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1.
Neuroimage ; 297: 120701, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38914210

RESUMO

Due to a high degree of symptom overlap in the early stages, with movement disorders predominating, Parkinson's disease (PD) and multiple system atrophy (MSA) may exhibit a similar decline in motor areas, yet they differ in their spread throughout the brain, ultimately resulting in two distinct diseases. Drawing upon neuroimaging analyses and altered motor cortex excitability, potential diffusion mechanisms were delved into, and comparisons of correlations across distinct disease groups were conducted in a bid to uncover significant pathological disparities. We recruited thirty-five PD, thirty-seven MSA, and twenty-eight matched controls to conduct clinical assessments, electromyographic recording, and magnetic resonance imaging scanning during the "on medication" state. Patients with neurodegeneration displayed a widespread decrease in electrophysiology in bilateral M1. Brain function in early PD was still in the self-compensatory phase and there was no significant change. MSA patients demonstrated an increase in intra-hemispheric function coupled with a decrease in diffusivity, indicating a reduction in the spread of neural signals. The level of resting motor threshold in healthy aged showed broad correlations with both clinical manifestations and brain circuits related to left M1, which was absent in disease states. Besides, ICF exhibited distinct correlations with functional connections between right M1 and left middle temporal gyrus in all groups. The present study identified subtle differences in the functioning of PD and MSA related to bilateral M1. By combining clinical information, cortical excitability, and neuroimaging intuitively, we attempt to bring light on the potential mechanisms that may underlie the development of neurodegenerative disease.


Assuntos
Atrofia de Múltiplos Sistemas , Doença de Parkinson , Humanos , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Atrofia de Múltiplos Sistemas/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Idoso , Imageamento por Ressonância Magnética/métodos , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiopatologia , Eletromiografia , Neuroimagem/métodos
2.
J Neurochem ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994800

RESUMO

Oxidative stress is one of the major culprits causing dopaminergic neuron loss in Parkinson's disease (PD). DJ-1 is a protein with multiple actions against oxidative stress, apoptosis, neuroinflammation, etc. DJ-1 expression is decreased in sporadic PD, therefore increasing DJ-1 expression might be beneficial in PD treatment. However, drugs known to upregulate DJ-1 are still lacking. In this study, we identified a novel DJ-1-elevating compound called ChemJ through luciferase assay-based high-throughput compound screening in SH-SY5Y cells and confirmed that ChemJ upregulated DJ-1 in SH-SY5Y cell line and primary cortical neurons. DJ-1 upregulation by ChemJ alleviated MPP+-induced oxidative stress. In exploring the underlying mechanisms, we found that the transcription factor CREB1 bound to DJ-1 promoter and positively regulated its expression under both unstressed and 1-methyl-4-phenylpyridinium-induced oxidative stress conditions and that ChemJ promoted DJ-1 expression via activating PKA/CREB1 pathway in SH-SY5Y cells. Our results demonstrated that ChemJ alleviated the MPP+-induced oxidative stress through a PKA/CREB1-mediated regulation of DJ-1 expression, thus offering a novel and promising avenue for PD treatment.

3.
J Neurol Neurosurg Psychiatry ; 95(3): 222-228, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-37875337

RESUMO

BACKGROUND: Tai Chi has shown beneficial effects on the motor and non-motor symptoms of Parkinson's disease (PD), but no study has reported the effect of long-term Tai Chi training. OBJECTIVE: To examine whether long-term Tai Chi training can maintain improvement in patients with PD. METHODS: Cohorts of patients with PD with Tai Chi training (n=143) and patients with PD without exercise as a control group (n=187) were built from January 2016. All subjects were assessed at baseline and in November 2019, October 2020 and June 2021. A logarithmic linear model was used to analyse rating scales for motor and non-motor symptoms. The need to increase antiparkinsonian therapies was presented as a Kaplan-Meier plot and as a box plot. The bootstrap method was used to resample for statistical estimation. RESULTS: Tai Chi training reduced the annual changes in the deterioration of the Unified Parkinson's Disease Rating Scale and delayed the need for increasing antiparkinsonian therapies. The annual increase in the levodopa equivalent daily dosage was significantly lower in the Tai Chi group. Moreover, patients benefited from Tai Chi training in motor symptoms, non-motor symptoms and complications. CONCLUSION: Tai Chi training has a long-term beneficial effect on PD, with an improvement in motor and non-motor symptoms and reduced complications. TRIAL REGISTRATION NUMBER: NCT05447975.


