A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to ...A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.展开更多
Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recen...Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.展开更多
Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulp...Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell(NPC)death and IVDD,but the underlying mechanisms remain unclear.Although the effects of Drp1 phosphorylation in IVDD have been studied,it is currently unknown if small ubiquitin-like modifications(SUMOylation)of Drp1 regulate IVDD.This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase(MAPL),a mitochondrial SUMO E3 ligase,during IVDD progression.The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing.展开更多
Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-med...Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.展开更多
AIM:To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration(AMD)phenotypes.METHODS:A bidirectional Mendelian randomization(MR)analytical protocol was implemented,which utilized g...AIM:To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration(AMD)phenotypes.METHODS:A bidirectional Mendelian randomization(MR)analytical protocol was implemented,which utilized genome-wide association study(GWAS)summary statistics derived from the IEU OpenGWAS repositories.The investigation focused on 11 oxidative stress markers and AMD phenotypes,encompassing both wet and dry subtypes.The MR methodology incorporated inverse-variance weighted(IVW)calculations,MR-Egger statistical regression,weighted median approximation,and weighted mode assessments to estimate causative relationships.Sensitivity evaluations were conducted to verify result robustness and identify potential pleiotropy.RESULTS:Genetically predicted elevated catalase(CAT)concentrations demonstrated significant associations with heightened risks of overall AMD(IVW OR=1.084,95%CI:1.021-1.151,P=0.008)and wet AMD phenotype(IVW OR=1.113,95%CI:1.047-1.247,P=0.007).Higher genetically predicted albumin concentrations corresponded with reduced AMD risk(IVW OR=0.827,95%CI:0.715-0.957,P=0.013)but increased wet AMD risk(IVW OR=1.229,95%CI:1.036-1.458,P=0.018).Reverse MR analysis revealed that genetically predicted dry AMD exhibited significant association with reduced albumin levels(IVW OR=0.987,95%CI:0.979-0.996,P=0.004),while wet AMD corresponded with decreased total bilirubin(TBIL)and paraoxonase(PON)activity.CONCLUSION:The results offer strong support for a causal link between markers of oxidative stress and the development of AMD,indicating that oxidative processes play a role in driving the disease progression.展开更多
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are...Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such 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 diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,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 disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given 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 strategies.Currently,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 degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.展开更多
Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as ...Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.展开更多
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central ...Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.展开更多
Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extre...Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.展开更多
Frontotemporal lobar degeneration(FTLD)is a form of progressive dementia characterized by degeneration of the frontal and temporal lobes of the brain.This pathology involves a series of cognitive,behavioral,and neurol...Frontotemporal lobar degeneration(FTLD)is a form of progressive dementia characterized by degeneration of the frontal and temporal lobes of the brain.This pathology involves a series of cognitive,behavioral,and neurological symptoms that influence personality,decision-making ability,and language.展开更多
Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and in...Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and inflammatory cascade.While IDD naturally progresses with age,some factors such as mechanical trauma,lifestyle choices,and genetic abnormalities can elevate the risk of symptomatic disease progression.Current treatments,including pharmacological and surgical interventions,fail to halt disease progression or restore IDD function.Although biological therapies have been evaluated,their effectiveness in reversing long-term disc degeneration remains inconsistent.Mesenchymal stem cellbased therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations,ethical issues,etc.To date,mesenchymal stem cell-derived extracellular vesicles(EVs)have emerged as promising therapeutic agents for regeneration and anti-inflammation.Their therapeutic effects are attributed to several mechanisms,such as the induction of regenerative phenotype,apoptosis mitigation,and immunomodulation.In addition,the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration.Due to the problems in clinical use,however,the efficiency of the EVs should be overcome further by optimizing cell culture conditions,engineering them to deliver drugs and targeting molecules,etc.展开更多
Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and c...Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.展开更多
BACKGROUND Leiomyomas or fibroids commonly originate from the uterus;extrauterine leiomyomas are rare and most often arise from the broad ligament.Diagnosing broad ligament leiomyomas becomes particularly challenging ...BACKGROUND Leiomyomas or fibroids commonly originate from the uterus;extrauterine leiomyomas are rare and most often arise from the broad ligament.Diagnosing broad ligament leiomyomas becomes particularly challenging when they undergo degenerative changes because their clinical and radiological features often mimic those of ovarian tumors.We report a rare case of a giant broad ligament fibroid with cystic degeneration,which was initially mistaken for an ovarian mass.CASE SUMMARY A 49-year-old woman presented with mild abdominal distension and pain as the only symptoms.Upon abdominal examination,a large mass measuring approximately 30 cm and extending from the pelvic cavity to just below the xiphoid process was identified.Both transvaginal ultrasound and contrast-enhanced computed tomography suggested an ovarian origin of the mass.However,laparotomy confirmed that the mass originated from the right broad ligament.The mass was separated from the uterus and bilateral ovaries,with no involvement of the uterus or ovaries.The mass was completely resected with respecting the patient’s desire to retain her uterus and adnexa.Postoperative histopathological examination confirmed leiomyoma with cystic degeneration.CONCLUSION Broad ligament myomas mimic ovarian tumors;accurate diagnosis and careful operation are critical to avoid complications and ensure safety.展开更多
Neurodegenerative diseases account for a large and increasing health and economic burden worldwide.With an increasingly aged population,this burden is set to increase.Optic neuropathies make up a large proportion of n...Neurodegenerative diseases account for a large and increasing health and economic burden worldwide.With an increasingly aged population,this burden is set to increase.Optic neuropathies make up a large proportion of neurodegenerative diseases with glaucoma being highly prevalent.Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells and their axons which make up the optic nerve.It is the leading cause of irreversible vision loss and affects an estimated 80 million people.The mammalian central nervous system is non-regenerative and,once lost or injured,retinal ganglion cells cannot regenerate an axon into the optic nerve under basal conditions.Thus,strategies that provide neuroprotection to stressed,dysfunctional,or dying retinal ganglion cells are likely to be of high therapeutic and translational value.Advancing age,genetics,and elevated intraocular pressure are all major risk factors for glaucoma,however,all clinically available glaucoma treatments focus on intraocular pressure management and do not directly address the neurodegenerative component of glaucoma.展开更多
Proliferative diabetic retinopathy(PDR)affects approximately 6%of diabetic patients globally.The overall prevalence of diabetic retinopathy is around 22%.Wet age-related macular degeneration(ARMD),the sight-threatenin...Proliferative diabetic retinopathy(PDR)affects approximately 6%of diabetic patients globally.The overall prevalence of diabetic retinopathy is around 22%.Wet age-related macular degeneration(ARMD),the sight-threatening type of ARMD,affects approximately 1.2%-1.3%of the general population and represents 15%of total ARMD cases.While intravitreal anti-vascular endothelial growth factor injections are still the mainstay therapy,there are a few challenges,such as frequent administration,cost burden,and compliance barriers that prompt the need for exploration into systemic oral alternative drugs like fenofibrate,candesartan,and vorolanib.These oral therapies have the advantage of being noninvasive and systemically accessible with few logistical burdens.This review highlights current evidence supporting the use of oral therapies in PDR and wet ARMD management,along with practical limitations and future prospects.展开更多
