, the mitophagy-related protein microtubule-associated protein-1 light chain-3,the translocase of the outer membrane, and the inner mitochondrial membrane 23; increased the colocalization of mitochondria and autophagosomes; promoted the removal of damaged mitochondria;restored mitochondrial adenosine-triphosphate(ATP) production;and alleviated cartilage degeneration in rabbits with ***: Acupotomy played a role in alleviating KOA in rabbits by activating mitophagy in chondrocytes via the regulation of proteins that are related to the Pink1-Parkin pathway.

关键词： PTEN phosphohydrolase acupuncture therapy cartilage mitophagy osteoarthritis, knee

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Succinylation modification:a potential therapeutic target in stroke

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Neural Regeneration Research 2024年第4期19卷 781-787页

作者： Jie Lian Wenwu Liu Qin Hu Xiaohua Zhang Department of Neurosurgery Ren Ji HospitalShanghai Jiao Tong University School of Medicine Department of Diving and Hyperbaric Medicine Naval Medical CenterNaval Medical University

Stroke is a leading cause of mortality and disability *** cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain *** mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of ***,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ***,the role of succinylation modification in cell metabolism after stroke and its regulation are not well *** aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after *** also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of *** succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by *** evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic ***,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic *** between succinylation and desuccinylation has been implicated in the pathophysiology of *** agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke ***,their therapeutic efficacy in stroke patients should be validated.

关键词： mitochondria metabolism neuroprotection sirtuin 5 stroke succinylation modification

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In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke

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Neural Regeneration Research 2024年第10期19卷 2240-2248页

作者： Meng Yuan Yao Tang Tianwen Huang Lining Ke En Huang Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Human Anatomy School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Scientific Research Center School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Fujian Medical University Union HospitalFuzhouFujian ProvinceChina Fujian Key Laboratory of Vascular Aging Fujian Medical UniversityFuzhouFujian ProvinceChina

In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1(PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.e B-GFAP-sh PTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-sh PTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

关键词： astrocyte in situ direct reprogramming ischemic stroke miR-30 based shRNA neuron polypyrimidine tract-binding protein 1 transdifferentiation

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Increased N6-methyladenosine is related to the promotion of the methyltransferase METTL14 in ovarian aging

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Genes & Diseases 2024年第3期11卷 151-154页

作者： Chunfeng Qian Zhenxing Liu Yonghong Qian Jie Ding Rulei Chen Han Su Minghong Shen Hong Li Boxian Huang State Key Laboratory of Reproductive Medicine and Offspring Health Suzhou Affliated Hospital of Nanjing Medicine and Offspring HealthSuzhou Affiliated Hospital of Nanjing Medical UniversitySuzhouMunicipal HospitalGusu SchoolNanjing Medical UniversitySuzhouJiangsu 215002China Department of Gynecology Affliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu School of Nanjing Medical UniversitySuzhouJiangsu 215002China Department of Pathology Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu School of Nanjing Medical UniversitySuzhouJiangsu 215002China

The ovary is a vital female reproductive organ that functions to produce oocyte gametes and cyclically expressed sex hormones to maintain reproductive capacity and hormone *** aging,characterized by declines in follicle quantity and oocyte quality,leads to premature ovarian failure,premature ovarian insufficiency,or diminished ovarian reserve,thus contributing to female *** gene-expression signatures from RNA transcriptional level and post-transcriptional regulation are relative to oocyte quality and reproductive age.

