Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological change...Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.展开更多
Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute cour...Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.展开更多
Kashin-Beck disease(KBD)is a regionally endemic chronic osteoarthropathy,while osteoarthritis(OA)is a degenerative joint disease characterized by progressive articular cartilage degradation and extracellular matrix re...Kashin-Beck disease(KBD)is a regionally endemic chronic osteoarthropathy,while osteoarthritis(OA)is a degenerative joint disease characterized by progressive articular cartilage degradation and extracellular matrix remodeling.Although KBD and OA share overlapping clinical and pathological features,key differences exist in their etiology and disease progression.KBD preferentially affects children aged 3-12 years,whereas OA predominantly affects older individuals between the age of 40-60 years.KBD cartilage necrosis originates in the deep layers of the epiphyseal plate and articular cartilage,progressing toward the cartilage surface.In contrast,OA cartilage destruction initiates at the articular cartilage surface and gradually progresses to expose the subchondral bone[1,2].展开更多
The retina,a crucial neural tissue,is responsible for transforming light signals into visual information,a process that necessitates a significant amount of energy.Mitochondria,the primary powerhouses of the cell,play...The retina,a crucial neural tissue,is responsible for transforming light signals into visual information,a process that necessitates a significant amount of energy.Mitochondria,the primary powerhouses of the cell,play an integral role in retinal physiology by fulfilling the high-energy requirements of photoreceptors and secondary neurons through oxidative phosphorylation.In a healthy state,mitochondria ensure proper visual function by facilitating efficient conversion and transduction of visual signals.However,in retinal degenerative diseases,mitochondrial dysfunction significantly contributes to disease progression,involving a decline in membrane potential,the occurrence of DNA mutations,increased oxidative stress,and imbalances in quality-control mechanisms.These abnormalities lead to an inadequate energy supply,the exacerbation of oxidative damage,and the activation of cell death pathways,ultimately resulting in neuronal injury and dysfunction in the retina.Mitochondrial transplantation has emerged as a promising strategy for addressing these challenges.This procedure aims to restore metabolic activity and function in compromised cells through the introduction of healthy mitochondria,thereby enhancing the cellular energy production capacity and offering new strategies for the treatment of retinal degenerative diseases.Although mitochondrial transplantation presents operational and safety challenges that require further investigation,it has demonstrated potential for reviving the vitality of retinal neurons.This review offers a comprehensive examination of the principles and techniques underlying mitochondrial transplantation and its prospects for application in retinal degenerative diseases,while also delving into the associated technical and safety challenges,thereby providing references and insights for future research and treatment.展开更多
Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological bi...Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.展开更多
An aging population is a double-edged sword.On one hand,advancements in biotechnology and healthcare allow more people to enjoy longer lives.On the other hand,increases in the aging population accompany a surge in age...An aging population is a double-edged sword.On one hand,advancements in biotechnology and healthcare allow more people to enjoy longer lives.On the other hand,increases in the aging population accompany a surge in age-associated diseases,particularly neurodegenerative disorders.Since aging is the primary risk factor for many neurodegenerative disorders,living longer does not necessarily equate to maintaining a reasonable quality of life(Feigin et al.,2020).展开更多
The immune system has been attracting increasing attention in the field of chronic neurological disorders in the central nervous system(CNS).Autoreactive T cells targeting CNS antigens play a crucial role in the devel...The immune system has been attracting increasing attention in the field of chronic neurological disorders in the central nervous system(CNS).Autoreactive T cells targeting CNS antigens play a crucial role in the development of various autoimmune diseases,such as multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Moreover,T cells are now recognized as a pivotal contributor to the pathology of neurodegenerative disorders,including Alzheimer's disease(AD),Parkinson's disease(PD),and multiple system atrophy.展开更多
Mitochondrial dysfunction and neurodegeneration:Progressive neurodegenerative diseases affect a significant proportion of the population;in a single year,there are as many as 276 million disabilities and 9 million dea...Mitochondrial dysfunction and neurodegeneration:Progressive neurodegenerative diseases affect a significant proportion of the population;in a single year,there are as many as 276 million disabilities and 9 million deaths as a result of neurological diseases.展开更多
Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations age.While tremendous progress has been made,our understanding of the mechanisms that ...Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations age.While tremendous progress has been made,our understanding of the mechanisms that underlie the development of these diseases remains far from com plete.More troubling,despite the growing emotional and financial toll being to ken by neurodegenerative disorders,existing treatment options are limited almost exclusively to those that help manage symptoms but that lack the ability to alter the progression of the disease(Liu et al.,2022).展开更多
Dear Editor,Neurodegenerative disorders (NDDs) are agerelated disorders characterized by the deposition of abnormal forms of proteins or the progressive loss of neurons in the brain.NDDs are classified according to th...Dear Editor,Neurodegenerative disorders (NDDs) are agerelated disorders characterized by the deposition of abnormal forms of proteins or the progressive loss of neurons in the brain.NDDs are classified according to their pathophysiological properties,including cognitive dysfunction,Alzheimer's disease (AD) and other dementias,Parkinson's disease,and motor neuron disease.The increased oxidative stress and neuro-inflammatory events contribute to neuronal atrophy and death in NDDs~([1]).Nitric oxide in the central nervous system has several functions,including the regulation of synaptic plasticity and neurosecretion.The physiological amount of nitric oxide is neuroprotective,whereas higher doses are noticeably neurotoxic~([2]).展开更多
Neurodegenerative diseases are often studied in isolation due to the vast differences in their underlying causes,the diversity in neuron types affected,and the variations in their clinical symptoms.However,there are c...Neurodegenerative diseases are often studied in isolation due to the vast differences in their underlying causes,the diversity in neuron types affected,and the variations in their clinical symptoms.However,there are common elements among these diseases,namely neuroinflammation,mitochondrial pathology,and an association with the gut-brain-immune axis that together suggest that these diseases a re more similar to each other than they first seem (Zhang et al.,2023).展开更多
Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging,which has been found to be a contributing factor for low back pain and might cause radiculopathy,myelopath...Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging,which has been found to be a contributing factor for low back pain and might cause radiculopathy,myelopathy,spinal stenosis,degenerative spondylolisthesis,and herniations.Its etiology is complex and multifactorial.Although genetics influence more dominant,the occupational and mechanical influences still persist as a major risk factor.This review emphasizes up-to-date knowledge regarding etiology of disc degeneration with special consideration on occupational,lifestyle factors,and genetic polymorphisms.展开更多
Neurodegenerative diseases are a group of neuronal disorders caused by progressive neuronal cell death in different regions of the human brain.Alzheimer's disease(AD)and Parkinson's disease(PD)are the most com...Neurodegenerative diseases are a group of neuronal disorders caused by progressive neuronal cell death in different regions of the human brain.Alzheimer's disease(AD)and Parkinson's disease(PD)are the most common types of neurodegenerative diseases that affect millions of people worldwide.There is no cure available for either disease.One of the pathological hallmarks of neurodegenerative diseases is the abnormal protein aggregation in the central nervous system.展开更多
The symptomatic degenerative meniscus continues to be a source of discomfort for a significant number of patients. With vascular penetration of less than onethird of the adult meniscus, healing potential in the settin...The symptomatic degenerative meniscus continues to be a source of discomfort for a significant number of patients. With vascular penetration of less than onethird of the adult meniscus, healing potential in the setting of chronic degeneration remains low. Continued hoop and shear stresses upon the degenerative meniscus results in gross failure, often in the form of complex tears in the posterior horn and midbody. Patient history and physical examination are critical to determine the true source of pain, particularly with the significant incidence of simultaneous articular pathology. Joint line tenderness, a positive Mc Murray test, and mechanical catching or locking can be highly suggestive of a meniscal source of knee pain and dysfunction. Radiographs and magnetic resonance imaging are frequently utilized to examine for osteoarthritis and to verify the presence of meniscal tears, in addition to ruling out other sources of pain. Non-operative therapy focused