Assuntos
Doença de Parkinson , Tai Chi Chuan , Humanos , Tai Chi Chuan/métodos , Seguimentos , Doença de Parkinson/terapia , Terapia por Exercício/métodos , Antiparkinsonianos , Qualidade de Vida
4.
Mov Disord ; 39(8): 1397-1402, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38561921

RESUMO

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathies. Fecal short-chain fatty acid (SCFA) changes in iRBD and the relationships with synucleinopathies have never been investigated. OBJECTIVES: To investigate fecal SCFA changes among iRBD, multiple system atrophy (MSA), and Parkinson's disease (PD), and evaluate their relationships. METHODS: Fecal SCFAs and gut microbiota were measured in 29 iRBD, 42 MSA, 40 PD, and 35 normal controls (NC) using gas chromatography-mass spectrometry and 16S rRNA gene sequencing. RESULTS: Compared with NC, fecal SCFA levels (propionic, acetic, and butyric acid) were lower in iRBD, MSA, and PD. Combinations of these SCFAs could differentiate NC from iRBD (AUC 0.809), MSA (AUC 0.794), and PD (AUC 0.701). Decreased fecal SCFAs were associated with the common reducing SCFA-producing gut microbiota in iRBD, MSA, and PD. CONCLUSIONS: iRBD shares similar fecal SCFA alterations with MSA and PD, and the combination of these SCFAs might be a potential synucleinopathies-related biomarker. © 2024 International Parkinson and Movement Disorder Society.


Assuntos
Ácidos Graxos Voláteis , Fezes , Microbioma Gastrointestinal , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Atrofia de Múltiplos Sistemas/metabolismo , Transtorno do Comportamento do Sono REM/metabolismo , Doença de Parkinson/metabolismo , Fezes/química , Fezes/microbiologia , Masculino , Feminino , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/análise , Idoso , Pessoa de Meia-Idade , Microbioma Gastrointestinal/fisiologia
5.
J Org Chem ; 89(7): 4438-4443, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38471105

RESUMO

A straight and efficient protocol for the synthesis of hindered indole-ethers via C-H alkoxylation of indoles was developed by a cobalt-catalyzed cross-dehydrogenative coupling reaction with secondary alcohols. The selection of the salicylaldehyde-Co(II) catalyst enables the reaction to proceed under conditions without acid or base addition in the presence of limited alcohols. The protocol has broad substrate scope for both indole and secondary alcohols and exhibits good functional tolerance. The synthetic applications are proven by gram-scale reaction and further diversification of the product. Preliminary mechanistic investigations indicate that the activation of C-H bonds is not the rate-determining step of the reaction.

6.
BMC Neurol ; 23(1): 362, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37803250

RESUMO

BACKGROUND: Parkinson's disease (PD) is often clinically associated with posture instability and more easily falling. The Berg balance scale is a clinical indicator commonly used to subjectively evaluate a patient's balance ability. Meanwhile, computerized force platforms have been used in research on postural control. The various parameters obtained from posturography are interpreted to assess balance ability. The present study aims to explore the correlations between posturographic variables and the BBS, and furthermore to efficiently evaluate postural instability and fall risk of early and moderate PD patients. METHODS: A total of 46 PD patients were involved in the experiment. Patients were asked to perform BBS tests and force platform tests under eye open (EO) and eye closed (EC) conditions. The recorded COP signal was analyzed with the time domain statistical method, the frequency domain method of Power Spectral Density (PSD), and structural methods of Stabilogram Diffusion Analysis (SDA), Sway Density Plot (SDP) to retrieve different posturographic variables. The correlation between posturographic variables under EO and EC conditions with BBS was compared statistically. The significantly correlated posturographic parameters were then applied to analyze posturographic differences between different groups: faller vs. non-faller (patients with/without a history of falls in the past 12 months). RESULTS: Among the different posturographic parameters, the prediction ellipse area, the slope of the regression line at a high-frequency band of PSD in the medial-lateral (ML) direction, the crossover point of the regression lines of SDA in the anterior-posterior (AP) direction, and the distance between successive peaks of SDP had significant correlations with BBS. These selected BBS-related parameters also showed significant differences between faller and non-faller. The selected posturographic parameters can be used as effective indicators to evaluate the balance ability of Parkinson's disease patients.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Equilíbrio Postural
7.
J Neuroinflammation ; 19(1): 215, 2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36058959

