The purpose of this study was to investigate the intensity-specific regenerative effects of microcurrent therapy on gastrocnemius muscle atrophy induced by cast-immobilization in rabbits. Fifteen rabbits were randomly...The purpose of this study was to investigate the intensity-specific regenerative effects of microcurrent therapy on gastrocnemius muscle atrophy induced by cast-immobilization in rabbits. Fifteen rabbits were randomly allocated to 3 groups after cast removal: cast-immobilization and sham microcurrent therapy for 2 weeks(group 1); castimmobilization and microcurrent therapy(25 μA) for 2 weeks(group 2); cast-immobilization and microcurrent therapy(5,000 μA) for 2 weeks(group 3). Clinical parameters [calf circumference, compound muscle action potential(CMAP) of the tibial nerve, thickness of gastrocnemius muscle], cross sectional area of gastrocnemius muscle fibres,and immunohistochemistry was evaluated. The clinical parameters representing mean atrophic changes in group 2 were significantly lower than those in group 3. The cross sectional area of the gastrocnemius muscle fibres and immunohistochemical parameters in group 2 were significantly greater than those in group 3. The results showed that low-intensity microcurrent therapy can more effectively promote regeneration in atrophied gastrocnemius muscle than high-intensity microcurrent therapy.展开更多
Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be el...Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.展开更多
Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in thi...Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in this process.Methods: 8-week-old male C57BL/6J mice were carried out combined exercise for 10 weeks. One week before the end of the intervention, mice underwent cast immobilization. Additionally, to investigate the potential mechanism in exercise-induced protection of skeletal muscle, mice in the exercise preconditioning group were administered TC-E-5003(an inhibitor of Prmt1 enzymatic activity). Exercise performance, muscle mass, and the cross-sectional area(CSA) of muscle fibers were analyzed. Besides, Prmt1 and Sestrin1(Sesn1) were either overexpressed or inhibited in C2C12 myotubes to elucidate the underlying mechanism.Results: Exercise preconditioning not only significantly improved muscle mass and motor ability in immobilized mice but also inhibited excessive activation of degradation pathways and enhanced protein synthesis. Importantly, Prmt1 mediated the protective effects of exercise preconditioning on muscle atrophy. Mechanistically,Prmt1 regulated the p38 mitogen-activated protein kinase(p38)/activating transcription factor 2(ATF2)pathway, which modulates Sesn1 expression. Sesn1 acts as a downstream of Prmt1 and ATF2, contributing to the myoblast differentiation and skeletal muscle regeneration through AMP-Activated protein kinase α2(AMPKα2)/transcriptional co-activator PPAR-γ co-activator-1 α(PGC-1α) signaling pathway.Conclusions: Taken together, our results highlighted the effectiveness of exercise preconditioning in preventing muscle atrophy via the Prmt1-Sesn1 pathway.展开更多
Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated ...Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.展开更多
Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as ...Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.展开更多
Objectives:Restore muscular trophism and voluntary contractile capacity through cell therapy in atrophied muscles in SCI patients.Setting:Out Patient Treatment,Universidad Maimonides,Buenos Aires,Argentina.Methods:Aft...Objectives:Restore muscular trophism and voluntary contractile capacity through cell therapy in atrophied muscles in SCI patients.Setting:Out Patient Treatment,Universidad Maimonides,Buenos Aires,Argentina.Methods:After receiving spinal cord cell therapy and intensive rehabilitation,7 chronic complete spinal cord injury(SCI)patients(4 people with paraplegia and 3 people with quadriplegia)regained muscular electrical activity in previously denervated territories.However,signs of severe muscular atrophy persisted.Looking to reverse chronic muscular atrophy,atrophied muscles with electrical activity were implanted with autologous type 1 macrophages(Mo1)and autologous tissue-specific T helper 1 Cells(Th1)associated with autologous muscular progenitor cells(MPC).The Mo1 and Th1 used cells were named Effector Cells(EC).Each muscle received between 6 to 8 implants,one every 6 weeks.Cellular therapy was combined with intensive rehabilitation program.Results:Sonogram and histological signs of recovery started eight weeks after the first implant.Sonograms showed progressively muscle volume increasing and gradually replacement of hyperechogenic muscle tissue by hypoechogenic muscle bands(resembling normalmuscular structure).New bands were distributed parallel to the main muscle axis,along the entire muscular length.Histological samples of hypoechogenic bands showed new and normal muscular tissue.Changes were seen in 7/7 patients.Non-significant side events were detected in any patient over the 24 months of follow up.Conclusions:The results presented here suggest that the combination of immune and regenerative cell therapy may play an important therapeutic role in clinical and histological recovery of chronic muscular atrophy.展开更多
