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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 *** diseases result from a deficiency of lysosomal enzymeβ-hexosaminidase A(HexA),which is responsible for GM2 ganglioside *** deficiency causes the accumulation of GM2-gangliosides mainly in the nervous system cells,leading to severe progressive neurodegeneration and *** date,there is no treatment for these ***-mediated gene therapy is considered a promising treatment for GM2 *** 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 *** effectiveness of HexA deficiency cross-correction was shown in mutant MSCs upon intera ction with *** 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 *** 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

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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 *** are considered a major health problem,as well as an economic and social problem,with potentially devastating and life-changing *** affect a wide range of patients with different damage mechanisms,varied depths,and localizations of the *** most common are thermal burns,with more than 11 million occurrences annually according to the World Health Organization *** 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 *** survivors face stress,anxiety,depression,low self-esteem,body deformity,social isolation,unemployment,financial burden,and family *** advances in acute burn care have allowed researchers and physicians to pay more attention to other effects of burns,focusing on psychological consequences in *** 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 *** 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

PCAF-mediated acetylation of METTL3 impairs mR NA translation efficiency in response to oxidative stress

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Science China Life Sciences 2024年

作者： Cheng Liu Miao Yu Mengyuan Wang Siyuan Yang Yenan Fu Lei Zhang Chaoyang Zhu Hongquan Zhang Program for Cancer and Cell Biology Department of Human Anatomy Histology and Embryology School of Basic Medical Sciences Peking University International Cancer Institute and State Key Laboratory of Molecular Oncology Peking University Health Science Center department of General Surgery and Urological Surgery Huaihe Hospital Henan University department of Human Anatomy Histology and Embryology Shenzhen University School of Medicine

METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase activity. METTL3 enhances RNA translation independently of its catalytic activity. However, the underlying mechanism is still elusive. Here, we report that METTL3 is both interacted with and acetylated at lysine 177 by the acetyltransferase PCAF and deacetylated by SIRT3. Neither the methyltransferase activity nor the stability of METTL3 is affected by its acetylation at K177. Importantly, acetylation of METTL3 blocks its interaction with EIF3H, a subunit of the translation initiation factor, thereby reducing mRNA translation efficiency. Interestingly, acetylation of METTL3 responds to oxidative stress. Mechanistically, oxidative stress enhances the interaction of PCAF with METTL3, increases METTL3 acetylation, and suppresses the interaction of METTL3 with EIF3H, thereby decreasing the translation efficiency of ribosomes and inhibiting cell proliferation. Altogether,we suggest a mechanism by which oxidative stress regulates RNA translation efficiency by the modulation of METTL3 acetylation mediated by PCAF.

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Evaluation of microRNA expression profiles in human sperm frozen using permeable cryoprotectant-free droplet vitrification and conventional methods

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Asian Journal of Andrology 2024年第4期26卷 366-376页

作者： Li-Xin Zhang Jing Mao Yan-Dong Zhou Guang-Yao Mao Run-Fa Guo Hong-Shan Ge Xia Chen department of histology and embryology Medical SchoolNantong UniversityNantong 226001China department of Reproductive Medicine The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou School of Clinical MedicineNanjing Medical UniversityTaizhou 225300China.

For sperm cryopreservation,the conventional method,which requires glycerol,has been used for a long *** addition,the permeable cryoprotectant-free vitrification method has been continuously *** the differences of cryopreservation effects between the two methods have being studied,differences in microRNA(miRNA)profiles between them remain *** this study,we investigated the differences in miRNA expression profiles among conventional freezing sperm,droplet vitrification freezing sperm and fresh human *** also analyzed the differences between these methods in terms of differentially expressed miRNAs(DEmiRs)related to early embryonic development and paternal *** results showed no significant differences between the cryopreservation methods in terms of sperm motility ratio,plasma membrane integrity,DNA integrity,mitochondrial membrane potential,acrosome integrity,and ultrastructural ***,sperm miRNA-sequencing showed differences between the two methods in terms of the numbers of DEmiRs(28 and 19 with vitrification using a nonpermeable cryoprotectant and the conventional method,respectively)in postthaw and fresh sperm *** related to early embryonic development and paternal epigenetics mainly included common DEmiRs between the *** results showed that the differences between conventional freezing and droplet vitrification were minimal in terms of miRNA expression related to embryonic development and *** in sperm miRNA expression due to freezing are not always detrimental to embryonic *** study compared differences in miRNA expression profiles before and after cryopreservation between cryopreservation by conventional and vitrification *** offers a new perspective to evaluate various methods of sperm cryopreservation.