AIM:To conduct a comprehensive bibliometric analysis of age-related macular degeneration(AMD)research from 2002 to 2022,identifying key contributing countries,institutions,authors,journals,and research hotspots to inf...AIM:To conduct a comprehensive bibliometric analysis of age-related macular degeneration(AMD)research from 2002 to 2022,identifying key contributing countries,institutions,authors,journals,and research hotspots to inform future research directions.METHODS:Publications related to AMD were retrieved from the Web of Science Core Collection(WoSCC)database for the period January 1,2002,to December 31,2022.The search was limited to English-language articles and reviews.Bibliometric analysis was performed using Microsoft Excel 2021 for data management and annual publication analysis.Visualization and network analyses were conducted using VOSviewer,CiteSpace,and the Bibliometrix package in R.Collaboration networks among countries,institutions,authors,and journals were mapped.Keywords were analyzed for co-occurrence to identify research hotspots.Metrics such as H-index,total link strength(TLS),and citation counts were used to assess impact.RESULTS:A total of 16715 publications were analyzed,showing a consistent increase in AMD research output over the past 20y,peaking at 1445 publications in 2021.The United States was the leading contributor with 31.8%of total publications,followed by China and the United Kingdom.The University of Melbourne emerged as the most productive institution with the highest TLS,indicating strong international collaborations.Professor Frank G.Holz was identified as the most influential author based on H-index and publication count.Investigative Ophthalmology&Visual Science was the most prolific journal and had the highest citation impact.Keyword co-occurrence analysis revealed four main research clusters:pathogenesis,therapy,epidemiology,and diagnosis.Emerging research hotspots included anti-vascular endothelial growth factor(VEGF)therapies,optical coherence tomography angiography,and artificial intelligence(AI)applications in diagnosis.CONCLUSION:The bibliometric analysis highlights significant growth and collaborative efforts in AMD research globally.Key contributors have advanced understanding in pathogenesis,therapeutic strategies,epidemiology,and diagnostic technologies.Future research should focus on interdisciplinary collaborations,novel therapeutic targets,personalized medicine,and technological innovations such as AI to effectively address the challenges posed by AMD.展开更多
AIM:To quantitatively assess central macular thickness(CMT),macular neovascularization(MNV)area,vascular tortuosity(VT),and vascular dispersion(VDisp)in neovascular age-related macular degeneration(nAMD),type 1 and ty...AIM:To quantitatively assess central macular thickness(CMT),macular neovascularization(MNV)area,vascular tortuosity(VT),and vascular dispersion(VDisp)in neovascular age-related macular degeneration(nAMD),type 1 and type 2 MNV,by means of optical coherence tomography(OCT)and OCT angiography(OCTA)techniques.METHODS:In this retrospective and observational case series,patients were classified into type 1 or type 2 MNV groups.A comprehensive panel of OCT and OCTA metrics was evaluated,including CMT,MNV area,VT,and VDisp.All subjects underwent a standardized intravitreal conbercept(IVC)regimen[3+pro re nata(PRN)]with a 12-month follow-up.MNV area was obtained by manual measurements with OCTA software,and VT and VDisp were calculated by automated analysis with Image J software.RESULTS:A total of 101 participants were included,with 51 patients in the type 1 MNV group(mean age 67.32±9.12y)and 50 patients in the type 2 MNV group(mean age 64.74±5.21y).The mean number of IVC injections was 3.98±1.53 for type 1 MNV and 3.73±0.81 for type 2 MNV.Both subtypes exhibited significant improvements in visual acuity,accompanied by marked reductions in CMT and MNV area(P<0.05)at 12mo after treatment.In type 2 MNV,VT significantly decreased(P<0.05),whereas no significant change was observed in VT for type 1 MNV.VDisp did not significantly changed in either sybtypes.Moreover,in type 1 MNV,final best-corrected visual acuity(BCVA)using logMAR correlated positively with both pre-and post-treatment CMT,while in type 2 MNV,a significant positive correlation was found between the number of injections and final CMT.CONCLUSION:This study shows that conbercept treatment significantly improves visual acuity and macular structure in both type 1 and type 2 MNV with reductions in CMT and MNV area.The significant reduction in VT in type 2 MNV suggests its potential as a biomarker for disease activity.The findings imply the quantitative assessment useful for the stratification,prognostication,and personalized management of MNV in nAMD.展开更多
In healthy intervertebral discs(IVDs),nerves and blood vessels are present only in the outer annulus fibrosus,while in degenerative IVDs,a large amount of nerve and blood vessel tissue grows inward.Evidence supports t...In healthy intervertebral discs(IVDs),nerves and blood vessels are present only in the outer annulus fibrosus,while in degenerative IVDs,a large amount of nerve and blood vessel tissue grows inward.Evidence supports that neurogenic inflammation produced by neuropeptides such as substance P and calcitonin gene related peptide released by the nociceptive nerve fibers innervating the IVDs plays a crucial role in the process of IVD degeneration.Recently,non-neuronal cells,including IVD cells and infiltrating immune cells,have emerged as important players in neurogenic inflammation.IVD cells and infiltrating immune cells express functional receptors for neuropeptides through which they receive signals from the nervous system.In return,IVD cells and immune cells produce neuropeptides and nerve growth factor,which stimulate nerve fibers.This communication generates a positive bidirectional feedback loop that can enhance the inflammatory response of the IVD.Recently emerging transient receptor potential channels have been recognized as contributors to neurogenic inflammation in the degenerative IVDs.These findings suggest that neurogenic inflammation involves complex pathophysiological interactions between sensory nerves and multiple cell types in the degenerative IVDs.Clarifying the mechanism of neurogenic inflammation in IVD degeneration may provide in-depth understanding of the pathology of discogenic low back pain.展开更多
Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture...Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture.These pathological changes result in disc height loss and functional decline,potentially leading to disc herniation.This comprehensive review aimed to address the current challenges in intervertebral disc degeneration treatment by evaluating the regenerative potential of stem cell-based therapies,with a particular focus on emerging technologies such as exosomes and gene vector systems.Through mechanisms such as differentiation,paracrine effects,and immunomodulation,stem cells facilitate extracellular matrix repair and reduce nucleus pulposus cell apoptosis.Despite recent advancements,clinical applications are hindered by challenges such as hypoxic disc environments and immune rejection.By analyzing recent preclinical and clinical findings,this review provided insights into optimizing stem cell therapy to overcome these obstacles and highlighted future directions in the field.展开更多
基金supported by the Army Laboratory Animal Foundation of China,No.SYDW[2020]22(to TC)the Shaanxi Provincial Key R&D Plan General Project of China,No.2022SF-236(to YM)the National Natural Science Foundation of China,No.82202070(to TC)。
文摘A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.
基金supported by the Michael Michelson Gift FundNIA grants R01AG073349 (M.V.R.), R01AG044034 (R.F.L.), and R01AG078609 (J.C.)
文摘Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.
基金supported by National Natural Science Foundation of China(82272549,82472505,and 82472498)National key Research and Development plan,Ministry of Science and Technology of the People’s Republic of China(2022YFC2407203)+2 种基金the Young Health Talents of Shanghai Municipal Health Commission,China(2022YQ011)China Medical Education Association(3030537245)The Youth Talent Project of Huashan Hospital(30302164006).
文摘Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell(NPC)death and IVDD,but the underlying mechanisms remain unclear.Although the effects of Drp1 phosphorylation in IVDD have been studied,it is currently unknown if small ubiquitin-like modifications(SUMOylation)of Drp1 regulate IVDD.This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase(MAPL),a mitochondrial SUMO E3 ligase,during IVDD progression.The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing.
基金supported by the National Natural Science Foundation of China (NSFC) (No.82172497)
文摘Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.
基金Supported by National Natural Science Foundation of China(No.82371033)Tianjin Health Bureau Fund(No.ZC20030)+4 种基金Tianjin Eye Hospital Fund Project(No.YKYB1911)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-016A)Nankai University Institute of Optometry Science Research Open Fund(No.YKPY2208)Tianjin Eye Hospital Science and Technology Fund(No.NKSGY202405)Xianyang Science and Technology Plan Project(No.L2022ZDYFSF038).
文摘AIM:To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration(AMD)phenotypes.METHODS:A bidirectional Mendelian randomization(MR)analytical protocol was implemented,which utilized genome-wide association study(GWAS)summary statistics derived from the IEU OpenGWAS repositories.The investigation focused on 11 oxidative stress markers and AMD phenotypes,encompassing both wet and dry subtypes.The MR methodology incorporated inverse-variance weighted(IVW)calculations,MR-Egger statistical regression,weighted median approximation,and weighted mode assessments to estimate causative relationships.Sensitivity evaluations were conducted to verify result robustness and identify potential pleiotropy.RESULTS:Genetically predicted elevated catalase(CAT)concentrations demonstrated significant associations with heightened risks of overall AMD(IVW OR=1.084,95%CI:1.021-1.151,P=0.008)and wet AMD phenotype(IVW OR=1.113,95%CI:1.047-1.247,P=0.007).Higher genetically predicted albumin concentrations corresponded with reduced AMD risk(IVW OR=0.827,95%CI:0.715-0.957,P=0.013)but increased wet AMD risk(IVW OR=1.229,95%CI:1.036-1.458,P=0.018).Reverse MR analysis revealed that genetically predicted dry AMD exhibited significant association with reduced albumin levels(IVW OR=0.987,95%CI:0.979-0.996,P=0.004),while wet AMD corresponded with decreased total bilirubin(TBIL)and paraoxonase(PON)activity.CONCLUSION:The results offer strong support for a causal link between markers of oxidative stress and the development of AMD,indicating that oxidative processes play a role in driving the disease progression.