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomar...Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.展开更多
Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and atrophy.The genetic cause of SMA was understood in 1995 when loss or impairment...Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and atrophy.The genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene therapies.SMA was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between individuals.Now,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice versa.Additionally,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.展开更多
Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r...Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.展开更多
BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resol...BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO_(2) laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.展开更多
Segmental atrophy(SA)of the liver is a rare,often underrecognized,benign condition that presents as a mass lesion,mimicking a neoplasm,which poses a significant diagnostic challenge.Given its rarity,only a limited num...Segmental atrophy(SA)of the liver is a rare,often underrecognized,benign condition that presents as a mass lesion,mimicking a neoplasm,which poses a significant diagnostic challenge.Given its rarity,only a limited number of case reports and series have been published,resulting in sparse literature on the entity.This review aims to summarize the clinicopathologic and diagnostic features of SA and thus improve its recognition.展开更多
Background : Cancer-associated cardiac cachexia(CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods : This study established CAC...Background : Cancer-associated cardiac cachexia(CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods : This study established CACC models in C57BL/6J and BALB/c mice using orthotopic, intra-abdominal, and hematogenous metastatic tumor induction. Multimodal cardiac assessments, including echocardiography, transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis, and ex vivo cardiomyocyte contractility assays, were systematically applied. Results : Metastatic burden triggered CACC characterized by cardiac mass reduction, epicardial fat depletion, interstitial fibrosis, and electrocardiographic abnormalities. Histopathological analysis revealed cardiomyocyte atrophy, myofibrillar disarray, mitochondrial dysfunction, and ubiquitin-mediated Myh6 degradation via Mu RF-1, accompanied by compensatory Myh7 upregulation. These findings mechanistically link tumor-induced cachexia to cardiac dysfunction through contractile protein remodeling. Conclusion : This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer-related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration.展开更多
Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still u...Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still unclear.In this study,the male C57BL/6J mice were fed a high-fat diet(HFD)for 12 weeks to induce obesity,and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks.The results showed that KO treatment reduced body weight,fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice.Importantly,KO treatment attenuated skeletal muscle atrophy in HFD-fed mice,as evidenced by preserving skeletal muscle mass,average myofiber cross-sectional area and grip strength.KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle.Additionally,KO treatment inhibited the transcriptional activities of nuclear factor-κB(NF-κB)p65 and forkhead box O 3a(FoxO3a),and then down-regulated muscle atrophy F-box(MAFbx)and muscle-specific RING finger protein 1(MuRF1)protein levels in skeletal muscle from HFD-fed mice.KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway.Furthermore,KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1αpathway.Collectively,KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.展开更多
BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increas...BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increase re-tear rates.AIM To investigate the potential inhibitory effects of alpha-tocopherol(vitamin E)and OTR-4131 on muscle atrophy,fatty infiltration,and fibrosis in rotator cuff muscles following a massive RCT using a Wistar rat model,and establish a standardized methodology for evaluating potential therapeutic agents.METHODS This protocol outlines a controlled animal study using 40 male Wistar rats,randomized into five groups.The experimental groups will receive either systemic administration of alpha-tocopherol or local administration of OTR-4131 via intramuscular injection into the supraspinatus and infraspinatus muscles.Two sham groups will receive systemic and local saline injections respectively,while a control group will undergo no intervention.The interventions will be administered after surgical transection of the supraspinatus and infraspinatus tendons.Outcomes will be assessed via wet muscle weight measurements,muscle fiber diameter,fatty infiltration percentage,and fibrosis evaluation using histological methods.RESULTS The study anticipates that alpha-tocopherol and OTR-4131 will reduce muscle atrophy,fatty infiltration,and fibrosis compared to control and sham groups,supporting their potential protective role in rotator cuff muscle degeneration.CONCLUSION The results are expected to improve the understanding on the role of alpha-tocopherol and OTR-4131 in rotator cuff muscle protection after massive RCT and may serve as a foundation for further preclinical and clinical research aimed at improving rotator cuff repair outcomes.展开更多