on nonsteroidal anti-inflammatory drugs and physical therapy may be able to provide pain relief as well as improve mechanical function of the knee joint. For patients re-fractory to conservative therapy, arthroscopic partial meniscectomy can provide short-term gains regarding pain relief, especially when combined with an effective, regular physiotherapy program. Patients with clear mechanical symptoms and meniscal pathology may benefit from arthroscopic partial meniscectomy, but surgery is not a guaranteed success, especially with concomitant articular pathology. Ultimately, the long-term outcomes of either treatment arm provide similar results for most patients. Further study is needed regarding the short and long-term outcomes regarding conservative and surgical therapy, with a particular focus on the economic impact of treatment as well.展开更多
Lumbar degenerative disc diseases cause low back pain(LBP). The maintenance of the height and stability of the intervertebral disc(IVD) space is an effective treatment for LBP. The following study evaluated the effect...Lumbar degenerative disc diseases cause low back pain(LBP). The maintenance of the height and stability of the intervertebral disc(IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration(IDD) in a preclinical setting. Compared with the IDD group, the fibroblast treatment group demonstrated effective maintenance of IVD height, reduced endplate degeneration, and improved nuclear magnetic resonance signals and overall histological structure. In doing so, fibrotic IVDs maintained the stability and biomechanics of the vertebra. This finding is in agreement with clinical findings that human nucleus pulposus(NP) fibrosis is essential for the maintenance of IVD height and mechanical properties in patients following percutaneous endoscopic lumbar discectomy(PELD). Mechanistically, we demonstrated that injected fibroblasts not only proliferated but also induced NP cells to adopt a fibrotic phenotype via the secretion of TGF-β.Finally, to better mimic human conditions, the efficacy of autologous fibroblast injection in the treatment of IDD was further examined in a nonhuman primate cynomolgus monkey model due to their capacity for upright posture. We showed that the injection of fibroblasts could maintain the IVD height and rescue IVD signals in cynomolgus monkeys. Taken together, the results of our study reveal that autologous fibroblast injection can enhance the natural process of fibrosis during acute and subacute stages of stress-induced IDD. Fibrotic IVDs can maintain the stability, biological activity, and mechanical properties of the intervertebral space, thus providing a new direction for the treatment of intervertebral space-derived lumbar degenerative diseases.展开更多
Lumbar degenerative disc disease(DDD)in the elderly population remains a global health problem,especially in patients with osteoporosis.Osteoporosis in the elderly can cause failure of internal fixation.Cortical bone ...Lumbar degenerative disc disease(DDD)in the elderly population remains a global health problem,especially in patients with osteoporosis.Osteoporosis in the elderly can cause failure of internal fixation.Cortical bone trajectory(CBT)is an effective,safe and minimally invasive technique for the treatment of lumbar DDD in patients with osteoporosis.In this review,we analyzed the anatomy,biomechanics,and advantages of the CBT technique in lumbar DDD and revision surgery.Additionally,the clinical trials and case reports,indications,advancements and limitations of this technique were further discussed and reviewed.Finally,we concluded that the CBT technique can be a practical,effective and safe alternative to traditional pedicle screw fixation,especially in DDD patients with osteoporosis.展开更多
Dynesys,a pedicle-based dynamic stabilization system,was introduced to overcome some undesirable complications of fusion procedures.Nevertheless,the theoretical advantages of Dynesys over fusion have not been clearly ...Dynesys,a pedicle-based dynamic stabilization system,was introduced to overcome some undesirable complications of fusion procedures.Nevertheless,the theoretical advantages of Dynesys over fusion have not been clearly confirmed.The purpose of this editorial was to compare clinical and radiological outcomes of patients who underwent Dynesys system with those who underwent posterior lumbar fusion according to the existing literature and to see if the application of the Dynesys system is superior to the traditional lumbar fusion surgery.According to published clinical reports,the short-term effects of the Dynesys dynamic stabilization system are similar to that of traditional lumbar fusion surgery.Three comparative studies of Dynesys dynamic stabilization and fusion surgery with medium-term follow-up are encouraging.However,the results from four single-treatment-arm and small-sample studies of case series with long-term follow-up were not encouraging.In the present circumstances,it is not possible to conclude that the Dynesys dynamic stabilization system is superior to fusion surgery for lumbar degenerative diseases.展开更多
