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1.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

2.
Mol Neurobiol ; 58(7): 3435-3442, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33723766

RESUMO

Functional and genetic studies have identified association between several Zinc finger (ZNF) proteins and Parkinson's disease (PD). However, most of them were still awaiting further replications, especially in the Asian population. Here, we systematically selected PD-relevant ZNF genes and analyzed the genetic associations between these ZNFs and PD in a large Chinese PD cohort. We identified rare variants (minor allele frequency < 0.01) in 743 unrelated patients with early-onset PD (EOPD, age at onset < 50 years) using whole exome sequencing and evaluated the association between rare variants and EOPD at both allele and gene levels. Totally 91 rare variants were identified in ZNF746, ZNF646, ZNF184, ZNF165, ZND219, and GLIS1. One variant p.R373H in ZNF219 and two variants p.G161D and p.R158H in ZNF746 were significantly associated with EOPD, and gene-based burden analysis showed enrichment of rare variants of ZNF746 in EOPD. Our findings build up the connection between ZNF746 and PD from a genetic perspective for the first time, supplement current understanding for the genetic role of ZNFs in EOPD, and broaden the mutation spectrum in PD.

3.
J Med Chem ; 64(6): 3131-3152, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33715360

RESUMO

Uveal melanoma is the ocular malignancy and mainly driven by oncogenic mutations of Gαq/11 proteins. Previous targeted therapy for melanoma treatment was limited to specific downstream signaling pathway, and inhibiting the "molecular switches" G proteins for melanoma treatment therapy was rarely described. We herein report the discovery of imidazopiperazine derivatives as Gαq/11 protein inhibitors. The most promising compound GQ127 showed good efficacy and safety in inositol monophosphate (IP1) assay by directly inhibiting Gαq/11 proteins. GQ127 induced uveal melanoma cells apoptosis and displayed potent antitumor activities in uveal melanoma cells viability, migration, and invasion. The effects of GQ127 on Gαq/11 signaling pathway were confirmed by analyzing the downstream effectors yes-associated protein (YAP) and extracellular signal-regulated kinase (ERK). More importantly, GQ127 significantly suppressed UM xenograft growth in mouse model without severe toxicity at the testing dose. These findings provide a lead compound that directly targets the Gαq/11 proteins for uveal melanoma treatment.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/antagonistas & inibidores , Melanoma/tratamento farmacológico , Piperazina/química , Piperazina/farmacologia , Neoplasias Uveais/tratamento farmacológico , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Melanoma/metabolismo , Piperazina/síntese química , Neoplasias Uveais/metabolismo
4.
Acta Pharm Sin B ; 11(1): 13-29, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33532178

RESUMO

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.

5.
J Org Chem ; 86(2): 1667-1675, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33406829

RESUMO

We report the direct asymmetric synthesis of pyrimido[2,1-b]benzothiazoles using a commercially available chiral amine catalyst. A variety of 2-benzothiazolimines and aldehydes were well tolerated under the reaction conditions and generated the corresponding products in 81-99% yields with excellent diastereoselectivities and enantioselectivities (up to >20:1 dr, 99% ee). Furthermore, the products could be easily converted to other useful chiral building blocks.

6.
Neural Regen Res ; 16(3): 591-595, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32985493

RESUMO

Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis. In the present retrospective case-control study, we included 582 patients with amyotrophic lateral sclerosis and 582 age- and sex-matched healthy controls. All amyotrophic lateral sclerosis participants received treatment in the Department of Neurology, West China Hospital, China, between May 2008 and December 2018. Serum creatine kinase levels in patients with amyotrophic lateral sclerosis were significantly higher than those in healthy controls. Subgroup analysis revealed that serum creatine kinase levels in men were higher than those in women in both amyotrophic lateral sclerosis patients and healthy controls. Compared with patients with bulbar-onset amyotrophic lateral sclerosis, patients with limb-onset amyotrophic lateral sclerosis had higher creatine kinase levels. Spearman's correlation analysis revealed that serum creatine kinase levels were not correlated with body mass index, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, or progression rate. After adjusting for prognostic covariates, higher log creatine kinase values were correlated with higher overall survival in the amyotrophic lateral sclerosis patients. We also investigated the longitudinal changes in serum creatine kinase levels in 81 amyotrophic lateral sclerosis patients; serum creatine kinase levels were decreased at the second blood test, which was sampled at least 6 months after the first blood test. Together, our results suggest that serum creatine kinase levels can be used as an independent factor for predicting the prognosis of amyotrophic lateral sclerosis patients. This study received ethical approval from the Ethics Committee of West China Hospital, China (approval No. 2015(236)) on December 23, 2015.

