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 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
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
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
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
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 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
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
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
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
Objective:To evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.Methods:This ...Objective:To evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.Methods:This was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control(n=40)and intervention(n=40)groups.The control group received conventional orthopedic treatment,whereas the intervention group received TEAS and conventional treatment.The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks.The primary out-comes were muscle thickness(MT)and cross-sectional area(CSA)of the rectus femoris and gastroc-nemius muscles,whereas the secondary outcome measure was echo intensity(EI).Data were collected before the fixation operations(baseline assessment)and 4 and 8 weeks after intervention.Results:Compared with baseline,the MT and CSA were reduced in both groups by the end of treatment,whereas EI increased in both groups.At week 4,the reduction in the rectus femoris CSA in the inter-vention group was significantly lower than that in the control group(P=0.02);however,the between-group differences in the MT and EI(all P>0.05)were not significant.No serious adverse events were observed in either group.Conclusion:Our study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA.Because this was only a pilot trial,subsequent studies will need longer follow-ups and larger sample sizes.展开更多
BACKGROUND The pathogenesis of non-ampullary duodenal epithelial tumors(NADETs)is not fully understood.NADETs that express gastric-type mucin phenotypes(GNADETs)are noteworthy because of their high malignancy.Gastric ...BACKGROUND The pathogenesis of non-ampullary duodenal epithelial tumors(NADETs)is not fully understood.NADETs that express gastric-type mucin phenotypes(GNADETs)are noteworthy because of their high malignancy.Gastric foveolar metaplasia,from which G-NADETs originate,protects the duodenal mucosa from gastric acidity.As gastric acid secretion is affected by endoscopic gastric mucosal atrophy(EGMA),we hypothesized that EGMA would be associated with GNADETs.AIM To evaluate the association between EGMA and the occurrence of G-NADETs.METHODS This cross-sectional retrospective study investigated the relationship between EGMA and NADETs in 134 patients.The duodenum was divided into parts 1(bulb),2(superior duodenal angle to the papilla),and 3(anal side of the papilla to the horizontal part).The effects of gastric acidity and presence of Brunner’s glands were considered.EGMA was divided into types C(no or mild atrophy)and O(severe atrophy).Mucin phenotype expressions in NADETs were divided into gastric,intestinal,gastrointestinal,and unclassifiable.RESULTS When NADETs were classified according to EGMA,105 were classified as type C and 29 as type O.G-NADETs were present in 11.9%(16 cases)of all cases,and all 16 cases were of type C.Among G-NADETs,93.8%(15 cases)were present in part 1 or 2.There was an association between G-NADETs and type C in part 1,and 50.0%(eight of 16 cases)of G-NADETs were associated with a current or previous Helicobacter pylori infection status.Additionally,all eight cases occurred in part 1.CONCLUSION G-NADETs were significantly associated with type C.Gastric acidity and Brunner's gland growth may be associated with G-NADETs.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
