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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

Pre-activated macrophage membrane-encased aggregationinduced emission featuring nanoparticles:a novel possibility for tuberculosis treatment

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2848-2850页

作者： Qiang Cai Yihao Tian Quazi T.H.Shubhra department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanChina department of Human Anatomy and histology and embryology School of Basic Medical SciencesWuhan UniversityWuhanChina Institute of Chemistry University of Silesia in KatowiceSzkolna 9KatowicePoland

In a recent study published in Nature Nanotechnology,Li et *** the synthesis of a novel photosensitizer with unique aggregation-induced emission(AIE)characteristics.1 They microencapsulated this photosensitizer inside engineered nanoparticles(NPs)coated with pre-activated macrophage cell membranes(CMs),an innovative approach marking a significant leap in nanomedicine by offering a pathway to potent tuberculosis(TB)treatments that bypass antibiotic resistance with unparalleled precision.

关键词： tuberculosis macrophage aggregation

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

Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

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Military medical Research 2024年第4期 500-520页

作者： Kun Zhang Meng-Xia Zhang Xiao-Xiang Meng Jing Zhu Jia-Jun Wang Yi-Fan He Ye-Hua Li Si-Cong Zhao Zhe-Min Shi Li-Na Zheng Tao Han Wei Hong department of histology and embryology School of Basic Medical Sciences Tianjin Medical University department of Hepatology and Gastroenterology Tianjin Union Medical Center Tianjin Medical University Tianjin Union Medical Center Affiliated to Nankai University

Background: G-protein coupled receptors（GPCRs） are recognized as attractive targets for drug therapy. However, it remains poorly understood how GPCRs, except for a few chemokine receptors, regulate the progression of liver fibrosis. Here, we aimed to reveal the role of GPR65, a proton-sensing receptor, in liver fibrosis and to elucidate the underlying ***: The expression level of GPR65 was evaluated in both human and mouse fibrotic livers. Furthermore, Gpr65-deficient mice were treated with either bile duct ligation（BDL） for 21 d or carbon tetrachloride（CCl4） for 8 weeks to investigate the role of GPR65 in liver fibrosis. A combination of experimental approaches, including Western blotting, quantitative real-time reverse transcription-polymerase chain reaction（qRT-PCR）, and enzyme-linked immunosorbent assay（ELISA）, confocal microscopy and rescue studies, were used to explore the underlying mechanisms of GPR65's action in liver fibrosis. Additionally, the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was ***: We found that hepatic macrophage（HM）-enriched GPR65 was upregulated in both human and mouse fibrotic livers. Moreover, knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation, injury and fibrosis in vivo, and mouse bone marrow transplantation（BMT） experiments further demonstrated that the protective effect of Gpr65 knockout is primarily mediated by bone marrow-derived macrophages（BMMs）. Additionally, in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited, while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α（TNF-ivationα）, interleukin-6（IL-6） and transforming growth factor-of hepatic stellate cells（HSCs） and the damage of hepaβ（TGF-tocytes β）, all of which subsequently promoted the act（HCs）. Mechanistically, GPR65 overexpression, the acidic pH and GPR65 exo

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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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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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YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation

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Research 2024年第2期6卷 401-415页

作者： Jiadi Lv Xiaohan Liu Yabo Zhou Feiran Cheng Haoran Chen Shunshun Li Dianheng Wang Li Zhou Zhenfeng Wang Nannan Zhou Jie Chen Bo Huang department of Immunology&State Key Laboratory of Common Mechanism Research for Major Diseases Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical College(PUMC)Beijing100005China department of histology and embryology Basic Medical CllegeChina Medical UniversityShenyangLiaoning 11122China department of Immunology Basic Medical Cllege China Medical UniversityShenyangLiaoning 110122China department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China

Solid tumor cells live in a highly dynamic mechanical *** the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an ***,we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like ***,integrin?was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein(YAP).YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G(MAFG),allowing MAFG to transactivate the stemness genes NANOG,SOX2,and *** also restoredβ8 expression,thereby forming a closed mechanical ***,MAFG expression is correlated with worse *** findings provide mechanical insights into the regulation of tumor cell dedifferentiation,which has therapeutic implications for exploring innovative strategies to attack malignancies.

关键词： activation thereby MAF