7.
J Org Chem ; 85(15): 9661-9671, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32603113

RESUMO

The catalytic asymmetric Mannich-type reaction of 3-hydroxy/3-aminooxindoles with 2-aminoacrylates to afford oxindole-derived acyclic amino acid derivatives bearing vicinal tetrasubstituted stereocenters is reported. (DHQ)2PHAL (4g) and quinine-derived squaramide (4d) were identified as efficient catalysts. Transformations of the Mannich-type reaction products highlight the utility of this synthetic strategy.

8.
Org Lett ; 22(5): 1858-1862, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32083880

RESUMO

We report the first highly enantio- and diastereoselective three-component Povarov reaction between anilines and aldehydes catalyzed by a chiral amine catalyst. A wide variety of substituted tetrahydroquinolines were obtained with moderate to good yields and excellent enantioselectivity and diastereoselectivity (up to 99% ee and >95:5 dr) under the reaction conditions. Furthermore, the reaction intermediates could be efficiently converted to other valuable building blocks.

9.
Org Lett ; 22(2): 584-588, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31904969

RESUMO

We describe herein the first asymmetric total synthesis and biological evaluation of the natural PDE4 inhibitor toddacoumalone and its stereoisomers. The key step of the total synthesis is a formal asymmetric [4 + 2] cycloaddition reaction catalyzed by chiral secondary amine catalysts. A variety of pyranoquinolinones and 3-methylcrotonaldehyde are well tolerated under the optimized reaction conditions, which paved the way for further SAR studies. Further biological evaluation showed 1a' with the best PDE4 inhibitory activity (IC50 = 0.18 µM).


Assuntos
Produtos Biológicos/farmacologia , Cumarínicos/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Produtos Biológicos/síntese química , Produtos Biológicos/química , Cumarínicos/síntese química , Cumarínicos/química , Reação de Cicloadição , Humanos , Estrutura Molecular , Inibidores da Fosfodiesterase 4/síntese química , Inibidores da Fosfodiesterase 4/química , Estereoisomerismo
10.
Environ Pollut ; 247: 736-744, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30721864

RESUMO

The bioavailability of the metalloid arsenic (As) in paddy soil is controlled by microbial cycling of As and other elements such as iron (Fe) and sulfur (S), which are strongly influenced by water management in paddy fields. In this study, we evaluated how water management affects As bioavailability by growing rice plants in a geogenic As-contaminated soil. We determined As speciation in soil porewater and the diversity of the associated microbial community. Continuous flooding enhanced the release of Fe and As and increased arsenite (As(III)) and methylated As species concentrations in the rice grain compared with aerobic treatment. Total inorganic and organic As in the grain was 84% and 81% lower, respectively, in the aerobic treatment compared with the continuous flooding treatment. The amounts of Fe(III)-reducing bacteria (FeRB) increased in the flooded rhizosphere soil. The abundance of FeRB in the soil correlated with the dissolution of Fe and As. Among the As-transformation genes quantified, the aioA gene for As(III) oxidation and arsM gene for As(III) methylation were most abundant. The arsM copy number correlated positively with the levels of dsrB (dissimilatory (bi) sulfite reductase ß-subunit), suggesting that dissimilatory sulfate-reducing bacteria (SRB) may play an important role in dimethylarsenate (DMAs(V)) production in soil. Our results show that decreased populations of rhizosphere FeRB and SRB contributed to a lower bioavailability of As, and decreased production of methylated arsenicals under oxic conditions.


