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Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

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Neural Regeneration Research 2025年第8期20卷 2169-2180页

作者： Mingyi Yu Faith Teo En Ning Chang Liu Yu-Chi Liu Tissue Engineering and stem cell Group Singapore Eye Research InstituteSingapore Yong Loo Lin School of Medicine National University of SingaporeSingapore Department of Cornea and External Eye Disease Singapore National Eye CenterSingapore Ophthalmology and Visual Sciences Academic Clinical Program Duke-NUS Medical SchoolSingapore

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes *** corneal neuropathy refers to the progressive damage of corneal *** retinopathy has traditionally been considered as damage to the retinal ***,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural *** retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular ***,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface *** studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic *** review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal *** also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

关键词： cornea corneal nerves diabetes diabetic corneal neuropathy diabetic retinopathy retina

Comparison of efficacy between HLA6/6-and HLA3/6-matched haploidentical hematopoietic stem cell transplant in T-cell-replete transplants between parents and children

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Science China(Life Sciences) 2019年第1期62卷 104-111页

作者： Wenjing Yu Yu Wang Depei Wu Qifa Liu Lanping Xu Xiaohui Zhang Kaiyan Liu Xiaojun Huang Peking University People's Hospital Peking University Institute of Hematology Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation The First Affiliated Hospital of Soochow University Nanfang Hospital Southern Medical University Peking-Tsinghua Center for Life Sciences

To compare the efficacy of HLA6/6-matched haploidentical hematopoietic stem cell transplant(haplo-HSCT) with that of HLA3/6-matched HSCT in T-cell-replete transplants, we recruited 27 consecutive recipients from multiple centers who received HLA6/6-matched haplo-HSCT from a parent or child donor between February 2010 and May 2016. A matched-pair analysis was designed. For each recipient from the study cohort, two recipients were randomly selected from the control cohort and matched(according to patient age, patient sex, disease type, disease status, donor age, donor sex, and recipient-donor relationship). No significant differences were found in hematopoietic recovery. The incidence of grade II–IV and III–IV acute graft versus host disease was similar(18.5% vs. 31.5%, P=0.216; 11.1% vs. 9.3%, P=0.792) in the HLA6/6 and HLA3/6 groups, respectively. The3-year cumulative incidence of relapse was 14.8% and 17.0%(P=0.800). The 3-year cumulative incidence of nonrelapse mortality was 12.1% and 17.6%(P=0.751). The estimated 3-year disease-free survival was 73.1% and 65.5%(P=0.489). The estimated 3-year overall survival was 74.7% and 74.0%(P=0.946). The data suggested the efficacy and safety of the HLA6/6-and the HLA3/6-matched haplo-HSCT between parents and children are comparable. That HLA-mismatch disparity is not correlated with T-cell-replete haplo-HSCT outcome was substantiated.

关键词： donor human leukocyte antigen hematopoietic stem cell transplantation

Role of Lef1 in sustaining self-renewal in mouse embryonic stem cells

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Journal of Genetics and Genomics 2010年第7期37卷 441-449页

作者： Chen Huang Dajiang Qin stem cell and Cancer biology Group Key Laboratory of Regenerative Biology South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510530 China

Embryonic stem cells （ESCs） can self-renew indefinitely while maintaining the ability to generate all three germ-layer *** the importance of ESCs in developmental biology and their potential impact on regenerative medicine,the molecular mechanisms controlling ESC behavior are incompletely ***,activation of the canonical Wnt signaling pathway has been shown to contribute to mouse ESC *** we report that ectopic expression of Lef1,a component of the Wnt signaling pathway,has a positive effect on the self-renewal of mouse ***1 up-regulates Oct4 promoter activity and physically interacts with Nanog,two key components of the ESC pluripotency ***,siRNA for Lef1 induced mouse ESC *** results thus suggest that in response to Wnt signaling Lef1 binds to stabilized β-catenin and helps maintain the undifferentiated status of ESCs through modulation of Oct4 and Nanog.

关键词： embryonic stem cells Wnt signaling 13-catenin Lefl Oct4 Nanog

Functional analysis of two Sp1/Sp3 binding sites in murine Nanog gene promoter

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cell Research 2006年第3期16卷 319-322页

作者： Da Yong Wu Zhen Yao Laboratory of Molecular cell biology,Laboratory of stem cell biology,Institute of Biochemistry and cell biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences 320 Yue Yang Road,Shanghai 200031,China Laboratory of Molecular cell biology Laboratory of Stem Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Nanog gene plays a key role in maintaining pluripotency of ES cells and early embryonic cells.A 5’ flank sequenceof the Nanog gene has been reported to be regulated differentially,and two regulatory elements within the Nanog pro-moter,namely Oct-4 and Sox-2 binding sites,have been identified to regulate the transcriptional activity ofNanog *** this report,we identified the role of two putative Sp 1 binding sites located in the Nanog gene 5’-flanking region inregulation of murine Nanog gene *** studies showed that the two sites were essential for the Nanogpromoter *** shift and supershift analysis showed that both sites specifically bind Spl and ***,overexpression of dominant-negative Sp 1 or Sp3 mutants significantly inhibits Nanog promoter *** resultssuggest that the transcription factor Spl and Sp3 are important for Murine Nanog gene expression.

关键词： Nanog promoter Sp1 Sp3

A highly efficient method for enriching TALEN or CRISPR/Cas9-edited mutant cells

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Journal of Genetics and Genomics 2016年第12期43卷 705-708页

作者： Hideyo Yasuda Eunsu Kim Abu Musa Md Talimur Reza Jin-Hoi Kim Department of stem cell and Regenerative biology Konkuk University

In recent years,genome editing with site-specific nucleases,such as ZFN（zinc finger nuclease）,TALEN（transcription activatorlike effector nucleases）,and CRISPR/Cas9（the type II bacterial clustered,regularly interspaced,short palindromic repeats-associated protein 9）,has gained popularity for use in cell lines,animals,and plants（Urnov et al.,2010;Miller et al.,2011;Cong et al.

