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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

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Red cell distribution width/platelet ratio predicts decompensation of metabolic dysfunction-associated steatotic liver disease-related compensated advanced chronic liver disease

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World Journal of Gastroenterology 2025年第3期31卷 1-10页

作者： Ming-Hua Zheng Amedeo Lonardo Department of Hepatology MAFLD Research CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Internal Medicine Azienda Ospedaliero-Universitaria of Modena(2023)Modena 41126Italy

Prognostication of compensated advanced chronic liver disease(cACLD)is of paramount importance for the physician-and-patient communication and for rational clinical *** paper published by Dallio et al reports on red cell distribution width(RDW)/platelet ratio(RPR)as a non-invasive biomarker in predicting decompensation of metabolic dysfunction-associated steatotic liver disease(MASLD)-related *** from other biomarkers and algorithms,RPR is inexpensive and widely available,based on parameters which are included in a complete blood *** is computed on the grounds of two different items,one of which,RDW,mirrors the host’s response to a variety of disease stimuli and is *** second parameter involved in RPR,platelet count,is more specific and has been used in the hepatological clinic to discriminate cirrhotic from non-cirrhotic chronic liver disease for *** disease is the primary cause of mortality among MASLD subjects,followed by extra-hepatic cancers and liver-related ***,MASLD biomarkers should be validated not only in terms of liver-related events but also in the prediction of major adverse cardiovascular events and cardiovascular mortality and extra-hepatic *** sized multi-ethnic confirmatory investigation is required to define the role and significance of RPR in the stratification of MASLD-cACLD.

关键词： Cirrhosis Liver fibrosis Natural course Prognostication Stratification

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FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

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Neural Regeneration Research 2025年第7期20卷 2068-2083页

作者： Jing Yao Yuan Li Xi Liu Wenping Liang Yu Li Liyong Wu Zhe Wang Weihong Song The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Pediatrics The Second Affiliated Hospital and Yuying Children’s HospitalKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang ProvinceChina Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine Visionand Brain Health)WenzhouZhejiang ProvinceChina

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the *** NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and *** NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory ***,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau *** biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in *** primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis *** the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical *** analysis suggested that FUBP3 plays a role in neuron-mediated immune *** also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced *** findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in *** that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

关键词： 5′end trimming Alzheimer's disease amyloid-beta amyloid-β-dependent transcription FUBP3 inflammasome inflammation neuron NLRP3 tau transcription factor

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Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

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Neural Regeneration Research 2025年第4期20卷 946-959页

作者： Zhiyuan Yin Jiahui Kang Xuan Cheng Hui Gao Shujia Huo Haiwei Xu Key Lab of Visual Damage and Regeneration&Restoration of Chongqing Southwest Eye HospitalSouthwest HospitalThird Military Medical University(Army Medical University)ChongqingChina

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased *** lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored ***,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various *** in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in ***,there remain issues that hinder improving reprogramming efficiency and ***,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming *** review describes recent progress in relatively successful Müller glia reprogramming *** also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

关键词： cell fusion chemical small-molecules epigenetic extracellular matrix immune metabolic mice Müller glia neurodegenerative diseases reprogramming retina regeneration

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The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

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Neural Regeneration Research 2025年第10期20卷 2741-2757页

作者： Qianzi Jin Suyu Wang Yujia Yao Qin Jiang Keran Li Department of Ophthalmology The Affiliated Eye Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina The Fourth School of Clinical Medicine Nanjing Medical UniversityNanjingJiangsu ProvinceChina

Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts ***,the specific pathogenesis remains unclear,and effective early treatment options are consequently *** microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a *** intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other *** dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many *** recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the ***,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s ***,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular ***,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable *** such,the intestinal flora may play an important role in age-related macular *** the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic ***,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular ***-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the inte

关键词： age-related macular degeneration biological agents blinding eye disease dietary nutrition fecal microbial transplantation gut-eye axis intestinal flora metabolite microecology neurodegenerative disease

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Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration Research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei Henan eye hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina eye Institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of National Clinical Research Center for Ocular Disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