Assuntos
Arsênio/análise , Arsenicais/análise , Conservação dos Recursos Hídricos/métodos , Microbiota , Oryza/química , Microbiologia do Solo , Poluentes do Solo/toxicidade , Arsênio/toxicidade , Arsenitos , Bactérias/genética , Ácido Cacodílico , Monitoramento Ambiental , Poluição Ambiental , Compostos Férricos , Inundações , Ferro , Oxirredução , Estruturas Vegetais/química , Rizosfera , Solo , Poluentes do Solo/análise , Enxofre
11.
Exp Ther Med ; 15(6): 5461-5468, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29904425

RESUMO

The present study aimed to investigate risk factors for renal recurrence in patients with type IV lupus nephritis (LN). Univariate and multivariate analyses were conducted to using the Cox proportional hazard model and the Kaplan-Meier method. A total 244 patients were diagnosed with type IV LN; 100 (28.49%) relapsed and 144 (41.03%) recovered successfully. Kaplan-Meier method analysis indicated that patients with type IV LN affecting the digestive tract had high renal recurrence rates. Patients with hyperglobulinemia, positive anti-ribonucleoprotein and anti-Sjögren's syndrome type B (anti-SSB) antibodies, thrombus in the loop or non-inflammatory necrotizing vasculopathy also had a high recurrence rate. Furthermore, patients achieving partial remission had an increased recurrence rate compared with patients achieving complete remission. Patients undergoing maintenance treatment with glucocorticoids alone had a higher recurrence rate compared with patients who used alternative treatment schemes. Univariate and multivariate regression analyses by the Cox proportional hazard model determined that the effect of systemic lupus erythematosus in the gastrointestinal tract, increased serum globulin levels and positive anti-SSB antibody at onset were risk factors for the recurrence of LN type IV. The present study demonstrated that clinical risk factors of renal recurrence in patients with LN type IV include LN in the gastrointestinal tract, increased serum globulin levels, positive anti-SSB antibodies at onset and the use of glucocorticoid-only maintenance treatment.

12.
J Microbiol ; 56(7): 507-515, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29948827

RESUMO

Methane production by methanogens in wetland is recognized as a significant contributor to global warming. Spartina alterniflora (S. alterniflora), which is an invasion plant in China's wetland, was reported to have enormous effects on methane production. But studies on shifts in the methanogen community in response to S. alterniflora invasion at temporal and spatial scales in the initial invasion years are rare. Sediments derived from the invasive species S. alterniflora and the native species Phragmites australis (P. australis) in pairwise sites and an invasion chronosequence patch (4 years) were analyzed to investigate the abundance and community structure of methanogens using quantitative real-time PCR (qPCR) and Denaturing gradient gel electrophoresis (DGGE) cloning of the methyl-coenzyme M reductase A (mcrA) gene. For the pairwise sites, the abundance of methanogens in S. alterniflora soils was lower than that of P. australis soils. For the chronosequence patch, the abundance and diversity of methanogens was highest in the soil subjected to two years invasion, in which we detected some rare groups including Methanocellales and Methanococcales. These results indicated a priming effect at the initial invasion stages of S. alterniflora for microorganisms in the soil, which was also supported by the diverse root exudates. The shifts of methanogen communities after S. alterniflora invasion were due to changes in pH, salinity and sulfate. The results indicate that root exudates from S. alterniflora have a priming effect on methanogens in the initial years after invasion, and the predominate methylotrophic groups (Methanosarcinales) may adapt to the availability of diverse substrates and reflects the potential for high methane production after invasion by S. alterniflora.


Assuntos
Metano/metabolismo , Methanobacteriaceae/metabolismo , Consórcios Microbianos/fisiologia , Plantas , Microbiologia do Solo , Biomassa , Enzimas de Restrição do DNA/genética , Ecossistema , Concentração de Íons de Hidrogênio , Ilhas , Metano/biossíntese , Methanobacteriaceae/genética , Methanococcales/genética , Methanococcales/isolamento & purificação , Methanococcales/metabolismo , Consórcios Microbianos/genética , Raízes de Plantas/microbiologia , Salinidade , Análise Espaço-Temporal , Sulfatos/metabolismo , Áreas Alagadas
13.
Environ Sci Pollut Res Int ; 25(19): 19134-19142, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29725924

RESUMO

With the increasing occurrence of water eutrophication and blooms, earthy-musty odor problems caused by cyanobacteria have been more and more apparent. These problems have a serious impact on aquatic ecosystems and drinking water safety and become one of the priorities of the water environment researches and managements. In the present study, genes associated with 2-MIB synthesis in cyanobacteria were studied by systematic investigation on molecular characterization and quantity of 2-MIB-producing cyanobacteria in China. Our results founded that Pseudoanabaena is an important 2-MIB-producing phytoplankton and predominant in summer in Qingcaosha reservoir, and the copy number of mic and 2-MIB concentration have strongly positive correlation. We also demonstrated that abundance of mic in water was significant correlation with that in sediment. These results will help us to understand the main taxa of the odoriferous cyanobacteria in the water bodies in China, understand the genetic basis of the odor substances in the cyanobacteria. Rapid, reliable monitoring and ecological research methods for the production of odor cyanobacteria in water bodies can be established based on these results.