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disease and the most common cause of dementia. Among various pathophysiological aspects, microglia are considered to play important roles in the pathogenesis of AD. Genome wide association studies (GWAS) showed that the majority of AD risk genes are highly or exclusively expressed in microglia, underscoring the critical roles of microglia in AD pathogenesis. Recently, omics technologies have greatly advanced our knowledge of microglia biology in AD. Omics approaches, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics/lipidomics, present remarkable opportunities to delineate the underlying mechanisms, discover novel diagnostic biomarkers, monitor disease progression, and shape therapeutic strategies for diseases. In this review, we summarized research based on microglial "omics" analysis in AD, especially the recent research advances in the identification of AD-associated microglial subsets. This review reinforces the important role of microglia in AD and advances our understanding of the mechanism of microglia in AD pathogenesis. Moreover, we proposed the value of microglia-based omics in the development of therapeutic strategies and biomarkers for AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Biomarcadores , Estudo de Associação Genômica Ampla , Humanos , Microglia/patologia , Doenças Neurodegenerativas/patologia
8.
J Sep Sci ; 44(8): 1706-1715, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33624922

RESUMO

A moisture-sensitive metal-organic framework CoII (pybz)2 ·2DMF was synthesized and applied as the adsorbent of dispersive solid-phase extraction. The structure changed after water treatment due to the fact that two chelate carboxylate groups on the skeleton were transformed to monodentate because of the coordination of water molecules. The material showed good adsorption for fluorene, phenanthrene, fluoranthene, and pyrene in water because of the π-π conjugation and π-complexation effects. Coupled with high-performance liquid chromatography, a dispersive solid-phase extraction method of determining the content of fluorene, phenanthrene, fluoranthene, and pyrene in apple samples was established after optimizing the extraction conditions. Methanol containing 4% acetic acid was used as the effective eluent. The linearities were 0.5-1000 µg/kg for fluorene, phenanthrene and 5-1000 µg/kg for fluoranthene, pyrene. The limits of detection were 0.06-0.6 µg/kg, and the recoveries were 94.4-116.4%. The method has a high sensitivity for the determination of four polycyclic aromatic hydrocarbons in apple samples.


Assuntos
Benzoatos/química , Cobalto/química , Estruturas Metalorgânicas/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Extração em Fase Sólida , Cromatografia Líquida de Alta Pressão
9.
BMC Neurol ; 20(1): 114, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228519

RESUMO

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare movement disorder with poor prognosis. This retrospective study aimed to characterize the natural history of PSP and to find predictors of shorter survival and faster decline of activity of daily living. METHOD: All patients recruited fulfilled the movement disorder society (MDS) clinical diagnostic criteria for PSP (MDS-PSP criteria) for probable and possible PSP with median 12 years. Data were obtained including age, sex, date of onset, age at onset (AAO), symptoms reported at first visit and follow-up, date of death and date of institutionalization. Magnetic resonance imaging was collected at the first visit. Endpoints were death and institutionalization. Kaplan-Meier method and Cox proportional hazard model were used to explore factors associated with early death and institutionalization. RESULTS: Fifty-nine patients fulfilling MDS-PSP criteria were enrolled in our study. Nineteen patients (32.2%) had died and 31 patients (52.5%) were institutionalized by the end of the follow-up. Predictors associated with poorer survival were late-onset PSP and decreased M/P area ratio. Predictors associated with earlier institutionalization were older AAO and decreased M/P area ratio. CONCLUSION: Older AAO and decreased M/P area ratio were predictors for earlier dearth and institutionalization in PSP. The neuroimaging biomarker M/P area ratio was a predictor for prognosis in PSP.