Testicular torsion is a urological emergency that requires prompt diagnosis and treatment,accounting for 10%-15%of cases of acute scrotum.[1]It occurs most frequently during the perinatal period and adolescence and ca...Testicular torsion is a urological emergency that requires prompt diagnosis and treatment,accounting for 10%-15%of cases of acute scrotum.[1]It occurs most frequently during the perinatal period and adolescence and can occur at any age.[2]The incidence of testicular torsion is 1/4,000 in males under 25 years of age and 1/160 in males over 25 years of age.[3]Unilateral torsion is relatively common,with a higher incidence on the left side.Testicular torsion is typically managed through surgical exploration.Necrotic testes,identified by a black appearance,require orchiectomy.[4]展开更多
BACKGROUND Simultanagnosia is a neurological disorder that impairs an individual's ability to perceive more than one object at a time visually.While the individual may acknowledge the presence of multiple objects ...BACKGROUND Simultanagnosia is a neurological disorder that impairs an individual's ability to perceive more than one object at a time visually.While the individual may acknowledge the presence of multiple objects in his field of view,he cannot generally summarize the overall percept.CASE SUMMARY We describe a case of simultanagnosia in Posterior Cortical Atrophy,evidenced by the Ishihara color test.A 54-year-old woman complained of reading problems despite normal visual acuity and a structural eye exam.The patient failed to identify any of the Ishihara color plates in either eye despite adequate naming of colors.Automated visual field testing showed a homonymous hemianopia.Structural and functional neuroimaging and cerebrospinal fluid analysis were consistent with posterior cortical atrophy.CONCLUSION Simultanagnosia can be tested with the Ishihara pseudoisochromatic plates because the recognition of embedded number patterns in the test requires appreciation of a collection of individual stimuli.展开更多
Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life ...Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life but also imposes substantial socioeconomic burdens.The complex molecular mechanisms driving skeletal muscle atrophy contribute to the absence of effective treatment options.Recent advances in stem cell therapy have positioned it as a promising approach for addressing this condition.This article reviews the molecular mechanisms of muscle atrophy and outlines current therapeutic strategies,focusing on mesenchymal stem cells,induced pluripotent stem cells,and their derivatives.Additionally,the challenges these stem cells face in clinical applications are discussed.A deeper understanding of the regenerative potential of various stem cells could pave the way for breakthroughs in the prevention and treatment of muscle atrophy.展开更多
In clinical specialties focusing on neurological disorders,there is a need for comprehensive and integrated non-invasive,sensitive,and specific testing methods.Both Parkinson's disease and multiple system atrophy ...In clinical specialties focusing on neurological disorders,there is a need for comprehensive and integrated non-invasive,sensitive,and specific testing methods.Both Parkinson's disease and multiple system atrophy are classified asα-synucleinopathies,characterized by abnormal accumulation ofα-synuclein protein,which provides a shared pathological background for their comparative study.In addition,both Parkinson's disease and multiple system atrophy involve neuronal death,a process that may release circulating cell–free DNA(cfDNA)into the bloodstream,leading to specific alterations.This premise formed the basis for investigating cell–free DNA as a potential biomarker.Cellfree DNA has garnered attention for its potential pathological significance,yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully understood.This study investigated the total concentration,nonapoptotic level,integrity,and cellfree DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants,comprising 76 normal controls,62 patients with Parkinson's disease,and 33 patients with multiple system atrophy.In our cohort,75.8%of patients with Parkinson's disease(stage 1–2 of Hoehn&Yahr)and 60.6%of patients with multiple system atrophy(disease duration less than 3 years)were in the early stages.The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic(ROC)analysis,and their association with disease prevalence was examined through logistic regression models,adjusting for confounders such as age,sex,body mass index,and education level.The results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls(P<0.001 for both groups),whereas cell-free DNA relative telomere length was markedly shorter(P=0.003 for Parkinson's disease and P=0.010 for multiple system atrophy).Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson's disease and multiple system atrophy from normal controls.Specifically,higher cell-free DNA integrity was associated with increased risk of Parkinson's disease(odds ratio[OR]:5.72;95%confidence interval[CI]:1.54–24.19)and multiple system atrophy(OR:10.10;95%CI:1.55–122.98).Conversely,longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson's disease(OR:0.16;95%CI:0.04–0.54)and multiple system atrophy(OR:0.10;95%CI:0.01–0.57).These findings suggest that cell-free DNA integrity and cellfree DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson's disease and multiple system atrophy,potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.展开更多
