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Role of pituitary adenylate cyclase-activating polypeptide in peripheral nerve regeneration:a cellular and molecular perspective

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Neural Regeneration Research 2024年第7期19卷 1429-1430页

作者： Grazia Maugeri Velia D’Agata Section of anatomy Histology and Movement SciencesDepartment of Biomedical and Biotechnological SciencesUniversity of CataniaCataniaItaly

Neuro regeneration is a very complex phenomenon characterized by the generation of new neurons and synapses,involving connections between adjacent cells and axonal projections.Neuroregeneration supplies additional lon... 详细信息

关键词： replace functional regeneration

Increasingβ-hexosaminidase A activity using genetically modified mesenchymal stem cells

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Neural Regeneration Research 2024年第1期19卷 212-219页

作者： Alisa A.Shaimardanova Daria S.Chulpanova Valeriya V.Solovуeva Shaza S.Issa Aysilu I.Mullagulova Angelina A.Titova Yana O.Mukhamedshina Anna V.Timofeeva Alexander M.Aimaletdinov Islam R.Nigmetzyanov Albert A.Rizvanov Institute of Fundamental Medicine and Biology Kazan Federal UniversityKazanRussia department of histology Cytology and EmbryologyKazan State Medical UniversityKazanRussia

GM2 gangliosidoses are a group of autosomal-recessive lysosomal storage disorde rs.These diseases result from a deficiency of lysosomal enzymeβ-hexosaminidase A(HexA),which is responsible for GM2 ganglioside degradation.HexA deficiency causes the accumulation of GM2-gangliosides mainly in the nervous system cells,leading to severe progressive neurodegeneration and neuroinflammation.To date,there is no treatment for these diseases.Cell-mediated gene therapy is considered a promising treatment for GM2 gangliosidoses.This study aimed to evaluate the ability of genetically modified mesenchymal stem cells(MSCs-HEXA-HEXB)to restore HexA deficiency in Tay-Sachs disease patient cells,as well as to analyze the functionality and biodistribution of MSCs in vivo.The effectiveness of HexA deficiency cross-correction was shown in mutant MSCs upon intera ction with MSCs-HEXA-HEXB.The results also showed that the MSCs-HEXA-HEXB express the functionally active HexA enzyme,detectable in vivo,and intravenous injection of the cells does not cause an immune response in animals.These data suggest that genetically modified mesenchymal stem cells have the potentials to treat GM2 gangliosidoses.

关键词： adeno-associated viral vectors cell therapy cell-mediated gene therapy gene therapy GM2 gangliosidosis Sandhoff disease Tay-Sachs disease β-hexosaminidase

Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong department of Neurology of the Second Afliated Hospital and department of Human anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China department of Physiology and department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of Human Reproduction and Developmental Genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral Sclerosis.In a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into fibrils.Cellular and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent years.This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and secretion.Debates on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also discussed.Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

Therapeutic approach to emotional reactions accompanied with thermal skin injury–from basic to epidemiological research

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World Journal of Psychiatry 2024年第2期14卷 199-203页

作者： Bojana Krstic Milos Krstic Dragica Selakovic Nemanja Jovicic Gvozden Rosic department of Physiology Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia department of histology and embryology Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia

In this editorial,we discuss the status of a therapeutic approach to emotional reactions accompanying thermal skin injuries.Burns are considered a major health problem,as well as an economic and social problem,with potentially devastating and life-changing consequences.They affect a wide range of patients with different damage mechanisms,varied depths,and localizations of the burns.The most common are thermal burns,with more than 11 million occurrences annually according to the World Health Organization data.Thermal skin injuries are among the most tragic and catastrophic injuries,almost unsurpassed in terms of severity,morbidity,and mortality,as well as functional,aesthetic,social,economic,and psychological consequences.Burn survivors face stress,anxiety,depression,low self-esteem,body deformity,social isolation,unemployment,financial burden,and family problems.The advances in acute burn care have allowed researchers and physicians to pay more attention to other effects of burns,focusing on psychological consequences in particular.Apart from the significant improvements in routine protocols,it seems useful to take care of psychological disturbances that occur simultaneously but may emerge as the most lasting outcome of those injuries.In that sense,various standards and additional approaches may be involved to achieve overall recovery.

关键词： Thermal skin injury Anxiety Depression Psychological consequences of burns

Protein expression profile in the differentiation of rat bone marrow stromal cells into Schwann cell-like cells

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Science China(Life Sciences) 2009年第3期52卷 267-277页

作者： LI WenTing1,SUN HuaLin2,XU ZengLu1,DING Fei2 & GU XiaoSong2 1 department of anatomy,histology and embryology,Peking Union Medical College,Institute of Basic Medical Science,Chinese Academy of Medical Sciences,Beijing 100005,China 2 Jiangsu Key Laboratory of Neuroregeneration,Nantong University,Nantong 226001,China department of anatomy Histology and Embryology Peking Union Medical College Institute of Basic Medical Science Chinese Academy of Medical Sciences Beijing China Jiangsu Key Laboratory of Neuroregeneration Nantong University Nantong China

During the last decade,increasing evidence suggested that bone marrow stromal cells(MSCs) have the potential to differentiate into neural lineages.Many studies have reported that MSCs showed morphological changes and expressed a limited number of neural proteins under experimental conditions.However,no proteomic studies on MSCs differentiated into Schwann cell-like cells have been reported.In this study,we isolated MSCs from adult Sprague-Dawley rat femur and tibia bone marrows and induced the cells in vitro under specific conditions.By using two-dimensional gel electrophoresis(2-DE),we compared the protein profiles of MSCs before and after induced differentiation.We obtained 792 protein spots in the protein profile by 2-DE,and found that 74 spots changed significantly before and after the differentiation using PDQuest software,with 43 up-regulated and 31 down-regulated.We analyzed these 74 spots by a matrix assisted laser desorption ionization-time of flight mass spectrometry(MALDI-TOF-MS) and by database searching,and found that they could be grouped into various classes,including cytoskeleton and structure proteins,growth factors,metabolic proteins,chaperone proteins,receptor proteins,cell cycle proteins,calcium binding proteins,and other proteins.These proteins also include neural and glial proteins,such as BDNF,CNTF and GFAP.The results may provide valuable proteomic information about the differentiation of MSCs into Schwann cell-like cells.

