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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

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

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Science China(Life Sciences) 2024年第10期67卷 2157-2168页

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 AnatomyHistology and EmbryologySchool of Basic Medical SciencesPeking University International Cancer Instituteand State Key Laboratory of Molecular OncologyPeking University Health Science CenterBeijing 100191China department of General Surgery and Urological Surgery Huaihe HospitalHenan UniversityKaifeng 100084China department of Human Anatomy Histologyand EmbryologyShenzhen University School of MedicineShenzhen 518055China

METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase ***3 enhances RNA translation independently of its catalytic ***,the underlying mechanism is still ***,we report that METTL3 is both interacted with and acetylated at lysine 177 by the acetyltransferase PCAF and deacetylated by *** the methyltransferase activity nor the stability of METTL3 is affected by its acetylation at ***,acetylation of METTL3 blocks its interaction with EIF3H,a subunit of the translation initiation factor,thereby reducing mRNA translation ***,acetylation of METTL3 responds to oxidative ***,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 ***,we suggest a mechanism by which oxidative stress regulates RNA translation efficiency by the modulation of METTL3 acetylation mediated by PCAF.

关键词： METTL3 acetylation PCAF m^(6)A oxidative stress translation SIRT3

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

Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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Neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： Krisztián Pajer Tamás Bellák Antal Nógrádi department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

关键词： injured capacity modified

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

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11卷 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 SciencesTianjin Medical UniversityTianjin 300070China department of Hepatology and Gastroenterology Tianjin Union Medical CenterTianjin Medical UniversityTianjin Union Medical Center Affiliated to Nankai UniversityTianjin 300000China

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug ***,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver ***,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 ***,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 ***,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 ***,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 Gpr65knockout 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-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of

关键词： GPR65 Hepatic fibrosis Hepatic macrophages Inflammation c-Jun N-terminal kinase Nuclear factorκB

Intestinal glucagon-like peptide-1:A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic mice

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World Journal of Diabetes 2024年第8期15卷 1764-1777页

作者： Fang-Xin Jin Yan Wang Min-Ne Li Ru-Jiang Li Jun-Tang Guo department of histology and embryology Key Laboratory of Universities in Shandong ProvinceShandong Second Medical UniversityWeifang 261053Shandong ProvinceChina department of Pathological Physiology Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina

BACKGROUND Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic ***,the pathogenesis of hypoglycaemic counterregulation is still ***-like peptide-1(GLP-1)and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus(T1DM).The role of GLP-1 in counterregulatory dysfunction during hypoglycaemia in patients with T1DM has not been *** To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic *** T1DM was induced in C57BL/6J mice using streptozotocin,followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia(DH5).Immunofluorescence,Western blot,and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon(GCG)*** GLP-1 receptor agonist GLP-1(7-36)or the antagonist exendin(9-39)were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model *** The expression levels of intestinal GLP-1 and its receptor(GLP-1R)were significantly increased in DH5 *** instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex,leading to dysfunction of adrenal counterregulation during ***5 mice showed increased pancreaticδ-cell mass,cAMP levels inδcells,and plasma somatostatin concentrations,while cAMP levels in pancreaticαcells and plasma GCG levels ***,GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 *** experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstra

关键词： Glucagon-like peptide-1 Impaired hypoglycaemic counterregulation Type 1 diabetes Intestine Pancreas

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

Exploring hematopoietic stem cell population in human milk and its benefits for infants:A scoping review

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Asian pacific Journal of Reproduction 2024年第3期13卷 107-114,I0001-I0006页

作者： Ghaniyyatul Khudri Dewi Sukmawati department of histology Faculty of MedicineUniversitas BaiturrahmahPadangIndonesia department of histology Faculty of MedicineUniversitas IndonesiaJakartaIndonesia

Objective:To comprehensively explore hematopoietic stem cells(HSCs)in human milk,understanding their molecular markers,isolation methods,benefits for infants,and potential medical ***:We conducted a scoping literature review following the PRISMA-ScR *** review included studies investigating HSCs in human milk,utilizing molecular markers such as CD34^(+),CD113^(+),and CD117^(+)for *** in vitro and in vivo studies exploring the morphology,function,and clinical implications of these cells were *** diverse range of papers reviewed were indexed in PubMed,Science Direct,Scopus,Sage Journals,and Google Scholar,published between 2010 and ***:This scoping review explored 577 articles and selected 13 studies based on our inclusion criteria,focusing on HSCs in human *** studies dilute samples prior to HSC isolation,followed by detection using markers such as CD34^(+),CD113^(+),and CD117^(+),with flow cytometry serving as the primary analysis tool,focusing on their isolation and detection *** no definitive benefits have been conclusively established,there is a strong belief in the potential of HSCs to positively impact infant immunity,growth,and tissue ***:This review presents significant evidence supporting the presence of HSCs in human milk,identified by markers such as CD34^(+),CD113^(+),and CD117^(+).These cells show considerable potential in enhancing infant health,including immunity,tissue repair,cognitive development,and gastrointestinal *** methodological variations in isolation and detection techniques,the collective findings underscore the potential clinical relevance of HSCs in human ***,this review highlights the noninvasive accessibility of human milk as a source of HSCs and emphasizes the need for further research to unlock their therapeutic potential.

关键词： CD34^(+) Cellular components Hematopoietic stem cells Human milk Stem cells