Nerve growth factor(NGF) is a neurotrophic factor critical for cholinergic neuronal survival, phenotypic maintenance and plasticity in the mammalian brain. NGF has been implicated in the pathogenesis of neurodegenerat...Nerve growth factor(NGF) is a neurotrophic factor critical for cholinergic neuronal survival, phenotypic maintenance and plasticity in the mammalian brain. NGF has been implicated in the pathogenesis of neurodegenerative disorders, with direct administration of NGF into the brain capable of facilitating neuroprotection and repair.展开更多
Objective To investigate the prevalence and modifiable risk factors of degenerative valvular heart disease(DVHD)among elderly population in southern China.Methods A stratified multistage sampling method was used to re...Objective To investigate the prevalence and modifiable risk factors of degenerative valvular heart disease(DVHD)among elderly population in southern China.Methods A stratified multistage sampling method was used to recruit subjects.The contents of the survey included the questionnaire,laboratory examination,echocardiography,and other auxiliary examinations.The possible risk factors of DVHD were analyzed by logistic regression analysis.Results A total of 3538 subjects≥65 years of age were enrolled.One thousand three hundred and seven subjects(36.9%)were diagnosed with DVHD.Degenerative was the most common etiology of VHD.Prevalence of DVHD increased with advancing age.The prevalence of DVHD differed by living region(χ^(2)=45.594,P<0.001),educational level(χ^(2)=50.557,P<0.001),and occupation(χ^(2)=36.961,P<0.001).Risk factors associated with DVHD included age(two-fold increased risk for each 10-year increase in age),elevated level C-reactive protein(OR=1.346,95%CI:1.100-1.646),elevated level low density lipoprotein(OR=1.243,95%CI:1.064-1.451),coronary artery disease(OR=1.651,95%CI:1.085-2.513),smoking(OR=1.341,95%CI:1.132-1.589),and hypertension(OR=1.414,95%CI:1.221-1.638).Other significant risk factors included reduced or elevated level red blood cell(OR=1.347,95%CI:1.031-1.761;OR=1.599,95%CI:1.097-2.331;respectively),elevated level platelets(OR=1.891,95%CI:1.118-3.198),elevated level uric acid(OR=1.282,95%CI:1.112-1.479),and stroke(OR:1.738,95%CI=1.085-2.513).Conclusions The survey characterized the baseline conditions of DVHD cohort of elderly population in Guangzhou city.The established and emerging risk factors for DVHD may represent challenges and opportunities for therapy.展开更多
ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosi...ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosides,sugars,and xenobiotics.Interestingly,ABC transporters are highly expressed in the brain.While their functions in the brain still need to be elucidated,several members are implicated in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and frontotemporal dementia.In this perspective,we will review current knowledge of ABC transporters in the central nervous system in terms of physiological functions and pathology in neurodegeneration.Furthermore,we will explore the possibilities of ABC transporters as potential targets in the development of therapeutics for neurodegenerative diseases.展开更多
基金supported by the National Key Research and Development Program of China,No.2019YFA0111200the National Natural Science Foundation of China,Nos.U23A20436,82371047+3 种基金Key Research Project in Shanxi Province,No.202302130501008Shanxi Provincial Science Fund for Distinguished Young Scholars,No.202103021221008Key Research and Development Program in Shanxi Province,No.202204051001023Shanxi Medical University Doctor’s Startup Fund Project,No.SD22028(all to YG)。
文摘Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.
基金supported by the National Key Research and Development Program of China,No.2022YFC2703101(to YC)the National Natural Science Fundation of China,No.82371422(to YC)+1 种基金the National Innovation and Entrepreneurship Training Program for College Students,No.202310611408(to XW)the 1·3·5 Project for Disciplines of Excellence Clinical Research Fund,West China Hospital,Sichuan University,No.2023HXFH032(to YC)。
文摘Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.
基金supported by the 2023 training program for discipline leaders in natural science and engineering technology of Qinghai province-“Kunlun Talents·Science and Technology leaders.”。
文摘Kashin-Beck disease(KBD)is a regionally endemic chronic osteoarthropathy,while osteoarthritis(OA)is a degenerative joint disease characterized by progressive articular cartilage degradation and extracellular matrix remodeling.Although KBD and OA share overlapping clinical and pathological features,key differences exist in their etiology and disease progression.KBD preferentially affects children aged 3-12 years,whereas OA predominantly affects older individuals between the age of 40-60 years.KBD cartilage necrosis originates in the deep layers of the epiphyseal plate and articular cartilage,progressing toward the cartilage surface.In contrast,OA cartilage destruction initiates at the articular cartilage surface and gradually progresses to expose the subchondral bone[1,2].