Assuntos
Progressão da Doença , Mesencéfalo/patologia , Ponte/patologia , Paralisia Supranuclear Progressiva/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Paralisia Supranuclear Progressiva/diagnóstico
10.
Surg Endosc ; 34(12): 5274-5282, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31834511

RESUMO

BACKGROUND: Transoral endoscopic thyroid surgery via the vestibular approach (TOETVA) has been gradually accepted worldwide due to its scar-free effect on the neck. Even central cervical lymphadenectomy has been performed in some cases of papillary thyroid carcinoma (PTC). However, there are few reports involving lateral neck dissection with TOETVA. In this study, we attempted to perform selective lateral neck dissection (SLND) for PTC via a transoral vestibular approach. METHODS: This prospective study was conducted from January 2016 to December 2018 in twenty PTC patients with unilateral T1 tumors without capsular invasion and patients with abnormal level III and IV lymph nodes who underwent SLND via a transoral vestibular approach. RESULTS: Endoscopic surgery was successfully accomplished in all 20 PTC patients. The mean age was 29.2 ± 5.5 (20-41) years. The mean operation time was 146.0 ± 18.7 (114-193) min. The average postoperative hospital stay was 6.8 ± 1.3 (5-10) days. The mean number of removed nodes was 7.4 ± 2.5 (4-12) in the central neck and 10.9 ± 2.8 (6-16) in the lateral neck, and the positive yield amounts were 2.0 ± 1.2 (0-4) and 2.7 ± 1.9 (0-6), respectively. No major complications occurred except for 1 case of transient unilateral recurrent laryngeal nerve palsy and two cases of effusion in the operative area. No evidence of persistent or recurrent disease was observed in these patients during a mean follow-up of 24.3 ± 9.1 (6-36) months. The cosmetic results and protection of personal privacy of this procedure were excellent. CONCLUSION: Endoscopic SLND via the transoral vestibular approach is feasible, safe, and effective for selected PTCs. A multicenter large comparative study is necessary.


Assuntos
Endoscopia/métodos , Esvaziamento Cervical/métodos , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Adulto Jovem
11.
BMC Neurol ; 18(1): 122, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30134845

RESUMO

BACKGROUND: Chinese guidelines for management of Parkinson's disease (PD) have been issued and updated regularly since 2006. We undertook a cross-sectional survey to evaluate the impact of the latest edition (2014) on current approaches to the management of PD based on previous pilot works. METHODS: Seven hundred and seventeen participants, divided into 3 groups (GPs, Neurologists, and Specialists), recruited from 138 randomly chosen hospitals from 30 cities across China, participated by completing the questionnaire describing their current approaches before and after the guidelines were issued. RESULTS: Considerable discrepancies in management were apparent across the three categories, with different selection of first-choice medication for PD patients. There were also variations in management of concurrent psychiatric symptoms and dementia. Notably, over 50% of participants reported improvements in PD recognition and management by following the guidelines. CONCLUSIONS: The increasing use of Chinese clinical practice guidelines for PD management is having a positive impact on the optimization of care, which in turn offers important economic benefits.


Assuntos
Hospitais/estatística & dados numéricos , Doença de Parkinson , Padrões de Prática Médica/estatística & dados numéricos , China/epidemiologia , Estudos Transversais , Humanos , Neurologistas/estatística & dados numéricos , Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , Médicos/estatística & dados numéricos , Inquéritos e Questionários
12.
Mov Disord ; 32(7): 1047-1055, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28712121

RESUMO

BACKGROUND AND OBJECTIVES: Asymmetric onset of motor symptoms in PD can affect cognitive function. We examined whether motor-symptom laterality could affect feedback-based associative learning and explored its underlying neural mechanism by functional magnetic resonance imaging in PD patients. METHODS: We recruited 63 early-stage medication-naïve PD patients (29 left-onset medication-naïve patients, 34 right-onset medication-naïve patients) and 38 matched normal controls. Subjects completed an acquired equivalence task (including acquisition, retention, and generalization) and resting-state functional magnetic resonance imaging scans. Learning accuracy and response time in each phase of the task were recorded for behavioral measures. Regional homogeneity was used to analyze resting-state functional magnetic resonance imaging data, with regional homogeneity lateralization to evaluate hemispheric functional asymmetry in the striatum. RESULTS: Left-onset patients made significantly more errors in acquisition (feedback-based associative learning) than right-onset patients and normal controls, whereas right-onset patients performed as well as normal controls. There was no significant difference among these three groups in the accuracy of either retention or generalization phase. The three groups did not show significant differences in response time. In the left-onset group, there was an inverse relationship between acquisition errors and regional homogeneity in the right dorsal rostral putamen. There were no significant regional homogeneity changes in either the left or the right dorsal rostral putamen in right-onset patients when compared to controls. CONCLUSIONS: Motor-symptom laterality could affect feedback-based associative learning in PD, with left-onset medication-naïve patients being selectively impaired. Dysfunction in the right dorsal rostral putamen may underlie the observed deficit in associative learning in patients with left-sided onset.© 2016 International Parkinson and Movement Disorder Society.