AIM:To identify optical coherence tomography(OCT)features present at the diagnosis of neovascular age-related macular degeneration(nAMD)that could predict retinal atrophy(RA)and visual performance in patients treated ...AIM:To identify optical coherence tomography(OCT)features present at the diagnosis of neovascular age-related macular degeneration(nAMD)that could predict retinal atrophy(RA)and visual performance in patients treated with intravitreal aflibercept.METHODS:OCT data collected at the time of nAMD diagnosis(T0),after the first(T1)and third(T2)intravitreal aflibercept injection,and 5y post-diagnosis(T3)were analyzed.The study included 46 eyes from patients undergoing treatment.The association of OCT features with RA and visual acuity(VA)development over time were evaluated.RESULTS:Patients with RA at T3 exhibited worse VA(35.19±5.7 vs 8.90±2.3,P<0.001)and a lower rate of improvement or stability at T2(90.48%vs 56.00%,P=0.019)and T3(85.71%vs 8.00%,P<0.001).The development of RA at T3 was linked with type 2 macular neovascularization(MNV;4.76%vs 36.00%,P=0.013),thinner outer nuclear layer(ONL,88.89±7.82μm vs 71.38±14.14μm,P=0.033),presence of intraretinal fluid(IRF,42.86%vs 80.00%,P=0.014),presence of IRF without subretinal fluid at T0(SRF,4.76%vs 32.00%,P=0.027),and reduced central foveal thickness at T3(CFT,190.14±22.79μm vs 124.32±14.35μm,P<0.001).The presence of SRF with or without IRF at the diagnosis was comparable between the two groups(90.48%vs 68.00%;P=0.084).CONCLUSION:Type 2 MNV,reduces ONL and CFT,and IRF presence at baseline may signal a higher risk of RA in treatment-naive nAMD patients,underscoring the importance of these OCT features in early risk assessment and management strategies.展开更多
AIM:To determine the differences in levels of systemic C-reactive protein(CRP)in patients with geographic atrophy(GA)and sex-based differences in CRP levels.METHODS:Blood samples from patients with GA and controls wer...AIM:To determine the differences in levels of systemic C-reactive protein(CRP)in patients with geographic atrophy(GA)and sex-based differences in CRP levels.METHODS:Blood samples from patients with GA and controls were collected in a prospective age-related macular degeneration(AMD)registry from August 2014 to June 2021.AMD was confirmed using multimodal imaging and the Beckman and Consensus of Atrophy Meeting criteria for GA.High-sensitivity serum CRP levels were measured using an automated nephelometer.A non-parametric(rank-based)linear regression model was fit with an interaction between sex and GA.RESULTS:There were 97 GA patients and 139 controls,with females comprising 55%and 66%of each cohort,respectively.There is no difference in CRP between cases and controls,with a median(interquartile range)of 1.2(0.6-2.6)mg/L in GA patients versus 1.3(0.8–2.9)mg/L in controls(P=0.52).Although females had higher CRP levels compared to males in both the GA and control groups,this difference did not reach statistical significance after adjustment for multiple comparisons.CONCLUSION:There is no significant difference in systemic CRP levels between GA cases and controls.展开更多
基金supported by Basic Science Research Program through the National Research Foundation of Korea (NRF)funded by the Ministry of Education (NRF-2016R1D1A1B01014260)
文摘The purpose of this study was to investigate the intensity-specific regenerative effects of microcurrent therapy on gastrocnemius muscle atrophy induced by cast-immobilization in rabbits. Fifteen rabbits were randomly allocated to 3 groups after cast removal: cast-immobilization and sham microcurrent therapy for 2 weeks(group 1); castimmobilization and microcurrent therapy(25 μA) for 2 weeks(group 2); cast-immobilization and microcurrent therapy(5,000 μA) for 2 weeks(group 3). Clinical parameters [calf circumference, compound muscle action potential(CMAP) of the tibial nerve, thickness of gastrocnemius muscle], cross sectional area of gastrocnemius muscle fibres,and immunohistochemistry was evaluated. The clinical parameters representing mean atrophic changes in group 2 were significantly lower than those in group 3. The cross sectional area of the gastrocnemius muscle fibres and immunohistochemical parameters in group 2 were significantly greater than those in group 3. The results showed that low-intensity microcurrent therapy can more effectively promote regeneration in atrophied gastrocnemius muscle than high-intensity microcurrent therapy.