关键词： one marrow stromal cells(MSCs) differentiation Schwann cell-like cells proteomics

Effect of Combination Regimen of Low-dose Gossypol Acetic Acid with Steroid Hormones on Expression of Protein Kinase C alpha (PKC-α) and Cyclin D1 in Rat Testes

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Journal of Reproduction and Contraception 2012年第4期23卷 199-208页

作者： Jin-hui SHAO Zeng-lu XU Xiao-jing QIAN Fang LIU Hui HUANG department of anatomy Histology and Embryology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College department of histology and embryology School of Medicine Hubei University of Art and Science

Objective To investigate the contraceptive mechanism of combination regimen of low- dose gossypol acetic acid （GA） with steroid hormones [desogestre/ethinylestradiol/ testosterone undeeanote（DSG/EE/TU）]. Methods Adult male rats were randomly divided into four groups. Group GH： rats were fed orally with gossypol acetic acid （GA, 12.5 mg/kg） and desogestrel （DSG, 0.125 mg/kg）/ ethinylestradiol （EE, 0.025 mg/kg）/testosterone undecanoate （TU, 100 mg/kg per day, qd X4 weeks or 10 weeks）; group G： a single dose of GA （12.5 mg/kg per day, qd X 4 weeks or I0 weeks）; group H： the same dosage of DSG/EE/TUas in group GH; group C： rats were treated with vehicle （1% methyl cellulose） as the control. Expression of protein kinase C alpha （PKC-a） and cyclin D1 in rat testes were tested mainly by immunohistochemistry （IHC） and Western blotting. Results IHC results showed that protein PKC- a was expressed mainly in interstitial tissue of testis among seminiferous tubule. The expression of PKC-oc in groups H and GH at week 10 was decreased greatly compared with that in group C. The protein cyclin D1 was expressed mainly in residual body of seminiferous tubule eavosurface and interstitial tissue among seminiferous tubule of testis. Western blotting results showed that the expression of PKC-a in groups H and GH at week 10 was decreased significantly compared with that in group C （P〈0.05）. The expression of cyclin D1 in groups G, H or GH at week 10 rose significantly compared with that in group C （P 〈0.05）.Conclusion The administration of low-dose gossypol acetic acid with steroid hormones for 10 weeks can decrease the expression of PKC-a greatly.

关键词： gossypol steroid hormones protein kinase C alpha （PKC-a） cyclin D 1 rat testes

Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期 1599-1612页

作者： Guibo Qi Han Tang Jianian Hu Siying Kang Song Qin department of anatomy Histology and Embryology School of Basic Medical Sciences Fudan University State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan University

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier function.However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeuti

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A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2025年第2期20卷 503-517页

作者： Qi Liu Jianye Xie Runxue Zhou Jin Deng Weihong Nie Shuwei Sun Haiping Wang Chunying Shi department of Human anatomy Histology and EmbryologySchool of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina department of Neurology The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina department of General Practice The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

关键词： angiogenesis biomaterial blood-brain barrier cerebral ischemia/reperfusion injury control release drug delivery inflammation QK peptides matrix metalloproteinase-2 neuroprotection self-assembling nanofiber hydrogel

A quantification model for apoptosis in mouse embryos in the early stage of fetation

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Science China(Life Sciences) 2009年第10期52卷 922-927页

作者： WANG PengFei1, FU JianHua1, MA WanYun1, CHEN DieYan1, Lü DanYu2 & BAI WenJia3 1 Key Laboratory for Atomic and Molecular Nanosciences of Education Ministry, department of Physics, Tsinghua University, Beijing 100084, China 2 department of anatomy & histology and embryology, School of Basic Medical Sciences Peking University Health Science Center, Beijing 100083, China 3 department of Automation, Tsinghua University, Beijing 100084, China Key Laboratory for Atomic and Molecular Nanosciences of Education Ministry Department of Physics Tsinghua University Beijing China department of anatomy & histology and embryology School of Basic Medical Sciences Peking University Health Science Center Beijing China department of Automation Tsinghua University Beijing China

Apoptosis is the most important inducement and modulator for embryos in the early stage of fetation, i.e. after the 8-cell stage, mostly the morula and blastula stage, to proceed to the stage of nonlinear development. Using a two-photon laser scanning microscopy (TPLSM) system, we obtained 3-dimensional (3D) fluorescent images of preimplantation mouse embryos. A model for quantification was established. The statistical results for the spatial location of apoptosis bodies in embryos was obtained following image processing, as well as investigation of the kinetics of apoptosis. It was found that most (70%) apoptosis occurred in the trophectoderm, and the departure between the centroid and geometric center of embryos had a step transition when embryos developed into the 32-cell stage, which was consistent with the theoretical prediction that the blastocele would induce a symmetry break of the distribution of cells in embryos.

关键词： apoptosis preimplantation mouse embryo TPLSM quantification model