Assuntos
Aprendizagem por Associação/fisiologia , Disfunção Cognitiva/fisiopatologia , Lateralidade Funcional/fisiologia , Neuroimagem Funcional/métodos , Doença de Parkinson/fisiopatologia , Putamen/fisiopatologia , Idoso , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Retroalimentação Psicológica/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Putamen/diagnóstico por imagem
13.
Arch Gynecol Obstet ; 295(3): 721-729, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28035488

RESUMO

BACKGROUND: Epidemiological studies assessing the relationship between dietary vitamin B2 and the risk of breast cancer have produced inconsistent results. Thus, we conducted this meta-analysis of epidemiologic studies to evaluate this association. METHODS: We searched English-language MEDLINE publications and conducted a manual search to screen eligible articles. A random-effect model was used to pool study-specific risk estimates. Egger's linear regression test was also used to detect publication bias in meta-analysis. RESULTS: In our meta-analysis, ten studies comprising totally 12,268 breast cancer patients were available in the analyses. Pooled relative risk (RR) comparing the highest to the lowest vitamin B2 intake and breast cancer incidence was 0.85 [95% confidence interval (CI) = 0.76-0.95]. No significant heterogeneity existed across the studies (P = 0.086, I 2 = 40.7%). No publication bias was found. The results of dose-response analysis also showed that an increment of 1 mg/day was inversely related to the risk of breast cancer (RR = 0.94; 95% CI = 0.90-0.99). CONCLUSIONS: Results from our meta-analysis indicated that dietary vitamin B2 intake is weakly related to the reduced risk of breast cancer. Additional research is also necessary to further explore this association.


Assuntos
Neoplasias da Mama/prevenção & controle , Riboflavina/administração & dosagem , Neoplasias da Mama/etiologia , Suplementos Nutricionais , Feminino , Humanos , Risco
15.
Mol Cell Biochem ; 399(1-2): 7-15, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25280398

RESUMO

As a cholesterol-induced metabolic disease, cholesterolosis of the gallbladder is often resected clinically, which could lead to many complications. The histopathology of cholesterolosis is due to excessive lipid droplet accumulation in epithelial and subcutaneous tissues. The main components of lipid droplets are cholesterol esters (CEs). Removal of CEs from gallbladder epithelial cells (GBECs) is very important for maintaining intracellular cholesterol homeostasis and for treating cholesterol-related diseases. In this study, pioglitazone was used to reduce intracellular CEs. To further elucidate the mechanism, cholesterolosis GBECs were treated with pioglitazone, 22-(R)-hydroxycholesterol (a liver X receptor α (LXRα) agonist), or peroxisome proliferator-activated receptor gamma (PPARγ) siRNA. Western blotting for PPARγ, LXRα, ATP-binding cassette transporter A1 (ABCA1), and neutral cholesteryl ester hydrolase 1 (NCEH1) was performed. At length, cholesterol efflux to apoA-I was measured, and oil red O staining was used to visualize lipid droplet variations in cells. In conclusion, we observed that pioglitazone increased ABCA1 expression in an LXR-dependent manner and NCEH1 expression in an LXRα-independent manner, which mobilized CE hydrolysis and cholesterol efflux to reduce lipid droplet content in cholesterolosis GBECs. Our data provide a plausible alternative to human gallbladder cholesterolosis.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Doenças da Vesícula Biliar/tratamento farmacológico , Gotículas Lipídicas/efeitos dos fármacos , Transtornos do Metabolismo dos Lipídeos/tratamento farmacológico , Tiazolidinedionas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Vesícula Biliar/efeitos dos fármacos , Vesícula Biliar/metabolismo , Humanos , Receptores X do Fígado , Receptores Nucleares Órfãos/metabolismo , PPAR gama/metabolismo , Pioglitazona , Esterol Esterase , Ativação Transcricional/efeitos dos fármacos
16.
Can J Neurol Sci ; 42(4): 242-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26153040