基金supported by the National Natural Science Foundation of China,Nos.8247041526,81570864,82171053(to GYL)。
文摘The retina,a crucial neural tissue,is responsible for transforming light signals into visual information,a process that necessitates a significant amount of energy.Mitochondria,the primary powerhouses of the cell,play an integral role in retinal physiology by fulfilling the high-energy requirements of photoreceptors and secondary neurons through oxidative phosphorylation.In a healthy state,mitochondria ensure proper visual function by facilitating efficient conversion and transduction of visual signals.However,in retinal degenerative diseases,mitochondrial dysfunction significantly contributes to disease progression,involving a decline in membrane potential,the occurrence of DNA mutations,increased oxidative stress,and imbalances in quality-control mechanisms.These abnormalities lead to an inadequate energy supply,the exacerbation of oxidative damage,and the activation of cell death pathways,ultimately resulting in neuronal injury and dysfunction in the retina.Mitochondrial transplantation has emerged as a promising strategy for addressing these challenges.This procedure aims to restore metabolic activity and function in compromised cells through the introduction of healthy mitochondria,thereby enhancing the cellular energy production capacity and offering new strategies for the treatment of retinal degenerative diseases.Although mitochondrial transplantation presents operational and safety challenges that require further investigation,it has demonstrated potential for reviving the vitality of retinal neurons.This review offers a comprehensive examination of the principles and techniques underlying mitochondrial transplantation and its prospects for application in retinal degenerative diseases,while also delving into the associated technical and safety challenges,thereby providing references and insights for future research and treatment.
基金supported by Hunan Provincial Key Research and Development Program,No.2021SK2002(to BW)the Natural Science Foundation of Hunan Province of China(General Program),No.2021JJ30938(to YL)。
文摘Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
文摘An aging population is a double-edged sword.On one hand,advancements in biotechnology and healthcare allow more people to enjoy longer lives.On the other hand,increases in the aging population accompany a surge in age-associated diseases,particularly neurodegenerative disorders.Since aging is the primary risk factor for many neurodegenerative disorders,living longer does not necessarily equate to maintaining a reasonable quality of life(Feigin et al.,2020).
文摘The immune system has been attracting increasing attention in the field of chronic neurological disorders in the central nervous system(CNS).Autoreactive T cells targeting CNS antigens play a crucial role in the development of various autoimmune diseases,such as multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Moreover,T cells are now recognized as a pivotal contributor to the pathology of neurodegenerative disorders,including Alzheimer's disease(AD),Parkinson's disease(PD),and multiple system atrophy.
文摘Mitochondrial dysfunction and neurodegeneration:Progressive neurodegenerative diseases affect a significant proportion of the population;in a single year,there are as many as 276 million disabilities and 9 million deaths as a result of neurological diseases.
基金supported by a Canada Research Chair award to JP。
文摘Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations age.While tremendous progress has been made,our understanding of the mechanisms that underlie the development of these diseases remains far from com plete.More troubling,despite the growing emotional and financial toll being to ken by neurodegenerative disorders,existing treatment options are limited almost exclusively to those that help manage symptoms but that lack the ability to alter the progression of the disease(Liu et al.,2022).
文摘Dear Editor,Neurodegenerative disorders (NDDs) are agerelated disorders characterized by the deposition of abnormal forms of proteins or the progressive loss of neurons in the brain.NDDs are classified according to their pathophysiological properties,including cognitive dysfunction,Alzheimer's disease (AD) and other dementias,Parkinson's disease,and motor neuron disease.The increased oxidative stress and neuro-inflammatory events contribute to neuronal atrophy and death in NDDs~([1]).Nitric oxide in the central nervous system has several functions,including the regulation of synaptic plasticity and neurosecretion.The physiological amount of nitric oxide is neuroprotective,whereas higher doses are noticeably neurotoxic~([2]).
文摘Neurodegenerative diseases are often studied in isolation due to the vast differences in their underlying causes,the diversity in neuron types affected,and the variations in their clinical symptoms.However,there are common elements among these diseases,namely neuroinflammation,mitochondrial pathology,and an association with the gut-brain-immune axis that together suggest that these diseases a re more similar to each other than they first seem (Zhang et al.,2023).