基金funded by research grant from National Natural Science Foundation of China(32171135).
文摘Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.
基金funded by research grants from the National Natural Science Foundation of China (32171135 and 32371168)。
文摘Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in this process.Methods: 8-week-old male C57BL/6J mice were carried out combined exercise for 10 weeks. One week before the end of the intervention, mice underwent cast immobilization. Additionally, to investigate the potential mechanism in exercise-induced protection of skeletal muscle, mice in the exercise preconditioning group were administered TC-E-5003(an inhibitor of Prmt1 enzymatic activity). Exercise performance, muscle mass, and the cross-sectional area(CSA) of muscle fibers were analyzed. Besides, Prmt1 and Sestrin1(Sesn1) were either overexpressed or inhibited in C2C12 myotubes to elucidate the underlying mechanism.Results: Exercise preconditioning not only significantly improved muscle mass and motor ability in immobilized mice but also inhibited excessive activation of degradation pathways and enhanced protein synthesis. Importantly, Prmt1 mediated the protective effects of exercise preconditioning on muscle atrophy. Mechanistically,Prmt1 regulated the p38 mitogen-activated protein kinase(p38)/activating transcription factor 2(ATF2)pathway, which modulates Sesn1 expression. Sesn1 acts as a downstream of Prmt1 and ATF2, contributing to the myoblast differentiation and skeletal muscle regeneration through AMP-Activated protein kinase α2(AMPKα2)/transcriptional co-activator PPAR-γ co-activator-1 α(PGC-1α) signaling pathway.Conclusions: Taken together, our results highlighted the effectiveness of exercise preconditioning in preventing muscle atrophy via the Prmt1-Sesn1 pathway.
基金Supported by National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022,and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.CIFMS 2021-1-I2M-003Undergraduate Innovation Program,No.2024dcxm025.
文摘Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.
基金supported by STI2030-Major Project,No,2021ZD0204200(to LX).
文摘Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.
基金supported by Felipe Fiorellino´s Scientific Foundation.
文摘Objectives:Restore muscular trophism and voluntary contractile capacity through cell therapy in atrophied muscles in SCI patients.Setting:Out Patient Treatment,Universidad Maimonides,Buenos Aires,Argentina.Methods:After receiving spinal cord cell therapy and intensive rehabilitation,7 chronic complete spinal cord injury(SCI)patients(4 people with paraplegia and 3 people with quadriplegia)regained muscular electrical activity in previously denervated territories.However,signs of severe muscular atrophy persisted.Looking to reverse chronic muscular atrophy,atrophied muscles with electrical activity were implanted with autologous type 1 macrophages(Mo1)and autologous tissue-specific T helper 1 Cells(Th1)associated with autologous muscular progenitor cells(MPC).The Mo1 and Th1 used cells were named Effector Cells(EC).Each muscle received between 6 to 8 implants,one every 6 weeks.Cellular therapy was combined with intensive rehabilitation program.Results:Sonogram and histological signs of recovery started eight weeks after the first implant.Sonograms showed progressively muscle volume increasing and gradually replacement of hyperechogenic muscle tissue by hypoechogenic muscle bands(resembling normalmuscular structure).New bands were distributed parallel to the main muscle axis,along the entire muscular length.Histological samples of hypoechogenic bands showed new and normal muscular tissue.Changes were seen in 7/7 patients.Non-significant side events were detected in any patient over the 24 months of follow up.Conclusions:The results presented here suggest that the combination of immune and regenerative cell therapy may play an important therapeutic role in clinical and histological recovery of chronic muscular atrophy.
