Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
1.
J Med Biochem ; 43(2): 209-218, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38699690

RESUMO

Background: To evaluate the predictive value of sICAM-1 and sP-Selectins in the risk of death in a prospective cohort of adult acute respiratory distress syndrome (ARDS). Methods: Adult ARDS patients were included. Plasma sICAM-1, sP-Selectins, and inflammatory cytokines (TNF-α, IL-1b, IL-6, IL-8, and IL-17A) were detected in ARDS subjects. The correlation between different factors and the potential of sICAM-1 and sP-Selectins as endothelial markers to predict the risk of deathfrom ARDS was analyzed.

2.
Front Public Health ; 12: 1336065, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601505

RESUMO

Background: Work stress is considered as a risk factor for coronary heart disease, but its link with heart rate variability (HRV) among heart attack survivors is unknown yet. The aim of this study was to investigate associations between baseline work stress and the changes of HRV over one-year after onset of acute coronary syndrome (ACS). Methods: Hundred and twenty-two patients with regular paid work before their first ACS episode were recruited into this hospital-based longitudinal cohort study. During hospitalization (baseline), all patients underwent assessments of work stress by job strain (JS) and effort-reward imbalance (ERI) models, and were assigned into low or high groups; simultaneously, sociodemographic and clinical data, as well depression, anxiety, and job burnout, were collected. Patients were followed up 1, 6, and 12 months after discharge, with HRV measurements at baseline and each follow-up point. Generalized estimating equations were used to analyze the effects of baseline work stress on HRV over the following 1 year. Results: After adjusting for baseline characteristics and clinical data, anxiety, depression, and burnout scores, high JS was not associated with any HRV measures during follow-up (all p > 0.10), whereas high ERI was significantly related to slower recovery of 5 frequency domain HRV measures (TP, HF, LF, VLF, and ULF) (all p < 0.001), and marginally associated with one time domain measure (SDNN) (p = 0.069). When mutually adjusting for both work stress models, results of ERI remained nearly unchanged. Conclusion: Work stress in terms of ERI predicted lower HRV during the one-year period after ACS, especially frequency domain measures.


Assuntos
Síndrome Coronariana Aguda , Estresse Ocupacional , Humanos , Estudos Longitudinais , Frequência Cardíaca/fisiologia , Estudos de Coortes , Hospitais
3.
Medicine (Baltimore) ; 103(14): e37512, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579077

RESUMO

ShenGui capsule (SGC), as a herbal compound, has significant effects on the treatment of heart failure (HF), but its mechanism of action is unclear. In this study, we aimed to explore the potential pharmacological targets and mechanisms of SGC in the treatment of HF using network pharmacology and molecular docking approaches. Potential active ingredients of SGC were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform database and screened by pharmacokinetic parameters. Target genes of HF were identified by comparing the toxicogenomics database, GeneCards, and DisGeNET databases. Protein interaction networks and gene-disorder-target networks were constructed using Cytoscape for visual analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes were also performed to identify protein functional annotations and potential target signaling pathways through the DAVID database. CB-DOCK was used for molecular docking to explore the role of IL-1ß with SGC compounds. Sixteen active ingredients in SGC were screened from the traditional Chinese medicine systems pharmacology database and analysis platform, of which 36 target genes intersected with HF target genes. Protein-protein interactions suggested that each target gene was closely related, and interleukin-1ß (IL-1ß) was identified as Hub gene. The network pharmacology analysis suggested that these active ingredients were well correlated with HF. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that target genes were highly enriched in pathways such as inflammation. Molecular docking results showed that IL-1ß binds tightly to SGC active components. This experiment provides an important research basis for the mechanism of action of SGC in the treatment of HF. In this study, the active compounds of SGC were found to bind IL-1ß for the treatment of heart failure.


Assuntos
Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Insuficiência Cardíaca/tratamento farmacológico , Mapas de Interação de Proteínas , Bases de Dados Factuais , Interleucina-1beta , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
4.
Sci Total Environ ; 901: 165904, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-37527708

RESUMO

With the growing development of modern agriculture and industry, groundwater is facing more and more complex contaminants. One such contaminant is per- and polyfluoroalkyl substances (PFASs), which pose a potential risk to human health, particularly for those who rely on groundwater as their primary source of drinking water. In this study, we conducted a comprehensive investigation on the occurrence, spatial distribution, and source apportionment of PFASs in shallow (<60 m) and deep (>80 m) groundwater samples from a reclaimed water irrigation area in Beijing's suburbs. Our results showed that the average total PFAS concentration (∑10PFAS) for all samples was 10.55 ± 7.77 ng/L, ranging from 1.05 to 34.28 ng/L. The dominant congeners were PFBA, PFOA, and PFBS. No significant linear relationship was observed between PFAS concentrations and the well depth. However, the averaged ΣPFASs in groundwater were highest in the uppermost layer and declined sharply to a few ng/L in the deep aquifer below 80 m. PFASs showed elevated concentration in shallow aquifers in 9 out of 11 paired wells, indicating an overall descending trend of PFASs with increasing aquifer depth. The spatial distribution of PFASs was highly heterogeneous and showed different patterns in shallow and deep groundwater, which may be related to the complicated attenuation behavior of PFAS compounds when they transport and diffuse through overlapping aquifer layers. The influence of the landfill on groundwater PFASs was most pronounced within a 5 km radius. Source apportionment results indicated that reclaimed water irrigation is the main non-point source of PFASs in shallow groundwater. In contrast, deep groundwater is primarily subject to point sources and lateral recharge flow. This investigation of PFASs in shallow and deep wells provides a foundation for further exploration of PFASs transportation and risk prevention in regions where groundwater is a major water resource for domestic and industrial development.