Objective:To analyze the therapeutic effect of Yizhi Xingnao Decoction+Yizhi Pill on cerebral atrophy and Alzheimer’s disease(AD).Methods:Ninety-two patients with cerebral atrophy and AD who were admitted to the hosp...Objective:To analyze the therapeutic effect of Yizhi Xingnao Decoction+Yizhi Pill on cerebral atrophy and Alzheimer’s disease(AD).Methods:Ninety-two patients with cerebral atrophy and AD who were admitted to the hospital from September 2022 to September 2024 were selected and randomly divided into two groups using a random number table.The traditional Chinese medicine(TCM)group was treated with Yizhi Xingnao Decoction+Yizhi Pill,while the western medicine group was treated with Donepezil Hydrochloride.Indicators such as total effective rate,TCM syndrome score,dementia degree score,and cognitive function score were compared between the two groups.Results:The total effective rate of the TCM group was higher than that of the Western medicine group(P<0.05).After treatment,the TCM syndrome score,dementia degree score,and cognitive function score of the TCM group were all lower than those of the Western medicine group(P<0.05).Conclusion:Yizhi Xingnao Decoction+Yizhi Pill can improve the clinical efficacy of patients with cerebral atrophy and AD,reduce disease symptoms and dementia severity,and improve patients’cognitive function.展开更多
AIM:To investigate the factors influencing meibomian gland atrophy(MGA)in children with allergic conjunctivitis(AC).METHODS:In this cross-sectional study,60 children with AC aged 6-17y and 20 age-matched children with...AIM:To investigate the factors influencing meibomian gland atrophy(MGA)in children with allergic conjunctivitis(AC).METHODS:In this cross-sectional study,60 children with AC aged 6-17y and 20 age-matched children without signs or symptoms of ocular surface dysfunction were included.Information on the duration of AC,untreated time,electronic screen time(EST),outdoor exercise time,body mass index(BMI),and frequency of eye rubbing was collected using a health history form.The Standard Patient Evaluation of Eye Dryness(SPEED)score was used for dry eye assessment.Images of the meibomian glands(MGs)were obtained using Keratograph 5M,and the rate of meibomian gland atrophy(MGAR)was calculated using Image J.All subjects underwent routine eye examinations.RESULTS:The average age of the AC group was 10.43±2.75y(range 6-17y)and 10.35±3.42y(range 6-14y)in the control group.The MGAR in the AC group was 33.42%±11.91%,significantly higher than that in the control group(18.10%±11.74%,P<0.001).Moreover,the MGAR in younger children(aged 12 and below)was significantly higher than in older children(P<0.05).Multi-factor linear regression analysis revealed that EST non-projector was a risk factor for MGAR(β=0.332,95%CI 0.04-0.22,P=0.004),while outdoor exercise time was a protective factor against MGAR(β=-0.407,95%CI-0.39 to-0.10,P=0.001).The untreated time of AC was identified as a risk factor for MGAR(β=0.24,95%CI 0.07-1.98,P=0.037),and the frequency of eye rubbing was associated with MG distortion score(P=0.00).CONCLUSION:Children with AC exhibit exacerbate MGA,with the degree of atrophy worsening as the untreated time of AC prolongs.Children under 12 years old show a higher MGAR,and EST non-projector negatively impacts MGA,while increased outdoor exercise time acts as a protective factor against MGA.展开更多
Background:The aim of this study was to analyze the bi-directional causal relation-ship between lipid profile and characteristics related to muscle atrophy by using a bi-directional Mendelian randomization(MR)analysis...Background:The aim of this study was to analyze the bi-directional causal relation-ship between lipid profile and characteristics related to muscle atrophy by using a bi-directional Mendelian randomization(MR)analysis.Methods:The appendicular lean mass(ALM),whole body fat-free mass(WBFFM)and trunk fat-free mass(TFFM)were used as genome-wide association study(GWAS)data for evaluating muscle mass;the usual walking pace(UWP)and low grip strength(LGS)were used as GWAS data for evaluating muscle strength;and the triglycerides(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL),low density lipo-protein cholesterol(LDL),apolipoprotein A-1(Apo A-1),and apolipoprotein B(Apo B)were used as GWAS data for evaluating lipid profile.For specific investigations,we mainly employed inverse variance weighting for causal estimation and MR-Egger for pleiotropy analysis.Results:MR results showed that the lipid profile predicted by genetic variants was negatively correlated with muscle mass,positively correlated with UWP,and was not causally correlated with LGS.On the other hand,the muscle mass predicted by genetic variants was negatively correlated with lipid profile,the UWP predicted by genetic variants was mainly positively correlated with lipid profile,while the LGS pre-dicted by genetic variants had no relevant causal relationship with lipid profile.Conclusions:Findings of this MR analysis suggest that hyperlipidemia may affect muscle mass and lead to muscle atrophy,but has no significant effect on muscle strength.On the other hand,increased muscle mass may reduce the incidence of dyslipidemia.展开更多
Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasyn...Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) aggregates.These a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble aggregates.Oligomeric forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.展开更多
Spinal muscular atrophy(SMA)is a genetic disorder that primarily affects infants and leads to muscle weakness,atrophy,and paralysis.The main cause is the homozygous mutation or deletion of the SMN1 gene,resulting in i...Spinal muscular atrophy(SMA)is a genetic disorder that primarily affects infants and leads to muscle weakness,atrophy,and paralysis.The main cause is the homozygous mutation or deletion of the SMN1 gene,resulting in inadequate levels of the survival motor neuron(SMN)protein.Approved treatments focus on restoring SMN levels through various approaches,but there is a need for“SMN-independent”therapies that target other pathological processes.Skeletal muscle is closely involved in SMA pathology,with impaired muscle function observed before motor neuron degeneration.Studies have revealed that SMN loss leads to skeletal muscle mitochondrial structural abnormalities,impaired respiration,and accumulation of reactive oxygen species.展开更多
BACKGROUND Akt plays diverse roles in humans.It is involved in the pathogenesis of type 2 diabetes mellitus(T2DM),which is caused by insulin resistance.Akt also plays a vital role in human platelet activation.Furtherm...BACKGROUND Akt plays diverse roles in humans.It is involved in the pathogenesis of type 2 diabetes mellitus(T2DM),which is caused by insulin resistance.Akt also plays a vital role in human platelet activation.Furthermore,the hippocampus is closely associated with memory and learning,and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without dementia.AIM To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients.METHODS Platelet-rich plasma(PRP)was prepared from the venous blood of patients with T2DM or age-matched controls.The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt,p38 mitogen-activated protein(MAP)kinase and glyceraldehyde 3-phosphate dehydrogenase(GAPDH).Phosphorylation levels were quantified by densitometric analysis.Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer’s disease on magnetic resonance imaging,which proposes the Z-score as a parameter that reflects hippocampal volume.RESULTS The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects,whereas the levels of phosphorylated Akt corrected with GAPDH were not.However,this relationship was not observed in the control patients.CONCLUSION These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients.Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.展开更多
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 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 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 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.
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.
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.
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 funded project(HYZHX M05005)in the field of space medical experiments of manned spaceflight engineering.
文摘Objective:To evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.Methods:This was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control(n=40)and intervention(n=40)groups.The control group received conventional orthopedic treatment,whereas the intervention group received TEAS and conventional treatment.The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks.The primary out-comes were muscle thickness(MT)and cross-sectional area(CSA)of the rectus femoris and gastroc-nemius muscles,whereas the secondary outcome measure was echo intensity(EI).Data were collected before the fixation operations(baseline assessment)and 4 and 8 weeks after intervention.Results:Compared with baseline,the MT and CSA were reduced in both groups by the end of treatment,whereas EI increased in both groups.At week 4,the reduction in the rectus femoris CSA in the inter-vention group was significantly lower than that in the control group(P=0.02);however,the between-group differences in the MT and EI(all P>0.05)were not significant.No serious adverse events were observed in either group.Conclusion:Our study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA.Because this was only a pilot trial,subsequent studies will need longer follow-ups and larger sample sizes.
