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Monogenic gene therapy for glaucoma and optic nerve injury

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Neural Regeneration Research 2025年第3期20卷 815-816页

作者： Chikako Harada Xiaoli guo Takayuki Harada Visual Research Project Tokyo Metropolitan Institute of Medical ScienceTokyoJapan

The prevalence of glaucoma, the second leading cause of global blindness, is increasing due to aging populations. In glaucoma, degeneration of the optic nerve and retinal ganglion cells(RGCs) causes visual field defec... 详细信息

关键词： visual glaucoma degeneration

Asking one mechanism in glial cells during neuroinflammation

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Neural Regeneration Research 2025年第4期20卷 1077-1078页

作者： Xiaoli guo Chikako Harada Takayuki Harada Visual Research Project Tokyo Metropolitan Institute of Medical ScienceTokyoJapan

Multiple sclerosis(MS),which is characterized by inflammatory demyelination in the central nervous system(CNS),is the most common neurological disease in the young adult *** autoimmune encephalomyelitis(EAE),an animal model of MS,is often used in preclinical *** data indicate that in addition to immune cells such as T cells and dendritic cells,CNS resident microglia and astrocytes play important roles in demyelinating neuroinflammation(Healy et al.,2022).In particular,microglia are key immune-competent cells that can respond to environmental *** depletion of transforming growth factor-β-activated kinase 1,a mitogen-associated protein kinase kinase kinase,in microglia is reported to reduce CNS inflammation and diminish axonal and myelin damage *** suggests that elucidating the mechanisms of microglia-specific responses during pathologies may help in the development of treatments that reduce EAE/MS disease severity(Goldmann et al.,2013).

关键词： inflammation clinical

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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Neural Regeneration Research 2025年第9期20卷 2513-2519页

作者： desmond A.Nunez Ru C.guo division of Otolaryngology–Head&Neck Surgery Department of SurgeryFaculty of MedicineThe University of British ColumbiaVancouverBCCanada division of Otolaryngology–Head&Neck Surgery Gordon&Leslie Diamond Health Care CentreVancouver General HospitalVancouverBCCanada Faculty of Medicine–The University of British Columbia VancouverBCCanada

Hearing loss is the third leading cause of human ***-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health ***-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing *** etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental *** stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing *** non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic *** hair cell death is a central histopathological finding in sensorineural hearing *** these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing *** EMBASE,Ovid MEdLINE,Web of Science Core Collection,and *** databases over the period August 1,2018 to july 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical *** red clinical trials known to the senior author we re also assessed.A total of 222studies were thus *** excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text *** resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative *** miR-34a and miR-29b levels increase with age in *** miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT

关键词： hearing loss hypoxia microRNAs oxidative stress sensorineural

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi james d.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long jiajia Liu Yu Wang Haidong guo guohong Cui department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina School of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

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Neural Regeneration Research 2025年第5期20卷 1416-1430页

作者： Mou Gao Qin dong dan Zou Zhijun Yang Lili guo Ruxiang Xu department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina department of Neurosurgery Chinese PLA General HospitalBeijingChina department of Neurology Fu Xing HospitalCapital Medical UniversityBeijingChina

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and *** previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological ***,the mechanism of CXCR4 upregulation in induced neural stem cells remains *** this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 ***,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial *** agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury ***,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head *** conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neura

关键词： Akt signaling cerebral edema closed head injury Crry CXCR4 induced neural stem cell microglia neuroinflammation

Effects of the extrusion parameters on microstructure,texture and room temperature mechanical properties of extruded Mg-2.49Nd-1.82Gd-0.2Zn-0.2Zr alloy

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International journal of Minerals,Metallurgy and Materials 2025年第1期32卷 136-146页

作者： Chenjin Zhang Guangyu Yang Lei Xiao Zhiyong Kan jing guo Qiang Li Wanqi jie State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an 710072China College of Materials Science and Engineering Fuzhou UniversityFuzhou 350108China College of Chemistry and Environmental Science Qujing Normal UniversityQujing 655011China