关键词： A highly efficient method for enriching TALEN or CRISPR/Cas9-edited mutant cells gene DNA RNA ZFN

PIWI proteins and their interactors in piRNA biogenesis,germline development and gene expression

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National Science Review 2014年第2期1卷 205-218页

作者： Hsueh-Yen Ku Haifan Lin Yale stem cell Center and Department of cell biology Yale University School of Medicine

PIWI-interacting RNAs(piRNAs) are a complex class of small non-coding RNAs that are mostly 24–32nucleotides in length and composed of at least hundreds of thousands of species that speciically interact with the PIWI protein subfamily of the ARGONAUTE family. Recent studies revealed that PIWI proteins interact with a number of proteins, especially the TUDOR-domain-containing proteins, to regulate piRNA biogenesis and regulatory function. Current research also provides evidence that PIWI proteins and pi RNAs are not only crucial for transposon silencing in the germline, but also mediate novel mechanisms of epigenetic programming, DNA rearrangements, m RNA turnover, and translational control both in the germline and in the soma. hese new discoveries begin to reveal an exciting new dimension of gene regulation in the cell.

关键词： PIWI piRNA TDRD epigenetic RNA decay translational regulation

Anti-Tumor Immunology in BMT:Separating Graft versus Leukemia from Graft versus Host Disease

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中国实用内科杂志 2007年第S1期27卷 1-8页

作者： Ned Waller Bone Marrow and stem cell transplant Center Emory University

Regeneration of the central nervous system-principles from brain regeneration in adult zebrafish

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World Journal of stem cells 2020年第1期12卷 8-24页

作者： Alessandro Zambusi Jovica Ninkovic Helmholtz Center Munich Biomedical CenterInst Stem Cell ResInstitute of Stem Cell ResearchDepartment of Cell Biology and AnatomyUniversity of Munich

Poor recovery of neuronal functions is one of the most common healthcare challenges for patients with different types of brain injuries and/or neurodegenerative *** interventions face two major challenges:(1)How to generate neurons de novo to replenish the neuronal loss caused by injuries or neurodegeneration(restorative neurogenesis)and(2)How to prevent or limit the secondary tissue damage caused by long-term accumulation of glial cells,including microglia,at injury site(glial scar).In contrast to mammals,zebrafish have extensive regenerative capacity in numerous vital organs,including the brain,thus making them a valuable model to improve the existing therapeutic approaches for human brain *** response to injuries to the central nervous system(CNS),zebrafish have developed specific mechanisms to promote the recovery of the lost tissue architecture and functionality of the damaged *** mechanisms include the activation of a restorative neurogenic program in a specific set of glial cells(ependymoglia)and the resolution of both the glial scar and inflammation,thus enabling proper neuronal specification and *** this review,we discuss the cellular and molecular mechanisms underlying the regenerative ability in the adult zebrafish brain and conclude with the potential applicability of these mechanisms in repair of the mammalian CNS.

关键词： Zebrafish Central nervous system Brain injury Glial scar Regeneration Restorative neurogenesis Neural stem cells Inflammation

Comparable anti-CMV responses of transplant donor and third-party CMV-specific T cells for treatment of CMV infection after allogeneic stem cell transplantation

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cellular & Molecular Immunology 2022年第4期19卷 482-491页

作者： Xu-Ying Pei Xue-Fei Liu Xiang-Yu Zhao Meng Lv Xiao-Dong Mo Ying-Jun Chang Qian-Nan Shang Yu-Qian Sun Yu-Hong Chen Lan-Ping Xu Yu Wang Xiao-Hui Zhang Kai-Yan Liu Xiao-Jun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing100044China Peking-Tsinghua Center for Life Sciences Beijing100871China

Adoptive transfer of cytomegalovirus(CMV)-specific cytotoxic T lymphocytes(CMV-CTLs)from original transplant donors or third-party donors was effective for the treatment of CMV infection after allogenic stem cell transplantation(allo-SCT),but the antiviral activity of CMV-CTL types has not been *** determine whether third-party CMV-CTLs provide comparable long-term antiviral efficacy to transplant donor CMV-CTLs,we first compared the antiviral abilities of transplant donors and third-party CMV-CTLs for treatment of CMV infection in two mouse models,compared the in vivo recovery of CMV-specific immunity,and analyzed the underlying mechanisms driving sustained antiviral *** results showed that both donor and third-party CMV-CTLs effectively combated systemic CMV infection by reducing CMV pathology and tumor burden 28 days *** in vivo recovery of CMV-specific immunity after CMV-CTL infusion was comparable in both groups.A detailed analysis of the source of recovered CMV-CTLs showed the proliferation and expansion of graft-derived endogenous CMV-CTLs in both *** clinical study,which enrolled 31 patients who received third-party CMV-CTLs and 62 matched pairs of individuals who received transplant donor CMV-CTLs for refractory CMV infection,further showed that adoptive therapy with donor or third-party CMV-CTLs had comparable clinical responses without significant therapy-related *** observed strong expansion of CD8+tetramer+T cells and proliferation of recipient endogenous CMV-CTLs after CMV-CTL infusion,which were associated with a reduced or cleared viral *** data confirmed that adoptive therapy with third-party or transplant donor CMV-CTLs triggered comparable antiviral responses to CMV infection that might be mediated by restoration of endogenous CMV-specific immunity.

关键词： Allogeneic stem cell transplantation CMV-specific cytotoxic T lymphocytes transplant donor Third party donor Immunotherapy