Assuntos
Cianobactérias/química , Água Potável/microbiologia , Fitoplâncton/química , Canfanos/análise , China , Cianobactérias/metabolismo , Água Potável/química , Ecossistema , Eutrofização , Odorantes/análise , Estações do Ano
14.
Autoimmunity ; 50(8): 476-480, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29239254

RESUMO

OBJECTIVE: This study aims to evaluate the role of FEN1 E160D mutation in lupus nephritis (LN) patients with cell apoptosis dysfunction. METHODS: (1) Cell apoptosis was detected from 50 paraffin samples obtained from renal biopsies of patients with Class IV LN by TUNEL method and the relationship of the systemic lupus erythematosus disease activity index 2000 (SLEDAI 2000) and renal tissue cell apoptotic index (AI) was discussed. (2) FEN1 gene 61563142-61563342 containing E160D were analysed by extracting genomic DNA from peripheral blood collected from the above 50 LN patients and 25 patients with nephrectomy caused by renal trauma. The difference between these two groups was statistically significant. RESULTS: Cell apoptosis was detected in all patients with LN, and correlation analysis results revealed a positive relationship between SLEDAI 2000 and AI (r = 0.39, p = .032). The FEN1 gene 61563142-61563342 fragment had site mutations at C/- (+61563189), A/T (+61563198), A/- (+61563204), G/T (+61563303), and T/C (+61563304). However, no statistical significance was found between LN patients detected with cell apoptosis and healthy individuals. CONCLUSIONS: This study revealed that cell apoptosis dysfunction plays a key role in the pathogenesis of LN, even though the difference in FEN1 gene 61563142-61563342 between LN patients and healthy individuals was not statistically significant. Larger sample size studies or genome-wide association studies are needed.


Assuntos
Alelos , Apoptose/genética , Endonucleases Flap/genética , Predisposição Genética para Doença , Nefrite Lúpica/genética , Biópsia , Fragmentação do DNA , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Humanos , Nefrite Lúpica/diagnóstico , Masculino
15.
J Genet ; 94(3): 435-44, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26440082

RESUMO

Five monosomic alien addition lines (MAALs) of Brassica rapa ssp. pekinensis - B. oleracea var. capitata were obtained by hybridization and backcrossing between B. rapa ssp. pekinensis (female parent) and B. oleracea var. capitata. The alien linkage groups were identified using 42 B. oleracea var. capitata linkage group-specific markers as B. oleracea linkage groups C2, C3, C6, C7 and C8. Based on the chromosomal karyotype of root tip cells, these five MAALs added individual chromosomes from B. oleracea var. capitata: chr 1 (the longest), chr 2 or 3, chr 5 (small locus of 25S rDNA), chr 7 (satellite-carrying) and chr 9 (the shortest). Five disomic alien addition lines were then generated by selfing their corresponding MAALs.


Assuntos
Brassica/genética , Cruzamento , Cromossomos de Plantas , Ligação Genética , Marcadores Genéticos , Hibridização in Situ Fluorescente , Cariotipagem , Metáfase/genética , Fenótipo , Pólen/genética , Sementes/genética
16.
PLoS One ; 9(7): e101136, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24988301