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
基金supported by the National Natural Science Foundation of China,No.82171080Nanjing Medical Science and Technology Development Project,No.YKK23264Postgraduate Research&Practice Innovation Program of Jiangsu Province,Nos.JX10414151,JX10414152(all to KL)。
文摘Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such 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 diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,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 disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given 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 strategies.Currently,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 degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.
基金supported by the National Natural Science Foundation of China,Nos.81800919(to YX),82171140(to PW)the International Cooperation and Exchange of the National Natural Science Foundation of China,Nos.82020108008(to HS),81720108010(to SY).
文摘Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.
基金supported by grants from National Key R&D Program of China,No.2023YFC2506100(to JZ)the National Natural Science Foundation of China,No.82171062(to JZ).
文摘Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.
基金supported by the NIH grant(RO1 NS118066)the Blazer Foundation(to XJL)。
文摘Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.
基金funded by the project National Institute for Neurological Research(Programme EXCELES,ID Project No.LX22NPO5107)TEAMING:857560(EU)CZ.02.1.01/0.0/0.0/17_043/0009632(CZ)(to FA and JH)。
文摘Frontotemporal lobar degeneration(FTLD)is a form of progressive dementia characterized by degeneration of the frontal and temporal lobes of the brain.This pathology involves a series of cognitive,behavioral,and neurological symptoms that influence personality,decision-making ability,and language.
基金Supported by 2024 Yeungnam University Grant,No.224A480005.
文摘Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and inflammatory cascade.While IDD naturally progresses with age,some factors such as mechanical trauma,lifestyle choices,and genetic abnormalities can elevate the risk of symptomatic disease progression.Current treatments,including pharmacological and surgical interventions,fail to halt disease progression or restore IDD function.Although biological therapies have been evaluated,their effectiveness in reversing long-term disc degeneration remains inconsistent.Mesenchymal stem cellbased therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations,ethical issues,etc.To date,mesenchymal stem cell-derived extracellular vesicles(EVs)have emerged as promising therapeutic agents for regeneration and anti-inflammation.Their therapeutic effects are attributed to several mechanisms,such as the induction of regenerative phenotype,apoptosis mitigation,and immunomodulation.In addition,the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration.Due to the problems in clinical use,however,the efficiency of the EVs should be overcome further by optimizing cell culture conditions,engineering them to deliver drugs and targeting molecules,etc.
基金funded by Chinese NSFC(Grant Nos.:82373336,82303238,and U22A20311,Sichuan Science and Technology Department,China(GrantNos.:2024NSFSC1945,,and 2023NSFSC0667)the Third People's Hospital of Chengdu Clinical Research Program,China(Grant Nos.:CSY-YN-01-2023-013,CSYYN-01-2023-005,and CSY-YN-03-2024-003)+1 种基金Sichuan University“From O to 1”Innovative Research Project,China(Project No.:2023SCUH0024)Health Commission of Chengdu,China(Grant No.:2024291).
文摘Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.
文摘BACKGROUND Leiomyomas or fibroids commonly originate from the uterus;extrauterine leiomyomas are rare and most often arise from the broad ligament.Diagnosing broad ligament leiomyomas becomes particularly challenging when they undergo degenerative changes because their clinical and radiological features often mimic those of ovarian tumors.We report a rare case of a giant broad ligament fibroid with cystic degeneration,which was initially mistaken for an ovarian mass.CASE SUMMARY A 49-year-old woman presented with mild abdominal distension and pain as the only symptoms.Upon abdominal examination,a large mass measuring approximately 30 cm and extending from the pelvic cavity to just below the xiphoid process was identified.Both transvaginal ultrasound and contrast-enhanced computed tomography suggested an ovarian origin of the mass.However,laparotomy confirmed that the mass originated from the right broad ligament.The mass was separated from the uterus and bilateral ovaries,with no involvement of the uterus or ovaries.The mass was completely resected with respecting the patient’s desire to retain her uterus and adnexa.Postoperative histopathological examination confirmed leiomyoma with cystic degeneration.CONCLUSION Broad ligament myomas mimic ovarian tumors;accurate diagnosis and careful operation are critical to avoid complications and ensure safety.