文摘Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging,which has been found to be a contributing factor for low back pain and might cause radiculopathy,myelopathy,spinal stenosis,degenerative spondylolisthesis,and herniations.Its etiology is complex and multifactorial.Although genetics influence more dominant,the occupational and mechanical influences still persist as a major risk factor.This review emphasizes up-to-date knowledge regarding etiology of disc degeneration with special consideration on occupational,lifestyle factors,and genetic polymorphisms.
基金the NLRP3 inflammasome in the He laboratory was funded by NIH grant K22AI120988Wayne State University Startup
文摘Neurodegenerative diseases are a group of neuronal disorders caused by progressive neuronal cell death in different regions of the human brain.Alzheimer's disease(AD)and Parkinson's disease(PD)are the most common types of neurodegenerative diseases that affect millions of people worldwide.There is no cure available for either disease.One of the pathological hallmarks of neurodegenerative diseases is the abnormal protein aggregation in the central nervous system.
文摘The symptomatic degenerative meniscus continues to be a source of discomfort for a significant number of patients. With vascular penetration of less than onethird of the adult meniscus, healing potential in the setting of chronic degeneration remains low. Continued hoop and shear stresses upon the degenerative meniscus results in gross failure, often in the form of complex tears in the posterior horn and midbody. Patient history and physical examination are critical to determine the true source of pain, particularly with the significant incidence of simultaneous articular pathology. Joint line tenderness, a positive Mc Murray test, and mechanical catching or locking can be highly suggestive of a meniscal source of knee pain and dysfunction. Radiographs and magnetic resonance imaging are frequently utilized to examine for osteoarthritis and to verify the presence of meniscal tears, in addition to ruling out other sources of pain. Non-operative therapy focused on nonsteroidal anti-inflammatory drugs and physical therapy may be able to provide pain relief as well as improve mechanical function of the knee joint. For patients re-fractory to conservative therapy, arthroscopic partial meniscectomy can provide short-term gains regarding pain relief, especially when combined with an effective, regular physiotherapy program. Patients with clear mechanical symptoms and meniscal pathology may benefit from arthroscopic partial meniscectomy, but surgery is not a guaranteed success, especially with concomitant articular pathology. Ultimately, the long-term outcomes of either treatment arm provide similar results for most patients. Further study is needed regarding the short and long-term outcomes regarding conservative and surgical therapy, with a particular focus on the economic impact of treatment as well.
基金supported by the National Natural Science Foundation of China (81871790) & (81572167)the Shanghai Hospital Development Center Foundation (SHDC12016110)
文摘Lumbar degenerative disc diseases cause low back pain(LBP). The maintenance of the height and stability of the intervertebral disc(IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration(IDD) in a preclinical setting. Compared with the IDD group, the fibroblast treatment group demonstrated effective maintenance of IVD height, reduced endplate degeneration, and improved nuclear magnetic resonance signals and overall histological structure. In doing so, fibrotic IVDs maintained the stability and biomechanics of the vertebra. This finding is in agreement with clinical findings that human nucleus pulposus(NP) fibrosis is essential for the maintenance of IVD height and mechanical properties in patients following percutaneous endoscopic lumbar discectomy(PELD). Mechanistically, we demonstrated that injected fibroblasts not only proliferated but also induced NP cells to adopt a fibrotic phenotype via the secretion of TGF-β.Finally, to better mimic human conditions, the efficacy of autologous fibroblast injection in the treatment of IDD was further examined in a nonhuman primate cynomolgus monkey model due to their capacity for upright posture. We showed that the injection of fibroblasts could maintain the IVD height and rescue IVD signals in cynomolgus monkeys. Taken together, the results of our study reveal that autologous fibroblast injection can enhance the natural process of fibrosis during acute and subacute stages of stress-induced IDD. Fibrotic IVDs can maintain the stability, biological activity, and mechanical properties of the intervertebral space, thus providing a new direction for the treatment of intervertebral space-derived lumbar degenerative diseases.
基金Supported by National Natural Science Foundation of China,No.82202694。
文摘Lumbar degenerative disc disease(DDD)in the elderly population remains a global health problem,especially in patients with osteoporosis.Osteoporosis in the elderly can cause failure of internal fixation.Cortical bone trajectory(CBT)is an effective,safe and minimally invasive technique for the treatment of lumbar DDD in patients with osteoporosis.In this review,we analyzed the anatomy,biomechanics,and advantages of the CBT technique in lumbar DDD and revision surgery.Additionally,the clinical trials and case reports,indications,advancements and limitations of this technique were further discussed and reviewed.Finally,we concluded that the CBT technique can be a practical,effective and safe alternative to traditional pedicle screw fixation,especially in DDD patients with osteoporosis.