Microstructure,texture,and mechanical properties of the extruded Mg-2.49Nd-1.82Gd-0.2Zn-0.2Zr alloy were investigated at different extrusion temperatures(260 and 320℃),extrusion ratios(10:1,15:1,and 30:1),and extrusion speeds(3 and 6 mm/s).The experimental results exhibited that the grain sizes after extrusion were much finer than that of the homogenized alloy,and the second phase showed streamline distribution along the extrusion direction(Ed).With extrusion temperature increased from 260 to 320℃,the microstructure,texture,and mechanical properties of alloys changed *** dynamic recrystallization(dRX)degree and grain sizes enhanced as the extrusion ratio increased from 10:1 to 30:1,and the strength gradually decreased but elongation(EL)*** the extrusion speed increased from 3 to 6 mm/s,the grain sizes and dRX degree increased significantly,and the samples presented the typical-rare-earth(RE)*** alloy extruded at 260℃ with extrusion ratio of 10:1 and extrusion speed of 3 mm/s showed the tensile yield strength(TYS)of 213 MPa and EL of 30.6%.After quantitatively analyzing the contribution of strengthening mechanisms,it was found that the grain boundary strengthening and dislocation strengthening played major roles among strengthening *** results provide some guidelines for enlarging the industrial application of extruded Mg-RE alloy.

关键词： Mg-rare earth alloys extrusion temperature extrusion ratio extrusion speed strengthening mechanisms

Clinical effects of phospholipase d2 in attenuating acute pancreatitis

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World journal of Gastroenterology 2025年第2期31卷 52-60页

作者： jin-Wei Niu guo-Chao Zhang Wu Ning Hai-Bin Liu Hua Yang Chao-Feng Li department of General Surgery China-Japan Friendship HospitalBeijing 100029China

BACKGROUNd The objective of the current study was to elucidate the clinical mechanism through which phospholipase d2(PLd2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute *** To elucidate the clinical mechanism through which PLd2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute *** The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)*** data was collected for each *** blot analysis assessed PLd2 protein expression in patient ***-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil *** levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent *** migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLd2 on neutrophil *** Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLd2 protein in the severe group was lower than that in the moderate and mild groups(Pd2 in the moderate group was also lower than that in the mild group(Pd with PLd2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(Pd the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumo

关键词： Phospholipase d2 Neutrophil migration Acute pancreatitis Retrospective analysis Inflammatory response

Impacts of climate gradients on the vegetation phenology of major land use types in Central Asia （1981-2008）

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Frontiers of Earth Science 2012年第2期6卷 206-225页

作者： jahan KARIYEVA Willem j.d. van LEEUWEN Connie A. WOOdHOUSE School of Geography and development The University of Arizona Tucson AZ 85721 USA School of Natural Resources and the Environment - Office of Arid Lands Studies - Arizona Remote Sensing Center The University of Arizona Tucson AZ 85721 USA

Time-series of land surface phenology （LSP） data offer insights about vegetation growth patterns. They can be generated by exploiting the temporal and spectral reflectance properties of land surface components. Inter- annual and seasonal LSP data are important for under- standing and predicting an ecosystem＇s response to variations caused by natural and anthropogenic drivers. This research examines spatio-temporal change patterns and interactions between terrestrial phenology and 28 years of climate dynamics in Central Asia. Long-term （1981-2008） LSP records such as timing of the start, peak and length of the growing season and vegetation productivity were derived from remotely sensed vegetation greenness data. The patterns were analyzed to identify and characterize the impact of climate drivers at regional scales. We explored the relationships between phenologi- cal and precipitation and temperature variables for three generalized land use types that were exposed to decade- long regional drought events and intensified land and water resource use： rainfed agriculture, irrigated agriculture, and non-agriculture. To determine whether and how LSP dynamics are associated with climate patterns, a series of simple linear regression analyses between these two variables was executed. The three land use classes showed unique phenological responses to climate variation across Central Asia. Most of the phenological response variables were shown to be positively correlated to precipitation and negatively correlated to temperature. The most substantial climate variable affecting phenological responses of all three land use classes was a spring temperature regime. These results indicate that future higher temperatures would cause earlier and longer growing seasons.

关键词： phenology land use climate variability