文摘BACKGROUND The pathogenesis of non-ampullary duodenal epithelial tumors(NADETs)is not fully understood.NADETs that express gastric-type mucin phenotypes(GNADETs)are noteworthy because of their high malignancy.Gastric foveolar metaplasia,from which G-NADETs originate,protects the duodenal mucosa from gastric acidity.As gastric acid secretion is affected by endoscopic gastric mucosal atrophy(EGMA),we hypothesized that EGMA would be associated with GNADETs.AIM To evaluate the association between EGMA and the occurrence of G-NADETs.METHODS This cross-sectional retrospective study investigated the relationship between EGMA and NADETs in 134 patients.The duodenum was divided into parts 1(bulb),2(superior duodenal angle to the papilla),and 3(anal side of the papilla to the horizontal part).The effects of gastric acidity and presence of Brunner’s glands were considered.EGMA was divided into types C(no or mild atrophy)and O(severe atrophy).Mucin phenotype expressions in NADETs were divided into gastric,intestinal,gastrointestinal,and unclassifiable.RESULTS When NADETs were classified according to EGMA,105 were classified as type C and 29 as type O.G-NADETs were present in 11.9%(16 cases)of all cases,and all 16 cases were of type C.Among G-NADETs,93.8%(15 cases)were present in part 1 or 2.There was an association between G-NADETs and type C in part 1,and 50.0%(eight of 16 cases)of G-NADETs were associated with a current or previous Helicobacter pylori infection status.Additionally,all eight cases occurred in part 1.CONCLUSION G-NADETs were significantly associated with type C.Gastric acidity and Brunner's gland growth may be associated with G-NADETs.
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.
文摘Objective:To analyze the therapeutic effect of Yizhi Xingnao Decoction+Yizhi Pill on cerebral atrophy and Alzheimer’s disease(AD).Methods:Ninety-two patients with cerebral atrophy and AD who were admitted to the hospital from September 2022 to September 2024 were selected and randomly divided into two groups using a random number table.The traditional Chinese medicine(TCM)group was treated with Yizhi Xingnao Decoction+Yizhi Pill,while the western medicine group was treated with Donepezil Hydrochloride.Indicators such as total effective rate,TCM syndrome score,dementia degree score,and cognitive function score were compared between the two groups.Results:The total effective rate of the TCM group was higher than that of the Western medicine group(P<0.05).After treatment,the TCM syndrome score,dementia degree score,and cognitive function score of the TCM group were all lower than those of the Western medicine group(P<0.05).Conclusion:Yizhi Xingnao Decoction+Yizhi Pill can improve the clinical efficacy of patients with cerebral atrophy and AD,reduce disease symptoms and dementia severity,and improve patients’cognitive function.
基金Supported by the Natural Science Foundation of the Zhejiang Province(No.LGD22H120002).
文摘AIM:To investigate the factors influencing meibomian gland atrophy(MGA)in children with allergic conjunctivitis(AC).METHODS:In this cross-sectional study,60 children with AC aged 6-17y and 20 age-matched children without signs or symptoms of ocular surface dysfunction were included.Information on the duration of AC,untreated time,electronic screen time(EST),outdoor exercise time,body mass index(BMI),and frequency of eye rubbing was collected using a health history form.The Standard Patient Evaluation of Eye Dryness(SPEED)score was used for dry eye assessment.Images of the meibomian glands(MGs)were obtained using Keratograph 5M,and the rate of meibomian gland atrophy(MGAR)was calculated using Image J.All subjects underwent routine eye examinations.RESULTS:The average age of the AC group was 10.43±2.75y(range 6-17y)and 10.35±3.42y(range 6-14y)in the control group.The MGAR in the AC group was 33.42%±11.91%,significantly higher than that in the control group(18.10%±11.74%,P<0.001).Moreover,the MGAR in younger children(aged 12 and below)was significantly higher than in older children(P<0.05).Multi-factor linear regression analysis revealed that EST non-projector was a risk factor for MGAR(β=0.332,95%CI 0.04-0.22,P=0.004),while outdoor exercise time was a protective factor against MGAR(β=-0.407,95%CI-0.39 to-0.10,P=0.001).The untreated time of AC was identified as a risk factor for MGAR(β=0.24,95%CI 0.07-1.98,P=0.037),and the frequency of eye rubbing was associated with MG distortion score(P=0.00).CONCLUSION:Children with AC exhibit exacerbate MGA,with the degree of atrophy worsening as the untreated time of AC prolongs.Children under 12 years old show a higher MGAR,and EST non-projector negatively impacts MGA,while increased outdoor exercise time acts as a protective factor against MGA.