基金supported by the Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai,No.CCTS-2022205the“Double World-Class Project”of Shanghai Jiaotong University School of Medicine(both to JZ)。
文摘Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
基金supported by the Faculty Research Fund(Faculty of Medicine&Health Science,Keele University)Career Development Award–(April 2022)(to SJB)。
文摘Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and atrophy.The genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene therapies.SMA was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between individuals.Now,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice versa.Additionally,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
基金Supported by The New Faculty Research Grant of Pusan National University,2023The Research Grant of the Chungbuk National University in 2023.
文摘BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO_(2) laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.
文摘Segmental atrophy(SA)of the liver is a rare,often underrecognized,benign condition that presents as a mass lesion,mimicking a neoplasm,which poses a significant diagnostic challenge.Given its rarity,only a limited number of case reports and series have been published,resulting in sparse literature on the entity.This review aims to summarize the clinicopathologic and diagnostic features of SA and thus improve its recognition.
基金National Natural Science Foundation of China,Grant/Award Number:81970219, 82170261, 82200289 and 82370283National Key Research and Development Program of China,Grant/Award Number:2023YFF0724900。
文摘Background : Cancer-associated cardiac cachexia(CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods : This study established CACC models in C57BL/6J and BALB/c mice using orthotopic, intra-abdominal, and hematogenous metastatic tumor induction. Multimodal cardiac assessments, including echocardiography, transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis, and ex vivo cardiomyocyte contractility assays, were systematically applied. Results : Metastatic burden triggered CACC characterized by cardiac mass reduction, epicardial fat depletion, interstitial fibrosis, and electrocardiographic abnormalities. Histopathological analysis revealed cardiomyocyte atrophy, myofibrillar disarray, mitochondrial dysfunction, and ubiquitin-mediated Myh6 degradation via Mu RF-1, accompanied by compensatory Myh7 upregulation. These findings mechanistically link tumor-induced cachexia to cardiac dysfunction through contractile protein remodeling. Conclusion : This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer-related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration.
基金supported by the National Natural Science Foundation of China(82003447,32202023)the Natural Science Foundation of Shandong Province(ZR2021QC177)the Young Scholars Program of Shandong University(2018WLJH33,2018WLJH34)。
文摘Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still unclear.In this study,the male C57BL/6J mice were fed a high-fat diet(HFD)for 12 weeks to induce obesity,and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks.The results showed that KO treatment reduced body weight,fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice.Importantly,KO treatment attenuated skeletal muscle atrophy in HFD-fed mice,as evidenced by preserving skeletal muscle mass,average myofiber cross-sectional area and grip strength.KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle.Additionally,KO treatment inhibited the transcriptional activities of nuclear factor-κB(NF-κB)p65 and forkhead box O 3a(FoxO3a),and then down-regulated muscle atrophy F-box(MAFbx)and muscle-specific RING finger protein 1(MuRF1)protein levels in skeletal muscle from HFD-fed mice.KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway.Furthermore,KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1αpathway.Collectively,KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.
基金thank the staff of the accredited animal facility of the laboratory of anatomy,Histology and Embryology of Aristotle University of Thessaloniki’s veterinary school for their assistance in animal handling and care.
文摘BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increase re-tear rates.AIM To investigate the potential inhibitory effects of alpha-tocopherol(vitamin E)and OTR-4131 on muscle atrophy,fatty infiltration,and fibrosis in rotator cuff muscles following a massive RCT using a Wistar rat model,and establish a standardized methodology for evaluating potential therapeutic agents.METHODS This protocol outlines a controlled animal study using 40 male Wistar rats,randomized into five groups.The experimental groups will receive either systemic administration of alpha-tocopherol or local administration of OTR-4131 via intramuscular injection into the supraspinatus and infraspinatus muscles.Two sham groups will receive systemic and local saline injections respectively,while a control group will undergo no intervention.The interventions will be administered after surgical transection of the supraspinatus and infraspinatus tendons.Outcomes will be assessed via wet muscle weight measurements,muscle fiber diameter,fatty infiltration percentage,and fibrosis evaluation using histological methods.RESULTS The study anticipates that alpha-tocopherol and OTR-4131 will reduce muscle atrophy,fatty infiltration,and fibrosis compared to control and sham groups,supporting their potential protective role in rotator cuff muscle degeneration.CONCLUSION The results are expected to improve the understanding on the role of alpha-tocopherol and OTR-4131 in rotator cuff muscle protection after massive RCT and may serve as a foundation for further preclinical and clinical research aimed at improving rotator cuff repair outcomes.