关键词： cryopreservation cryoprotectant-free vitrification early embryonic development paternal epigenetic inheritance sperm miRNAs sucrose

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 *** 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 *** 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 *** review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and *** on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also *** 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

Lacidipine,thiamine pyrophosphate and their combination on the ocular ischemic syndrome induced by bilateral common carotid artery ligation

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 815-821页

作者： Ibrahim Cicek Ahmet Mehmet Somuncu Durdu Altuner Bahadir Suleyman Renad Mammadov Seval Bulut Taha Abdulkadir Coban Tugba Bal Tastan Halis Suleyman department of Ophthalmology Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey department of Pharmacology Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey department of Clinical Biochemistry Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey department of histology and embryology Faculty of MedicineErzincan Binali Yildirim University ErzincanErzincan 24100Turkey

AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in ***:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same *** anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the *** was created for 10min by placing clips on the right and left common carotid *** in the SG only underwent subcutaneous *** 10min,the clips were removed and reperfusion was achieved for six ***,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were *** retinal tissue of the eye was also examined ***:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in *** impact of these drugs on protection is determined to be LTC>lacidipine>***:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.

关键词： ocular ischemic syndrome lacidipine thiamine pyrophosphate oxidative stress

Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

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Neural Regeneration Research 2024年第11期19卷 2543-2552页

作者： Sam Enayati Karen Chang Anton Lennikov Menglu Yang Cherin Lee Ajay Ashok Farris Elzaridi Christina Yen Kasim Gunes Jia Xie Kin-Sang Cho Tor Paaske Utheim Dong Feng Chen Schepens Eye Research Institute of Massachusetts Eye and Ear Department of OphthalmologyHarvard Medical SchoolBostonMAUSA Institute of clinical medicine Faculty of MedicineUniversity of OsloOsloNorway department of Medical Biochemistry Oslo University HospitalUniversity of OsloOsloNorway department of Ophthalmology Drammen HospitalVestre Viken Hospital TrustDrammenNorway department of histology and embryology School of MedicineMarmara UniversityIstanbulTurkiye

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor *** research supports the beneficial effect of electrical stimulation on photoreceptor *** study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal ***,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem *** this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp *** investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with *** retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in *** density was evaluated by rhodopsin *** vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp *** function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),*** was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse *** recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest *** of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human *** tem

关键词： bipolar cells electrical stimulation neuroprotection photoreceptor degeneration retina retinal explants retinitis pigmentosa transcorneal electrical stimulation waveform

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

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han Tang Jianian Hu Siying Kang Song Qin department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

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 ***, 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 pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

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Long-Term Impact of Acute Retinoic Acid Supplementation at the Young Age on Testicular Architecture of Wistar Albino Rats

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Advances in Reproductive Sciences 2024年第1期12卷 1-13页

作者： Mama Sy Racha Kamenda Ibondou Fatoumata Bah Robert Foko Ndiaga Diop Mame Vénus Abdoulaye Séga Cheikh Diop Mamadou Fall Oumar Faye Laboratory of histology Embryology and Cytogenetics Faculty of Medecine Cheikh Anta Diop University Dakar Senegal

Introduction: Inappropriate and excess vitamin supplementation, particularly for vitamin A, is increasingly recognized as a public health problem in developed countries. On the other hand, blind supplementation of vitamin A, for children in developing countries is a subject of controversy in the literature. The crucial role of vitamin A in the process of spermatogenesis in adult rodents is well established, but only a few publications are consecrated to the long-term effect of vitamin A intake at a young age on testicular development and differentiation. Objectives: Our study aimed to evaluate the long-term effects of acute supplementation at an early age, in the post-natal period, on spermatogenesis and testicular trophicity at adult age. Material and Methods: Young Wistar Albinos rats of 22 days received an acute high dose of supplementation of vitamin A (retinyl palmitate). The control group, group 1, received only extra virgin olive oil, Group 2 a dose of 7000 IU/kg of retinyl palmitate, group 3, 14,000 IU/kg, and Group 4 a dose of 28,000 IU/kg. At 10 weeks of age, the testes’ testosterone levels were measured by ELISA. For histological assessment, sections were stained with Hematoxylin eosin, and the Johnsen score was used to evaluate spermatogenesis in the seminiferous tubules. Results: The average testicular weights of rats were significantly lower in group 4 (p < 0.05), and so was the testosterone level in the testis compared to the control group (p .01). Most of the seminiferous tubules were concerned by an arrest of spermatogenesis and the Johnsen score was decreased with a mean score of 5.96 ± 1.60 (p .001) in that Group. In Group 3, Johnsen’s score was significantly better than the one obtained with the control. Conclusion: We observed a negative effect in the long term with a high acute dose of supplementation of retinyl palmitate at a young age, on testicular development and differentiation. Despite a return to normal diet after that supplementation, d

关键词： Vitamin A Retinyl Palmitate Spermatogenesis Testis-Wistar Albino Rats