关键词： promotion signature maintain

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Amide naphthotubes:Biomimetic macrocycles for selective molecular recognition

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Chinese Chemical Letters 2024年第4期35卷 124-131页

作者： Cheng-Da Zhao Huan Yao Shi-Yao Li Fangfang Du Li-Li Wang Liu-Pan Yang school of Pharmaceutical Science Postdoctoral Research Station of Basic MedicineHengyang Medical SchoolUniversity of South ChinaHengyang 421001China

Selective molecular recognition in water is routine for bioreceptors,but remains challenging for synthetic *** is principally because noncovalent interactions are usually less efficient in aqueous *** mimicking the cavity feature of bioreceptors,*** Jiang proposed and clarified the concept of“endo-functionalized cavity”.Through situating polar binding sites into a deep hydrophobic cavity,we designed and synthesized several macrocyclic hosts,among which amide naphthotubes are the most *** hosts can selectively recognize various polar molecules including organic micropollutants,drug molecules,and chiral molecules in water by employing the hydrophobic effect and shielded hydrogen *** addition,these biomimetic hosts have been applied in spectroscopic analysis,adsorptive separation and *** this review,we provide an overview of recent advances on amide naphthotubes with special emphasis on the efforts of Jiang's *** are convinced that these biomimetic macrocycles will make further contributions to supramolecular chemistry and beyond.

关键词： Molecular recognition Supramolecular chemistry Amide naphthotube Endo-functionalized cavity Biomimetic macrocycle

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DDAH1 promotes neurogenesis and neural repair in cerebral ischemia

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2097-2118页

作者： Qiming Gao Pinfei Ni Yilin Wang Peiyun Huo Xiaojie Zhang Sihan Wang Fuyao Xiao Yixuan Li Wei Feng Juntao Yuan Teng Zhang Qiang Li Boyu Fan Yuhao Kan Zhirui Li Yimiao Qi Junfei Xing Zhenghong Yang Haixiao Cheng Xinran Gao Xiaoyan Feng Ming Xue Yang Liu Yumin Luo Zhongbing Lu Yuming Zhao Department of Pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Cerebrovascular Diseases Research Institute and Department of Neurology Xuanwu Hospital of Capital Medical UniversityBeijing 100053China State Key Laboratory for Structural Chemistry of Unstable and Stable Species Institute of ChemistryChinese Academy of SciencesBeijing 100190China College of Life Science University of Chinese Academy of SciencesBeijing 100049China Department of Laboratory Animal School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Department of Physiology and Pathophysiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Choline acetyltransferase(ChAT)-positive neurons in neural stem cell(NSC)niches can evoke adult neurogenesis(AN)and restore impaired brain function after injury,such as acute ischemic stroke(AIS).However,the relevant mechanism by which ChAT+neurons develop in NSC niches is poorly *** RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1(DDAH1),a hydrolase for asymmetric NG,NG-dimethylarginine(ADMA),regulated genes responsible for the synthesis and transportation of acetylcholine(ACh)(Chat,Slc5a7 and Slc18a3)after stroke *** dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT,possibly through hypoxia-inducible factor 1α(HIF-1α).KC7F2,an inhibitor of HIF-1α,abolished DDAH1-induced ChAT expression and suppressed *** expected,DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS *** comparing the results among Ddah1 general knockout(KO)mice,transgenic(TG)mice and wild-type(WT)mice,we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone(SGZ)under ischemic *** a result,DDAH1 may promote cognitive and motor function recovery against stroke impairment,while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

关键词： DDAH1 Neurogenesis Neural repair ChAT HIF-1α ACh Stroke ADMA

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Aluminum exposure impairs oocyte quality via subcellular structure disruption and DNA damage-related apoptosis in mice

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Journal of Environmental Sciences 2024年第5期139卷 308-319页

作者： Hongge Li Jingcai Liu Weihua Nong Mengying Shen Sheng Dou Shaochen Sun Junli Wang The Affiliated Hospital of Youjiang medical university for Nationalities Guangxi 533000China College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China school of medical Laboratory Youjiang Medical University for NationalitiesGuangxi 533000China Industrial College of Biomedicine and Health Industry Youjiang Medical University for NationalitiesGuangxi 533000China Reproductive Medicine Guangxi Medical and Health Key Discipline Construction ProjectThe Affiliated Hospital of Youjiang Medical University for NationalitiesGuangxi 533000China

