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EBioMedicine ; 74: 103732, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34864363


BACKGROUND: The survival time of amyotrophic lateral sclerosis (ALS) is greatly variable and protective or risk effects of the potential survival predictors are controversial. Thus, we aim to undertake a comprehensive meta-analysis of studies investigating non-genetic prognostic and survival factors in patients with ALS. METHODS: A search of relevant literature from PubMed, Embase, Cochrane library and other citations from 1st January 1966 to 1st December 020 was conducted. Random-effects models were conducted to pool the multivariable or adjusted hazard ratios (HR) by Stata MP 16.0. PROSPERO registration number: CRD42021256923. FINDINGS: A total of 5717 reports were identified, with 115 studies meeting pre-designed inclusion criteria involving 55,169 ALS patients. Five dimensions, including demographic, environmental or lifestyle, clinical manifestations, biochemical index, therapeutic factors or comorbidities were investigated. Twenty-five prediction factors, including twenty non-intervenable and five intervenable factors, were associated with ALS survival. Among them, NFL (HR:3.70, 6.80, in serum and CSF, respectively), FTD (HR:2.98), ALSFRS-R change (HR:2.37), respiratory subtype (HR:2.20), executive dysfunction (HR:2.10) and age of onset (HR:1.03) were superior predictors for poor prognosis, but pLMN or pUMN (HR:0.32), baseline ALSFRS-R score (HR:0.95), duration (HR:0.96), diagnostic delay (HR:0.97) were superior predictors for a good prognosis. Our results did not support the involvement of gender, education level, diabetes, hypertension, NIV, gastrostomy, and statins in ALS survival. INTERPRETATION: Our study provided a comprehensive and quantitative index for assessing the prognosis for ALS patients, and the identified non-intervenable or intervenable factors will facilitate the development of treatment strategies for ALS. FUNDING: This study was supported by the National Natural Science Fund of China (Grant No. 81971188), the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (Grant No. 2019HXFH046), and the Science and Technology Bureau Fund of Sichuan Province (No. 2019YFS0216).

Esclerose Amiotrófica Lateral/mortalidade , Feminino , Humanos , Estilo de Vida , Masculino , Prognóstico , Medição de Risco , Análise de Sobrevida , Adulto Jovem
Front Genet ; 12: 765833, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868249


Background: The association between inflammation and neurodegeneration has long been observed in parkinson's disease (PD) and multiple system atrophy (MSA). Previous genome-wide association studies (GWAS) and meta-analyses have identified several risk loci in inflammation-associated genes associated with PD. Objective: To investigate whether polymorphisms in some inflammation-associated genes could modulate the risk of developing PD and MSA in a Southwest Chinese population. Methods: A total of 2,706 Chinese subjects comprising 1340 PD, 483 MSA and 883 healthy controls were recruited in the study. Three polymorphisms (rs2074404 GG/GT/TT, rs17425622 CC/CT/TT, rs34043159 CC/CT/TT) in genes linked to inflammation in all the subjects were genotyped by using the Sequenom iPLEX Assay. Results: The allele G of WNT3 rs2074404 can increase risk on PD (OR: 1.048, 95% CI: 1.182-1.333, p = 0.006), exclusively in the LOPD subgroup (OR: 1.166, 95% CI:1.025-1.327, p = 0.019), but not in EOPD or MSA. And the recessive model analysis also demonstrated an increased PD risk in GG genotype of this locus (OR = 1.331, p = 0.007). However, no significant differences were observed in the genotype distributions and alleles of HLA-DRB5 rs17425622 and IL1R2 rs34043159 between the PD patients and controls, between the MSA patients and controls, or between subgroups of PD or MSA and controls. Conclusion: Our results suggested the allele G of WNT3 rs2074404 have an adverse effect on PD and particularly, on the LOPD subgroup among a Chinese population.