RESUMO

Recent genomic sequencing of the foxtail millet, an abiotic, stress-tolerant crop, has provided a great opportunity for novel gene discovery and functional analysis of this popularly-grown grass. However, few stress-mediated gene families have been studied. Aldehyde dehydrogenases (ALDHs) comprise a gene superfamily encoding NAD (P) +-dependent enzymes that play the role of "aldehyde scavengers", which indirectly detoxify cellular ROS and reduce the effect of lipid peroxidation meditated cellular toxicity under various environmental stresses. In the current paper, we identified a total of 20 ALDH genes in the foxtail millet genome using a homology search and a phylogenetic analysis and grouped them into ten distinct families based on their amino acid sequence identity. Furthermore, evolutionary analysis of foxtail millet reveals that both tandem and segmental duplication contributed significantly to the expansion of its ALDH genes. The exon-intron structures of members of the same family in foxtail millet or the orthologous genes in rice display highly diverse distributions of their exonic and intronic regions. Also, synteny analysis shows that the majority of foxtail millet and rice ALDH gene homologs exist in the syntenic blocks between the two, implying that these ALDH genes arose before the divergence of cereals. Semi-quantitative and real-time quantitative PCR data reveals that a few SiALDH genes are expressed in an organ-specific manner and that the expression of a number of foxtail millet ALDH genes, such as, SiALDH7B1, SiALDH12A1 and SiALDH18B2 are up-regulated by osmotic stress, cold, H2O2, and phytohormone abscisic acid (ABA). Furthermore, the transformation of SiALDH2B2, SiALDH10A2, SiALDH5F1, SiALDH22A1, and SiALDH3E2 into Escherichia coli (E.coli) was able to improve their salt tolerance. Taken together, our results show that genome-wide identification characteristics and expression analyses provide unique opportunities for assessing the functional roles of foxtail millet ALDH genes in stress responses.


Assuntos
Aldeído Desidrogenase/biossíntese , Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Família Multigênica/fisiologia , Proteínas de Plantas/biossíntese , Setaria (Planta)/enzimologia , Aldeído Desidrogenase/genética , Proteínas de Plantas/genética , Tolerância ao Sal/fisiologia , Setaria (Planta)/genética , Estresse Fisiológico/fisiologia
17.
Int J Nurs Stud ; 48(4): 419-28, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20696428

RESUMO

BACKGROUND: Research has indicated that sleep disorders reduce the quality of life of heart failure patients. OBJECTIVES: To investigate quality of sleep, and the impact of poor sleep on quality of life among elderly versus younger heart failure patients. DESIGN: A two-group, cross-sectional study. SETTING: A community teaching hospital in Taipei, Taiwan. PARTICIPANTS: Voluntarily self-enrolled heart failure patients who did not have sleep apnea or restless leg syndrome. METHODS: There were 126 elderly and 67 young participants filled out five questionnaires (1) demographic information and current health status; (2) the Chinese Pittsburgh Sleep Quality Index; (3) the Chinese Epworth Sleepiness Scale, and (4) the short form (SF)-36 Taiwanese version. The major statistical procedures applied in this study were t-test, analysis of variance, Pearson's correlation, and a stepwise multiple linear regression. A p-value of <0.05 was adopted as significant. RESULTS: The prevalence of insomnia was 44.4% for the elderly group and 31.4% for the younger group. The top three prevalence sleep-disturbing events were: nocturia, long sleep latency, and early wake-up. In the elderly group, nocturnal dyspnea and long sleep latency were significant determinants of the mental (R(2)=0.23) and physical components (R(2)=0.21) of quality of life. In the young group, nocturnal dyspnea was a significant determinant of the mental component of quality of life (R(2)=0.15), and early wake-up was a significant determinant of the physical component of quality of life (R(2)=0.15). CONCLUSION: The sleep disorder of heart failure patients is disease-specific rather than a matter of age. The prevalence of insomnia of young heart failure patients was higher than that of the healthy elderly. The major determinants of poor night sleep quality in the elderly group were dyspnea and long sleep latency, and in the younger group, these were dyspnea and early wake-up. Those also were significant determinants of quality of life of the heart failure patients. IMPLICATIONS FOR NURSING PRACTICE: Since the sleep-related predictors of quality of life were different in the elderly versus younger heart failure patients, to identify the insomnia factors individually and to provide guidance of appropriate usage of sleep medications and other methods to promote sleep should be considered.