基金supported by the National Natural Science Foundation of China(82371709).
文摘Testicular torsion is a urological emergency that requires prompt diagnosis and treatment,accounting for 10%-15%of cases of acute scrotum.[1]It occurs most frequently during the perinatal period and adolescence and can occur at any age.[2]The incidence of testicular torsion is 1/4,000 in males under 25 years of age and 1/160 in males over 25 years of age.[3]Unilateral torsion is relatively common,with a higher incidence on the left side.Testicular torsion is typically managed through surgical exploration.Necrotic testes,identified by a black appearance,require orchiectomy.[4]
文摘BACKGROUND Simultanagnosia is a neurological disorder that impairs an individual's ability to perceive more than one object at a time visually.While the individual may acknowledge the presence of multiple objects in his field of view,he cannot generally summarize the overall percept.CASE SUMMARY We describe a case of simultanagnosia in Posterior Cortical Atrophy,evidenced by the Ishihara color test.A 54-year-old woman complained of reading problems despite normal visual acuity and a structural eye exam.The patient failed to identify any of the Ishihara color plates in either eye despite adequate naming of colors.Automated visual field testing showed a homonymous hemianopia.Structural and functional neuroimaging and cerebrospinal fluid analysis were consistent with posterior cortical atrophy.CONCLUSION Simultanagnosia can be tested with the Ishihara pseudoisochromatic plates because the recognition of embedded number patterns in the test requires appreciation of a collection of individual stimuli.
基金Suzhou Science and Technology Development Planning Project,No.SYW2024048National Natural Science Foundation of China,No.81901933Major Natural Science Research Projects in Universities of Jiangsu Province,No.24KJA310007.
文摘Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life but also imposes substantial socioeconomic burdens.The complex molecular mechanisms driving skeletal muscle atrophy contribute to the absence of effective treatment options.Recent advances in stem cell therapy have positioned it as a promising approach for addressing this condition.This article reviews the molecular mechanisms of muscle atrophy and outlines current therapeutic strategies,focusing on mesenchymal stem cells,induced pluripotent stem cells,and their derivatives.Additionally,the challenges these stem cells face in clinical applications are discussed.A deeper understanding of the regenerative potential of various stem cells could pave the way for breakthroughs in the prevention and treatment of muscle atrophy.
基金supported by the National Key Research and Development Program of China,No.2021YFC2501205(to YC)the Science and Technology Innovation 2030 project,No.2021ZD0201101(to YC)+1 种基金the National Natural Science Foundation of China,Nos.82201409(to YL),82201401(to CH)the Xuanwu Youth Development Project,No.QNPY2021011(to CH)。
文摘In clinical specialties focusing on neurological disorders,there is a need for comprehensive and integrated non-invasive,sensitive,and specific testing methods.Both Parkinson's disease and multiple system atrophy are classified asα-synucleinopathies,characterized by abnormal accumulation ofα-synuclein protein,which provides a shared pathological background for their comparative study.In addition,both Parkinson's disease and multiple system atrophy involve neuronal death,a process that may release circulating cell–free DNA(cfDNA)into the bloodstream,leading to specific alterations.This premise formed the basis for investigating cell–free DNA as a potential biomarker.Cellfree DNA has garnered attention for its potential pathological significance,yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully understood.This study investigated the total concentration,nonapoptotic level,integrity,and cellfree DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants,comprising 76 normal controls,62 patients with Parkinson's disease,and 33 patients with multiple system atrophy.In our cohort,75.8%of patients with Parkinson's disease(stage 1–2 of Hoehn&Yahr)and 60.6%of patients with multiple system atrophy(disease duration less than 3 years)were in the early stages.The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic(ROC)analysis,and their association with disease prevalence was examined through logistic regression models,adjusting for confounders such as age,sex,body mass index,and education level.The results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls(P<0.001 for both groups),whereas cell-free DNA relative telomere length was markedly shorter(P=0.003 for Parkinson's disease and P=0.010 for multiple system atrophy).Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson's disease and multiple system atrophy from normal controls.Specifically,higher cell-free DNA integrity was associated with increased risk of Parkinson's disease(odds ratio[OR]:5.72;95%confidence interval[CI]:1.54–24.19)and multiple system atrophy(OR:10.10;95%CI:1.55–122.98).Conversely,longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson's disease(OR:0.16;95%CI:0.04–0.54)and multiple system atrophy(OR:0.10;95%CI:0.01–0.57).These findings suggest that cell-free DNA integrity and cellfree DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson's disease and multiple system atrophy,potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.