J Parkinsons Dis ; 11(4): 1845-1855, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34250953


BACKGROUND: Genetic studies have indicated that variants in several lysosomal genes are risk factors for idiopathic Parkinson's disease (PD). However, the role of lysosomal genes in PD in Asian populations is largely unknown. OBJECTIVE: This study aimed to analyze rare variants in lysosomal related genes in Chinese population with early-onset and familial PD. METHODS: In total, 1,136 participants, including 536 and 600 patients with sporadic early-onset PD (SEOPD) and familial PD, respectively, underwent whole-exome sequencing to assess the genetic etiology. Rare variants in PD were investigated in 67 candidate lysosomal related genes (LRGs), including 15 lysosomal function-related genes and 52 lysosomal storage disorder genes. RESULTS: Compared with the autosomal dominant PD (ADPD) or SEOPD cohorts, a much higher proportion of patients with multiple rare damaging variants of LRGs were found in the autosomal recessive PD (ARPD) cohort. At a gene level, rare damaging variants in GBA and MAN2B1 were enriched in PD, but in SCARB2, MCOLN1, LYST, VPS16, and VPS13C were much less in patients. At an allele level, GBA p. Leu483Pro was found to increase the risk of PD. Genotype-phenotype correlation showed no significance in the clinical features among patients carrying a discrepant number of rare variants in LRGs. CONCLUSION: Our study suggests rare variants in LRGs might be more important in the pathogenicity of ARPD cases compared with ADPD or SEOPD. We further confirm rare variants in GBA are involve in PD pathogenecity and other genes associated with PD identified in this study should be supported with more evidence.

Lisossomos , Doença de Parkinson , China , Estudos de Coortes , Estudos de Associação Genética , Humanos , Lisossomos/genética , Doença de Parkinson/genética
Sci Rep ; 10(1): 6777, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32303691


An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sci Rep ; 7(1): 7185, 2017 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-28775264


Magnesium oxide (MgO) sensing membranes in pH-sensitive electrolyte-insulator-semiconductor structures were fabricated on silicon substrate. To optimize the sensing capability of the membrane, CF4 plasma was incorporated to improve the material quality of MgO films. Multiple material analyses including FESEM, XRD, AFM, and SIMS indicate that plasma treatment might enhance the crystallization and increase the grain size. Therefore, the sensing behaviors in terms of sensitivity, linearity, hysteresis effects, and drift rates might be improved. MgO-based EIS membranes with CF4 plasma treatment show promise for future industrial biosensing applications.

Ai Zheng ; 21(4): 346-50, 2002 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-12452008


BACKGROUND & OBJECTIVE: Tubeimoside, which is composed of tubeimoside I (79%) and II (21%), was isolated from the tubers of Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), a traditional Chinese medicine, "Tu-Bei-Mu". This study was designed to investigate the anti-tumor mechanism of tubeimoside. METHODS: Growth inhibition was measured by MTT assay. Induction of cell cycle arrest and apoptosis was determined by flow cytometry, fluorescence and electron microscopy, and gel electrophoresis of fragmented DNA. RESULTS: Tubeimoside display strong growth inhibitory effect in a dose- and time-dependant manner against HeLa cells with estimated IC50 values of 20.0, 18.8, and 8.8 mumol/L after 24, 48, and 72 h of treatment with tubeimoside. The flow cytometry profiles revealed that treatment with tubeimoside (5 h; 15, 30, 35 mumol/L) led to a dose-dependant shift from 9.80% up to 21.90%, and 27.00% in percentage of cells with a G2/M-like DNA content. On the other hand, treatment with tubeimoside (12 h, 15, 30, 35 mumol/L) led to a time-dependant shift from 8.20% up to 21.40%, 31.15%, and 34.55%, respectively. Exposure of HeLa cells to 40 mumol/L of tubeimoside induced nuclear shrinkage, chromation condensation and margination against nuclear envelope, subdiploid peak, and DNA fragmentation, characteristic as seen in apoptotic cells. CONCLUSION: Induction of cell cycle arrest and apoptosis may play an important role in the anti-tumor effect of tubeimoside.

Antineoplásicos/farmacologia , Apoptose , Saponinas/farmacologia , Triterpenos/farmacologia , Ciclo Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células HeLa , Humanos