文摘Dynesys,a pedicle-based dynamic stabilization system,was introduced to overcome some undesirable complications of fusion procedures.Nevertheless,the theoretical advantages of Dynesys over fusion have not been clearly confirmed.The purpose of this editorial was to compare clinical and radiological outcomes of patients who underwent Dynesys system with those who underwent posterior lumbar fusion according to the existing literature and to see if the application of the Dynesys system is superior to the traditional lumbar fusion surgery.According to published clinical reports,the short-term effects of the Dynesys dynamic stabilization system are similar to that of traditional lumbar fusion surgery.Three comparative studies of Dynesys dynamic stabilization and fusion surgery with medium-term follow-up are encouraging.However,the results from four single-treatment-arm and small-sample studies of case series with long-term follow-up were not encouraging.In the present circumstances,it is not possible to conclude that the Dynesys dynamic stabilization system is superior to fusion surgery for lumbar degenerative diseases.
基金supported by the Canadian Institutes of Health Research(grant FRN 137064 to IA)the FDC Foundation+3 种基金the WB Family FoundationGerald and Carla Connor,the Weston Brain Institute(TR130117 to IA)a Frederick Banting and Charles Best Canada Graduate Scholarship(GSD 152271 to KX)in part,from funding through the Canada Research Chairs program(to IA)。
文摘Nerve growth factor(NGF) is a neurotrophic factor critical for cholinergic neuronal survival, phenotypic maintenance and plasticity in the mammalian brain. NGF has been implicated in the pathogenesis of neurodegenerative disorders, with direct administration of NGF into the brain capable of facilitating neuroprotection and repair.
基金supported by National Natural Science Foundation of China(No.81370295)Guangzhou Science and Technology Project(No.201508020261)。
文摘Objective To investigate the prevalence and modifiable risk factors of degenerative valvular heart disease(DVHD)among elderly population in southern China.Methods A stratified multistage sampling method was used to recruit subjects.The contents of the survey included the questionnaire,laboratory examination,echocardiography,and other auxiliary examinations.The possible risk factors of DVHD were analyzed by logistic regression analysis.Results A total of 3538 subjects≥65 years of age were enrolled.One thousand three hundred and seven subjects(36.9%)were diagnosed with DVHD.Degenerative was the most common etiology of VHD.Prevalence of DVHD increased with advancing age.The prevalence of DVHD differed by living region(χ^(2)=45.594,P<0.001),educational level(χ^(2)=50.557,P<0.001),and occupation(χ^(2)=36.961,P<0.001).Risk factors associated with DVHD included age(two-fold increased risk for each 10-year increase in age),elevated level C-reactive protein(OR=1.346,95%CI:1.100-1.646),elevated level low density lipoprotein(OR=1.243,95%CI:1.064-1.451),coronary artery disease(OR=1.651,95%CI:1.085-2.513),smoking(OR=1.341,95%CI:1.132-1.589),and hypertension(OR=1.414,95%CI:1.221-1.638).Other significant risk factors included reduced or elevated level red blood cell(OR=1.347,95%CI:1.031-1.761;OR=1.599,95%CI:1.097-2.331;respectively),elevated level platelets(OR=1.891,95%CI:1.118-3.198),elevated level uric acid(OR=1.282,95%CI:1.112-1.479),and stroke(OR:1.738,95%CI=1.085-2.513).Conclusions The survey characterized the baseline conditions of DVHD cohort of elderly population in Guangzhou city.The established and emerging risk factors for DVHD may represent challenges and opportunities for therapy.
文摘ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosides,sugars,and xenobiotics.Interestingly,ABC transporters are highly expressed in the brain.While their functions in the brain still need to be elucidated,several members are implicated in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and frontotemporal dementia.In this perspective,we will review current knowledge of ABC transporters in the central nervous system in terms of physiological functions and pathology in neurodegeneration.Furthermore,we will explore the possibilities of ABC transporters as potential targets in the development of therapeutics for neurodegenerative diseases.