Assuntos
Qualidade de Vida , Sono/fisiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e Questionários , Taiwan
18.
Cancer Nurs ; 33(6): 454-60, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20562619

RESUMO

BACKGROUND: Most patients experience fatigue during chemotherapy. Ignoring this fatigue can contribute to worsening overall health of patients and a slowed recovery process. OBJECTIVE: We investigated the effectiveness of a warm-water footbath on relieving fatigue and insomnia problems in patients undergoing chemotherapy. METHODS: This was a 2-group, longitudinal study design. Adults diagnosed with gynecologic cancer and receiving a 4-series platinum chemotherapy regimen were recruited and then followed up for 6 months. They completed fatigue and insomnia items on the 1st, 2nd, 4th, 7th, and 14th days after each scheduled chemotherapy. Participants in the experimental group soaked their feet in 41°C to 42°C warm water for 20 minutes every evening, starting from the eve of receiving the first chemotherapy, whereas participants in the comparison group did not do so. RESULTS: : There were 25 and 18 participants in the comparison and experimental groups, respectively, who completed the study. Participants in the experimental group reported a significant reduction in fatigue and improvement in sleep quality from the second session of chemotherapy and continued to improve during the study period. CONCLUSIONS: A warm-water footbath intervention resulted in reduced fatigue and insomnia symptoms for gynecologic cancer patients during chemotherapy. IMPLICATIONS FOR PRACTICE: A warm-water footbath is local moist heat application. It is noninvasive and easy to apply at home. The findings provide empirical support that a warm-water footbath relieves fatigue and insomnia problems of patients undergoing chemotherapy. It can be a nonpharmaceutical method to help patients overcome fatigue and sleep problems during chemotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Fadiga/terapia , Neoplasias dos Genitais Femininos/complicações , Temperatura Alta/uso terapêutico , Hidroterapia/métodos , Distúrbios do Início e da Manutenção do Sono/terapia , Adulto , Idoso , Análise de Variância , Banhos/métodos , Fadiga/induzido quimicamente , Feminino , , Neoplasias dos Genitais Femininos/tratamento farmacológico , Indicadores Básicos de Saúde , Humanos , Pessoa de Meia-Idade , Compostos de Platina/efeitos adversos , Estudos Prospectivos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Água , Adulto Jovem
19.
Neurochem Res ; 35(8): 1214-23, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20455020

RESUMO

To assess RNAi mediated inhibition of the expression of wt-DYT1 on H(2)O(2)-induced toxicity in NIH 3T3 cells and primary cortical neurons. To detect the function of wild-type Torsin A and the effect of SiRNA on the wt-DYT1 gene. The shRNA expression vector was constructed by ligating annealed complementary shRNA oligonucleotides into the down-stream of the human U6 promoter (PU6) of the RNAi-ready pSIREN-Shuttle vector. Then, the pSIREN-Shuttle-DYT1-shRNA cassette was ligated to Adeno-X Viral DNA to construct the recombinant adenoviral vector pAd-DYT1-shRNA. Cultured cerebral cortical neurons and NIH 3T3 cells were transfected with pAd-DYT1-shRNA and pSIREN-Shuttle-DYT1-shRNA. We evaluated NIH 3T3 cells and neurons in the presence of oxidative stress using a TUNEL assay under different conditions. The knockdown efficacy of the DYT1 was confirmed by real-time RT-PCR and Western Blot analysis. After exposure to H(2)O(2,) the quantity of NIH 3T3 cells transfected with pSIREN-Shuttle-DYT1-shRNA, which stained positively in the TUNEL assay, was significantly higher than the cells transfected with pSIREN-Shuttle-negative control-shRNA. (44.85 +/- 1.81% vs. 8.98 +/- 2.73%, t = 26.168). There were significantly more apoptotic neurons infected with pAd-DYT1-shRNA (45.63 +/- 7.53%) than neurons infected with pAd-X-negative control-shRNA (17.33 +/- 2.43%) (t = 9.816). The observed silencing of wild-type Torsin A expression by DYT1-shRNA was sequence-specific. RNAi-mediated inhibition of the expression of wild-type Torsin A increases apoptosis caused by oxidative stress. It is reasonable to consider that wild-type Torsin A has the capacity to protect cortical neurons against oxidative stress, and in the development of DYT1-delta GAG-dystonia the neuroprotective function of wild-type Torsin A may be compromised.


Assuntos
Apoptose , Chaperonas Moleculares/biossíntese , Neurônios/metabolismo , Estresse Oxidativo , Interferência de RNA , Adenoviridae/genética , Animais , Células Cultivadas , Córtex Cerebral/citologia , Técnicas de Silenciamento de Genes , Vetores Genéticos , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Chaperonas Moleculares/genética , Neurônios/citologia , Plasmídeos , RNA Interferente Pequeno/genética , Transfecção
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