基金supported by St.Erik Eye Hospital philanthropic donations,Vetenskapsrådet 2022-00799(to PAW).
文摘Neurodegenerative diseases account for a large and increasing health and economic burden worldwide.With an increasingly aged population,this burden is set to increase.Optic neuropathies make up a large proportion of neurodegenerative diseases with glaucoma being highly prevalent.Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells and their axons which make up the optic nerve.It is the leading cause of irreversible vision loss and affects an estimated 80 million people.The mammalian central nervous system is non-regenerative and,once lost or injured,retinal ganglion cells cannot regenerate an axon into the optic nerve under basal conditions.Thus,strategies that provide neuroprotection to stressed,dysfunctional,or dying retinal ganglion cells are likely to be of high therapeutic and translational value.Advancing age,genetics,and elevated intraocular pressure are all major risk factors for glaucoma,however,all clinically available glaucoma treatments focus on intraocular pressure management and do not directly address the neurodegenerative component of glaucoma.
文摘Proliferative diabetic retinopathy(PDR)affects approximately 6%of diabetic patients globally.The overall prevalence of diabetic retinopathy is around 22%.Wet age-related macular degeneration(ARMD),the sight-threatening type of ARMD,affects approximately 1.2%-1.3%of the general population and represents 15%of total ARMD cases.While intravitreal anti-vascular endothelial growth factor injections are still the mainstay therapy,there are a few challenges,such as frequent administration,cost burden,and compliance barriers that prompt the need for exploration into systemic oral alternative drugs like fenofibrate,candesartan,and vorolanib.These oral therapies have the advantage of being noninvasive and systemically accessible with few logistical burdens.This review highlights current evidence supporting the use of oral therapies in PDR and wet ARMD management,along with practical limitations and future prospects.
基金Supported by the National Natural Science Foundation of China(No.82371033)the Tianjin Natural Science Foundation(No.21JCZDJC01250)the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-016A).
文摘AIM:To conduct a comprehensive bibliometric analysis of age-related macular degeneration(AMD)research from 2002 to 2022,identifying key contributing countries,institutions,authors,journals,and research hotspots to inform future research directions.METHODS:Publications related to AMD were retrieved from the Web of Science Core Collection(WoSCC)database for the period January 1,2002,to December 31,2022.The search was limited to English-language articles and reviews.Bibliometric analysis was performed using Microsoft Excel 2021 for data management and annual publication analysis.Visualization and network analyses were conducted using VOSviewer,CiteSpace,and the Bibliometrix package in R.Collaboration networks among countries,institutions,authors,and journals were mapped.Keywords were analyzed for co-occurrence to identify research hotspots.Metrics such as H-index,total link strength(TLS),and citation counts were used to assess impact.RESULTS:A total of 16715 publications were analyzed,showing a consistent increase in AMD research output over the past 20y,peaking at 1445 publications in 2021.The United States was the leading contributor with 31.8%of total publications,followed by China and the United Kingdom.The University of Melbourne emerged as the most productive institution with the highest TLS,indicating strong international collaborations.Professor Frank G.Holz was identified as the most influential author based on H-index and publication count.Investigative Ophthalmology&Visual Science was the most prolific journal and had the highest citation impact.Keyword co-occurrence analysis revealed four main research clusters:pathogenesis,therapy,epidemiology,and diagnosis.Emerging research hotspots included anti-vascular endothelial growth factor(VEGF)therapies,optical coherence tomography angiography,and artificial intelligence(AI)applications in diagnosis.CONCLUSION:The bibliometric analysis highlights significant growth and collaborative efforts in AMD research globally.Key contributors have advanced understanding in pathogenesis,therapeutic strategies,epidemiology,and diagnostic technologies.Future research should focus on interdisciplinary collaborations,novel therapeutic targets,personalized medicine,and technological innovations such as AI to effectively address the challenges posed by AMD.
基金Supported by Natural Science Foundation of Shandong Province(No.ZR2023MH363)Bethune Langmu Young Scholars Research Fund Project(No.BJ-LM2021007J).