Aluminum(Al)can lead to an exposure of creature in varieties ways for its universality,and it could disturb normal physiological metabolism,with the damage to multisystem including *** the oocyte quality is critical for female reproduction,we inspected the toxicity of Al on mouse oocyte *** constructed in vitro exposure mouse model,and we found that 5 mmol/L Al had adverse effects on oocyte maturation by impairing organelle and *** spindle and misaligned chromosomes which might be considered to be caused by elevated levels of acetylation,as well as abnormal distribution of actin dynamics could hinder normal meiosis of *** dysfunction indicated that Al affected proteins synthesis,transport and digestion,which would further damage oocyte *** order to explore the mechanism of Al toxicity,our further investigation demonstrated that Al caused mitochondrial dysfunction and imbalance calcium homeostasis,resulting in limited energy ***,high level of reactive oxygen species,DNA damage and apoptosis caused by oxidative stress were also the manifestation of Al toxicity on *** conclusion,our study provided the evidence that Al exposure affected oocyte quality through its effects on spindle organization,actin dynamics,organelle function and the induction of DNA damage-related apoptosis with mouse model.

关键词： Aluminum Oocyte Cytoskeleton Organelle DNA damage

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Therapeutic effects of Coriandrum sativum extracts:A review

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 181-186页

作者： Akbar Anaeigoudari Department of Physiology School of MedicineJiroft University of Medical SciencesJiroftIran

Medicinal plants,as a good therapeutic strategy,can be used to treat a wide spectrum of *** sativum(***)is a plant from Apiaceae *** reports indicate that *** has positive effects on anxiety,seizure,learning and memory ability,as well as *** annual plant can also treat colitis,increase appetite,reduce blood pressure,and attenuate myocardial ***,it improves liver and kidney function and diabetes mellitus and inhibits osteoclast *** beneficial effects of *** mainly are attributed to its antioxidant and anti-inflammatory *** present paper reviews the impacts of *** on different body *** was extracted by searching the Web of Science,PubMed,Scopus,and Google Scholar from January 2010 until the end of February 2024.

关键词： Coriandrum sativum Inflammation Antioxidant Oxidative stress Nervous system Liver

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PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

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Oncology Research 2024年第6期32卷 1063-1078页

作者： KUN FENG HAO PENG QINGPENG LV YEWEI ZHANG Hepatopancreatobiliary Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210000China medical school Southeast UniversityNanjing210000China

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable *** dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment *** elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also ***,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of ***,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT *** findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer *** methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver ***,noteworthy associations were observed between PHLDA2 expression and immune infiltration in *** addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in *** vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy ***,we found that TGF-βinduced the expression of PHLDA2 in *** GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling *** study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

关键词： HCC Immune infiltration Drug resistance TME PHLDA2

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Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment

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Journal of Pharmaceutical Analysis 2024年第3期14卷 308-320页

作者： Mengxin Wang Stephen Vulcano Changlu Xu Renjian Xie Weijie Peng Jie Wang Qiaojun Liu Lee Jia Zhi Li Yumei Li Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province Gannan Medical UniversityGanzhouJiangxi341000China school of Rehabilitation Medicine Gannan Medical UniversityGanzhouJiangxi341000China Autoimmunity and Inflammation Program HSS Research InstituteHospital for Special Surgery New YorkNew YorkNY10021USA Division of Oral and Systemic Health Sciences School of DentistryUniversity of CaliforniaLos AngelesCA90095USA school of medical Information Engineering Gannan Medical UniversityGanzhouJiangxi341000China Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Institute of Innovative DrugsInstitute for Liver Diseases of Anhui Medical UniversitySchool of PharmacyAnhui Medical UniversityHefei230032China school of Basic Medicine Gannan Medical UniversityGanzhouJiangxi341000China Institute of Oceanography Minjiang UniversityFuzhou350108China

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced *** or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy *** data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to *** ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer *** correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well *** work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across *** plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

关键词： Ribosome biogenesis Ribosomopathy gene Cancer treatment target Pharmaceutical target

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