文摘AIM:To identify optical coherence tomography(OCT)features present at the diagnosis of neovascular age-related macular degeneration(nAMD)that could predict retinal atrophy(RA)and visual performance in patients treated with intravitreal aflibercept.METHODS:OCT data collected at the time of nAMD diagnosis(T0),after the first(T1)and third(T2)intravitreal aflibercept injection,and 5y post-diagnosis(T3)were analyzed.The study included 46 eyes from patients undergoing treatment.The association of OCT features with RA and visual acuity(VA)development over time were evaluated.RESULTS:Patients with RA at T3 exhibited worse VA(35.19±5.7 vs 8.90±2.3,P<0.001)and a lower rate of improvement or stability at T2(90.48%vs 56.00%,P=0.019)and T3(85.71%vs 8.00%,P<0.001).The development of RA at T3 was linked with type 2 macular neovascularization(MNV;4.76%vs 36.00%,P=0.013),thinner outer nuclear layer(ONL,88.89±7.82μm vs 71.38±14.14μm,P=0.033),presence of intraretinal fluid(IRF,42.86%vs 80.00%,P=0.014),presence of IRF without subretinal fluid at T0(SRF,4.76%vs 32.00%,P=0.027),and reduced central foveal thickness at T3(CFT,190.14±22.79μm vs 124.32±14.35μm,P<0.001).The presence of SRF with or without IRF at the diagnosis was comparable between the two groups(90.48%vs 68.00%;P=0.084).CONCLUSION:Type 2 MNV,reduces ONL and CFT,and IRF presence at baseline may signal a higher risk of RA in treatment-naive nAMD patients,underscoring the importance of these OCT features in early risk assessment and management strategies.
基金Supported by the Greenwald Family Research Fund,a Research to Prevent Blindness grant to the Department of Ophthalmology,University of Colorado,the Frederic C.Hamilton Macular Degeneration Center,Sue Anschutz-Rodgers Eye Center Research Fund,NIH/NCATS Colorado CTSA(No.UL1 TR002535)in part by the National Eye Institute of the National Institutes of Health[No.R01EY032456(AML)].
文摘AIM:To determine the differences in levels of systemic C-reactive protein(CRP)in patients with geographic atrophy(GA)and sex-based differences in CRP levels.METHODS:Blood samples from patients with GA and controls were collected in a prospective age-related macular degeneration(AMD)registry from August 2014 to June 2021.AMD was confirmed using multimodal imaging and the Beckman and Consensus of Atrophy Meeting criteria for GA.High-sensitivity serum CRP levels were measured using an automated nephelometer.A non-parametric(rank-based)linear regression model was fit with an interaction between sex and GA.RESULTS:There were 97 GA patients and 139 controls,with females comprising 55%and 66%of each cohort,respectively.There is no difference in CRP between cases and controls,with a median(interquartile range)of 1.2(0.6-2.6)mg/L in GA patients versus 1.3(0.8–2.9)mg/L in controls(P=0.52).Although females had higher CRP levels compared to males in both the GA and control groups,this difference did not reach statistical significance after adjustment for multiple comparisons.CONCLUSION:There is no significant difference in systemic CRP levels between GA cases and controls.