RESUMO

INTRODUCTION: The mortality of Parkinson's disease (PD) and its associated risk factors among clinically definite PD patients in China has been rarely investigated. Our study aimed to identify the mortality rates and predictors of death in PD patients in China. METHODS: 157 consecutive, clinically definite PD patients from the urban area of Shanghai were recruited from a central hospital based movement disorder clinic in 2006. All patients were regularly followed up at the clinic until December 31, 2011, or death. Mortality and associations with baseline demographics, health and medical factors were then determined within the cohort. RESULTS: After 5 years, 11(7%) patients had died. The standardised mortality ratio was 0.62 (95% CI 0.32 to 1.07, P=0.104). The main causes of death were pneumonia (54.5%, 6/11) and digestive disorders (18.2%, 2/11), respectively. Age at onset, independent living, the mini mental state examination score, the Parkinson's disease sleep scale score and the Epworth sleepiness scale score at baseline were statistically significantly different between the survival group and the deceased group (P<0.05). Across all participants, risk factors for death included low mini mental state examination score, and high Epworth sleepiness scale score according to a binary variable logistic regression analysis. CONCLUSIONS: This study confirms the similar survival of patients with PD to the control population up to a follow-up of 5 years. Interventions tailored to potential risk factors associated with death may offer further benefits.


Assuntos
Doença de Parkinson/mortalidade , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , China/epidemiologia , Estudos de Coortes , Doenças do Sistema Digestório/etiologia , Doenças do Sistema Digestório/mortalidade , Feminino , Seguimentos , Nível de Saúde , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Pneumonia/etiologia , Pneumonia/mortalidade , Fatores de Risco , Sono , Fatores Socioeconômicos , Análise de Sobrevida , População Urbana
17.
Biochem Biophys Res Commun ; 447(1): 152-7, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24704452

RESUMO

Cholesterosis is a disease of cholesterol metabolism characterized by the presence of excessive lipid droplets in the cytoplasm. These lipid droplets are mainly composed of cholesterol esters derived from free cholesterol. The removal of excess cholesterol from gallbladder epithelial cells (GBECs) is very important for the maintenance of intracellular cholesterol homeostasis and the preservation of gallbladder function. Several lines of evidence have indicated that the activation of either peroxisome proliferator-activated receptor gamma (PPARγ) or liver X receptor α (LXRα) relates to cholesterol efflux. While pioglitazone can regulate the activation of PPARγ, 22(R)-hydroxycholesterol can activate LXRα and is a metabolic intermediate in the biosynthesis of steroid hormones. However, the effect of 22(R)-hydroxycholesterol in combination with pioglitazone on cholesterosis of the gallbladder is unclear. GBECs were treated with pioglitazone, 22(R)-hydroxycholesterol or PPARγ siRNA followed by Western blot analysis for ATP-binding cassette transporter A1 (ABCA1), PPARγ and LXRα. Cholesterol efflux to apoA-I was determined, and Oil Red O staining was performed to monitor variations in lipid levels in treated GBECs. Our data showed that 22(R)-hydroxycholesterol can modestly up-regulate LXRα while simultaneously increasing ABCA1 by 56%. The combination of 22(R)-hydroxycholesterol and pioglitazone resulted in a 3.64-fold increase in ABCA1 expression and a high rate of cholesterol efflux. Oil Red O staining showed an obvious reduction in the lipid droplets associated with cholesterosis in GBECs. In conclusion, the present findings indicate that the anti-lipid deposition action of 22(R)-hydroxycholesterol combined with pioglitazone involves the activation of the PPARγ-LXRα-ABCA1 pathway, increased ABCA1 expression and the efflux of cholesterol from GBECs. Thus, 22(R)-hydroxycholesterol synergistically combined with pioglitazone to produce a remarkable effect on lipid deposition in cholesterosis GBECs.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/fisiologia , Ésteres do Colesterol/metabolismo , Doenças da Vesícula Biliar/tratamento farmacológico , Hidroxicolesteróis/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Receptores Nucleares Órfãos/fisiologia , PPAR gama/fisiologia , Tiazolidinedionas/uso terapêutico , Células Cultivadas , Sinergismo Farmacológico , Células Epiteliais/metabolismo , Vesícula Biliar/citologia , Humanos , Receptores X do Fígado , Pioglitazona
18.
Heliyon ; 10(13): e33616, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39050460