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Effects of baffie and intraocular pressure on aerosols generated in the noncontact tonometer measurement during COVID-19

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International Journal of Ophthalmology(English edition) 2022年第4期15卷 533-540页

作者： Yuan Tang Yan-Yan Chen Chun-Chun Li Zhang-Yan Chen Chen Chen Si-Qi Wen Xiao-Qiong Huang Jia Qu Yan-Miao Chen Ai-Ai Chen The eye hospital Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina the affiliated ningbo eye hospital of wenzhou medical university Ningbo 315000Zhejiang ProvinceChina

AIM: To investigate the effects of baffle and intraocular pressure(IOP) on the aerosols generated in the noncontact tonometer(NCT) measurement and provide recommendations for the standardized use of the NCT during coronavirus disease 2019(COVID-19). METHODS: This clinical trial included 252 subjects(312 eyes) in The eye hospital, wenzhou medical university from March 7, 2020, to March 28, 2020. Sixty subjects(120 eyes) with normal IOP were divided into two groups. One group used an NCT without a baffle, another group used an NCT with a baffle. Another 192 subjects(192 eyes) were divided into four groups: Group A;(without a baffle+normal IOP), Group A;(without a baffle+high IOP), Group B;(with a baffle+normal IOP) and Group B;(with a baffle+high IOP). Particulate matter(PM) 2.5 and PM10 generated by all subjects were quantified during the NCT measurement. The IOP values were recorded simultaneously. Effects of baffle and IOP on aerosols generated during the NCT measurement were ***: In the normal eye group with a baffle, the aerosol density decreased in a wave-like shape near the NCT with the increase in the number of people measured for IOP, demonstrating no cumulative effect. However, in the normal eye group without a baffle, there was a cumulative effect. PM2.5 and PM10 in Group A;were higher than Group A;(both P<0.001). The PM2.5 and PM10 in Group B;were higher than Group B;(P<0.01, P<0.001 respectively). The PM10 of Group B;was lower than Group A;(P<0.01). PM2.5 in Group B;were lower than Group A;(P<0.01). The median of per capita PM2.5 and PM10 in the combined Group A;+A;were 0.80 and 1.10 μg/m;respectively, which were higher than 0.20 and 0.60 μg/m;in the combined Group B;+B;(both P<0.01). The median of per capita PM2.5 and PM10 in the combined Group A;+B;were 0.10 and 0.20 μg/m;respectively, which were lower than 1.30 and 1.70 μg/m;in the combined Group A;+B;(both P<0.001).CONCLUSION: More aerosols could be generated in patients with high IOP. Af

关键词： noncontact tonometry aerosol baffle intraocular pressure coronavirus disease 2019

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Revealing and predicting the long-term biomechanical response of orthokeratology by developing a patient-specific computational model

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 156-168页

作者： Yifeng Li Zhuoran Yang Ziming Yan Huibin Shi Zhanli Liu Kaijie Wang Department of Engineering Mechanics School of Aerospace Engineering Tsinghua University Beijing Tongren eye Center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology & Visual Sciences Key Lab

Orthokeratology(OK) is widely used for effective myopia correction and control. However, the incomplete understanding of its biomechanical mechanisms makes OK lens fitting rely heavily on clinician judgment, complicating accurate predictions of treatment outcomes. In this paper, we performed clinical experiments and numerical analysis to study corneal deformation modes and long-term changes in central corneal thickness. Clinical experiments were conducted on 194 Chinese myopic patients under OK treatment for 3 months. Based on the experimental data, a patient-specific computational biomechanical model for OK was established and validated. Specifically, the anisotropic mechanical properties of the cornea were incorporated into the model to describe the significant difference between its shear modulus(29.5 kPa) and tensile modulus(768.4 kPa). Additionally, a viscohyperelastic material model with a prolonged corneal relaxation time of 5.6 h was developed to capture the long-term deformation response. The results show that corneal thickness reduction in OK is primarily due to out-of-plane shear deformation,influenced by the cornea's low shear resistance. Modeling the extended corneal relaxation time is crucial for predicting long-term biomechanical responses. The computational model effectively captures long-term changes in central corneal thickness, potentially improving OK lens fitting accuracy.

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