基金Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2021A1515220030Hunan Provincial Clinical Medical Technology Innovation Guiding Project,Grant/Award Number:2020SK53307+2 种基金Hunan Provincial Health Commission,Grant/Award Number:20201902Natural Science Foundation of Hunan Province,Grant/Award Number:2020JJ8043Project of Hunan Provincial Health,Grant/Award Number:c2019133。
文摘Background:The aim of this study was to analyze the bi-directional causal relation-ship between lipid profile and characteristics related to muscle atrophy by using a bi-directional Mendelian randomization(MR)analysis.Methods:The appendicular lean mass(ALM),whole body fat-free mass(WBFFM)and trunk fat-free mass(TFFM)were used as genome-wide association study(GWAS)data for evaluating muscle mass;the usual walking pace(UWP)and low grip strength(LGS)were used as GWAS data for evaluating muscle strength;and the triglycerides(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL),low density lipo-protein cholesterol(LDL),apolipoprotein A-1(Apo A-1),and apolipoprotein B(Apo B)were used as GWAS data for evaluating lipid profile.For specific investigations,we mainly employed inverse variance weighting for causal estimation and MR-Egger for pleiotropy analysis.Results:MR results showed that the lipid profile predicted by genetic variants was negatively correlated with muscle mass,positively correlated with UWP,and was not causally correlated with LGS.On the other hand,the muscle mass predicted by genetic variants was negatively correlated with lipid profile,the UWP predicted by genetic variants was mainly positively correlated with lipid profile,while the LGS pre-dicted by genetic variants had no relevant causal relationship with lipid profile.Conclusions:Findings of this MR analysis suggest that hyperlipidemia may affect muscle mass and lead to muscle atrophy,but has no significant effect on muscle strength.On the other hand,increased muscle mass may reduce the incidence of dyslipidemia.
基金supported by Deutsche ForschungsgemeinschaftEXC 2145 SyNergyGrant No.390857198 (to PL)。
文摘Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) aggregates.These a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble aggregates.Oligomeric forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.
基金supported by AFM-Telethon2013/Project 16662(to CB).
文摘Spinal muscular atrophy(SMA)is a genetic disorder that primarily affects infants and leads to muscle weakness,atrophy,and paralysis.The main cause is the homozygous mutation or deletion of the SMN1 gene,resulting in inadequate levels of the survival motor neuron(SMN)protein.Approved treatments focus on restoring SMN levels through various approaches,but there is a need for“SMN-independent”therapies that target other pathological processes.Skeletal muscle is closely involved in SMA pathology,with impaired muscle function observed before motor neuron degeneration.Studies have revealed that SMN loss leads to skeletal muscle mitochondrial structural abnormalities,impaired respiration,and accumulation of reactive oxygen species.
基金Research Funding for Longevity Science from The National Center for Geriatrics and Gerontology,Japan,No.19-21and No.22-19.
文摘BACKGROUND Akt plays diverse roles in humans.It is involved in the pathogenesis of type 2 diabetes mellitus(T2DM),which is caused by insulin resistance.Akt also plays a vital role in human platelet activation.Furthermore,the hippocampus is closely associated with memory and learning,and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without dementia.AIM To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients.METHODS Platelet-rich plasma(PRP)was prepared from the venous blood of patients with T2DM or age-matched controls.The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt,p38 mitogen-activated protein(MAP)kinase and glyceraldehyde 3-phosphate dehydrogenase(GAPDH).Phosphorylation levels were quantified by densitometric analysis.Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer’s disease on magnetic resonance imaging,which proposes the Z-score as a parameter that reflects hippocampal volume.RESULTS The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects,whereas the levels of phosphorylated Akt corrected with GAPDH were not.However,this relationship was not observed in the control patients.CONCLUSION These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients.Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.