RESUMO

Colorectal cancer (CRC) is a prevalent and aggressive malignancy characterized by a complex tumor microenvironment (TME). Given the variations in the level of adipocyte infiltration in TME, the prognosis may differ among CRC patients. Thus, there is an urgent need to establish a reliable method for identifying adipocyte subtypes in CRC in order to elucidate the impact of adipocyte infiltration on CRC treatment and prognosis. Herein, 144 adipocyte-infiltration-related genes (AIRGs) were identified as predictive markers for the immune-associated features and prognosis of CRC patients. Based on the 144 genes, the unsupervised clustering algorithm identified two distinct clusters of CRC patients with variations in molecular and signaling pathways, clinicopathological characteristics and responses to CRC chemotherapy and immunotherapy. Furthermore, an AIRG prognostic signature was constructed and validated in independent datasets. Overall, this study developed a prognostic signature based on AIRGs in CRC, which may contribute to the development of personalized treatment strategies and enhance prognostic prediction for CRC patients.

19.
NPJ Digit Med ; 7(1): 169, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926552

RESUMO

Gait impairments are among the most common and disabling symptoms of Parkinson's disease and worsen as the disease progresses. Early detection and diagnosis of subtype-specific gait deficits, as well as progression monitoring, can help to implement effective and preventive personalized treatment for PD patients. Yet, the gait features have not been fully studied in PD and its motor subtypes. To characterize comprehensive and objective gait alterations and to identify the potential gait biomarkers for early diagnosis, subtype differentiation, and disease severity monitoring. We analyzed gait parameters related to upper/lower limbs, trunk and lumbar, and postural transitions from 24 tremor-dominant (TD) and 20 postural instability gait difficulty (PIGD) dominant PD patients who were in early stage and 39 matched healthy controls (HC) during the Timed Up and Go test using wearable sensors. Results show: (1) Both TD and PIGD groups showed restricted backswing range in bilateral lower extremities and more affected side (MAS) arm, reduced trunk and lumbar rotation range in the coronal plane, and low turning efficiency. The receiver operating characteristic (ROC) analysis revealed these objective gait features had high discriminative value in distinguishing both PD subtypes from the HC with the area under the curve (AUC) values of 0.7~0.9 (p < 0.01). (2) Subtle but measurable gait differences existed between TD and PIGD patients before the onset of clinically apparent gait impairment. (3) Specific gait parameters were significantly associated with disease severity in TD and PIGD subtypes. Objective gait biomarkers based on wearable sensors may facilitate timely and personalized gait treatments in PD subtypes through early diagnosis, subtype differentiation, and disease severity monitoring.

20.
Sci Rep ; 14(1): 5517, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448514

RESUMO

Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease. UC confronts with severe challenges including the unclear pathogenesis and lack of specific diagnostic markers, demanding for identifying predictive biomarkers for UC diagnosis and treatment. We perform immune infiltration and weighted gene co-expression network analysis on gene expression profiles of active UC, inactive UC, and normal controls to identify UC related immune cell and hub genes. Neutrophils, M1 macrophages, activated dendritic cells, and activated mast cells are significantly enriched in active UC. MMP-9, CHI3L1, CXCL9, CXCL10, CXCR2 and S100A9 are identified as hub genes in active UC. Specifically, S100A9 is significantly overexpressed in mice with colitis. The receiver operating characteristic curve demonstrates the excellent performance of S100A9 expression in diagnosing active UC. Inhibition of S100A9 expression reduces DSS-induced colonic inflammation. These identified biomarkers associated with activity in UC patients enlighten the new insights of UC diagnosis and treatment.


Assuntos
Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Calgranulina B/genética , Biologia Computacional , Biomarcadores
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