文摘AIM:To quantitatively assess central macular thickness(CMT),macular neovascularization(MNV)area,vascular tortuosity(VT),and vascular dispersion(VDisp)in neovascular age-related macular degeneration(nAMD),type 1 and type 2 MNV,by means of optical coherence tomography(OCT)and OCT angiography(OCTA)techniques.METHODS:In this retrospective and observational case series,patients were classified into type 1 or type 2 MNV groups.A comprehensive panel of OCT and OCTA metrics was evaluated,including CMT,MNV area,VT,and VDisp.All subjects underwent a standardized intravitreal conbercept(IVC)regimen[3+pro re nata(PRN)]with a 12-month follow-up.MNV area was obtained by manual measurements with OCTA software,and VT and VDisp were calculated by automated analysis with Image J software.RESULTS:A total of 101 participants were included,with 51 patients in the type 1 MNV group(mean age 67.32±9.12y)and 50 patients in the type 2 MNV group(mean age 64.74±5.21y).The mean number of IVC injections was 3.98±1.53 for type 1 MNV and 3.73±0.81 for type 2 MNV.Both subtypes exhibited significant improvements in visual acuity,accompanied by marked reductions in CMT and MNV area(P<0.05)at 12mo after treatment.In type 2 MNV,VT significantly decreased(P<0.05),whereas no significant change was observed in VT for type 1 MNV.VDisp did not significantly changed in either sybtypes.Moreover,in type 1 MNV,final best-corrected visual acuity(BCVA)using logMAR correlated positively with both pre-and post-treatment CMT,while in type 2 MNV,a significant positive correlation was found between the number of injections and final CMT.CONCLUSION:This study shows that conbercept treatment significantly improves visual acuity and macular structure in both type 1 and type 2 MNV with reductions in CMT and MNV area.The significant reduction in VT in type 2 MNV suggests its potential as a biomarker for disease activity.The findings imply the quantitative assessment useful for the stratification,prognostication,and personalized management of MNV in nAMD.
文摘In healthy intervertebral discs(IVDs),nerves and blood vessels are present only in the outer annulus fibrosus,while in degenerative IVDs,a large amount of nerve and blood vessel tissue grows inward.Evidence supports that neurogenic inflammation produced by neuropeptides such as substance P and calcitonin gene related peptide released by the nociceptive nerve fibers innervating the IVDs plays a crucial role in the process of IVD degeneration.Recently,non-neuronal cells,including IVD cells and infiltrating immune cells,have emerged as important players in neurogenic inflammation.IVD cells and infiltrating immune cells express functional receptors for neuropeptides through which they receive signals from the nervous system.In return,IVD cells and immune cells produce neuropeptides and nerve growth factor,which stimulate nerve fibers.This communication generates a positive bidirectional feedback loop that can enhance the inflammatory response of the IVD.Recently emerging transient receptor potential channels have been recognized as contributors to neurogenic inflammation in the degenerative IVDs.These findings suggest that neurogenic inflammation involves complex pathophysiological interactions between sensory nerves and multiple cell types in the degenerative IVDs.Clarifying the mechanism of neurogenic inflammation in IVD degeneration may provide in-depth understanding of the pathology of discogenic low back pain.
基金Supported by Henan Province Key Research and Development Program,No.231111311000Henan Provincial Science and Technology Research Project,No.232102310411+2 种基金Henan Province Medical Science and Technology Key Project,No.LHGJ20220566 and No.LHGJ20240365Henan Province Medical Education Research Project,No.WJLX2023079Zhengzhou Medical and Health Technology Innovation Guidance Program,No.2024YLZDJH022.
文摘Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture.These pathological changes result in disc height loss and functional decline,potentially leading to disc herniation.This comprehensive review aimed to address the current challenges in intervertebral disc degeneration treatment by evaluating the regenerative potential of stem cell-based therapies,with a particular focus on emerging technologies such as exosomes and gene vector systems.Through mechanisms such as differentiation,paracrine effects,and immunomodulation,stem cells facilitate extracellular matrix repair and reduce nucleus pulposus cell apoptosis.Despite recent advancements,clinical applications are hindered by challenges such as hypoxic disc environments and immune rejection.By analyzing recent preclinical and clinical findings,this review provided insights into optimizing stem cell therapy to overcome these obstacles and highlighted future directions in the field.