5.
World J Psychiatry ; 13(2): 75-83, 2023 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-36925947

RESUMO

BACKGROUND: Major depressive disorder (MDD) is the most frequent reason of disabled people in the world, as reported by the World Health Organization. However, the diagnosis of MDD is mainly based on clinical symptoms. CASE SUMMARY: The clinical, genetic, and molecular characteristics of two Chinese families with MDD are described in this study. There were variable ages of onset and severity in depression among the families. Both Chinese families had a very low pre-valence of MDD. The mitochondrial genomes of these pedigrees were sequenced and indicated a homoplasmic T3394C (Y30H) mutation, with the polymorphism located at a highly conserved tyrosine at position 30 of ND1. The analysis also revealed unique sets of mitochondrial DNA (mtDNA) polymorphisms orig-inating from haplogroups M9a3 and M9a. CONCLUSION: This finding of the T3394C mutation in two unrelated depressed patients provides strong evidence that this mutation may have a part in the etiology of MDD. However, In these two Chinese families having the T3394C mutation, no functional mtDNA mutation was observed. Therefore, T3394C mutations are related with MDD, and the phenotypic manifestation of these mutations may be affected by changes in nuclear genes or environmental factors.

6.
Front Psychiatry ; 14: 1057780, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36824669

RESUMO

Background: Bipolar disorder (BD) is predominantly treated with psychotropic drugs, but BD is a complex medical condition and the contribution of psychotropic drugs is not clear. The objectives of this study are: (1) to present psychotropic drugs used in patients with BD; (2) to access changes of psychotropic drug treatments in acute and maintenance episodes. Methods: The study retrospectively evaluated the medical records of inpatients in the Ningbo Kangning Hospital from January 2019 to December 2019. The medical history of each subject was collected completely, including sociodemographic (gender, age, marital status, and so on) and clinical characteristics at baseline and within 12 months of admission. Results: The study ultimately included 204 patients with BD. After 12 months, 73.0% of the patients still took drugs. Mood stabilizers (72-90%) and antipsychotics (77-95%) were still the most important drugs in patients with BD. Antidepressants (34-40%) and benzodiazepines (20-34%) were the other frequently used drug classes. For mood stabilizers, 40-56% of patients were prescribed lithium. For antipsychotic, 54-65% of patients were prescribed quetiapine. Sertraline (6-9%) and fluoxetine (5-9%) were the antidepressant that most frequently prescribed. Lorazepam (10-18%) was the most commonly used benzodiazepine. In psychotropic polypharmacy, the most frequently taken was mood stabilizer plus antipsychotic co-treatment, about 36-44% of all patients. A total of 35-48% of patients treated by two psychotropic drugs and 24-36% received three. Conclusion: The first 6 months after treatment is very important to medication adherence. Mood stabilizers and antipsychotic remained the primary treatment for BD. Antipsychotic is on the rise in the treatment of BD.

7.
Ir J Med Sci ; 192(2): 615-623, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35657541

RESUMO

BACKGROUND: Essential hypertension (EH) was associated with mitochondrial tRNA mutations. AIMS: This study was designed to assess the association between EH and mitochondrial dysfunction. METHODS: A total of 30 individuals from two different Chinese families exhibit maternally inherited EH were assessed for genetic, clinical, and biochemical phenotypes pertaining to EH and mitochondrial functionality. These analyses included assessments of tRNALeu(UUR) 3261A > G mutation status, mitochondrial membrane permeability, mitochondria-associated ATP and reactive oxygen species (ROS) generation, and electron transport chain functionality. RESULTS: EH was detected in 6 total analyzed members of the two families assessed in the present study, with its initial age of onset and presentation varying among patients. These patients with EH exhibited the tRNALeu(UUR) 3261A > G mutation and were of the B5 and D4 Eastern Asian mitochondrial haplogroups. This 3261A > G mutation was predicted to result in disruption of normal tRNALeu(UUR) activity owing to the destabilization of conserved base pairing (30A-40U). Consistent with this prediction, we found that cybrid cell lines exhibiting this 3261A > G mutation exhibited a ~49.05% decrease in baseline tRNALeu(UUR) levels. These cells additionally exhibited ~44.81% reductions in rates of mitochondrial translation. CONCLUSIONS: To facilitate future molecular diagnosis, the 3261A > G mutation should be included in the list of hereditary risk factors. Our findings will aid in the counseling of EH families.


Assuntos
Mitocôndrias , RNA de Transferência de Leucina , Humanos , RNA de Transferência de Leucina/genética , RNA de Transferência de Leucina/química , RNA de Transferência de Leucina/metabolismo , Linhagem , Mutação , Mitocôndrias/metabolismo , Hipertensão Essencial/genética
8.
Front Immunol ; 13: 1016440, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36458015

RESUMO

Background: Metagenomic next-generation sequencing (mNGS) technology has been central in detecting infectious diseases and helping to simultaneously reveal the complex interplay between invaders and their hosts immune response characteristics. However, it needs to be rigorously assessed for clinical utility. The present study is the first to evaluate the clinical characteristics of the host DNA-removed mNGS technology for detecting SARS-CoV-2, revealing host local immune signaling and assisting genomic epidemiology. Methods: 46 swab specimens collected from COVID-19 patients were assayed by two approved commercial RT-qPCR kits and mNGS. The evolutionary tree of SARS-CoV-2 was plotted using FigTree directly from one sample. The workflow of removing the host and retaining the host was compared to investigate the influence of host DNA removal on the performances of mNGS. Functional enrichment analysis of DEGs and xCell score were used to explore the characteristics of host local immune signaling. Results: The detection rate of mNGS achieved 92.9% (26/28) for 28 samples with a Ct value ≤ 35 and 81.1% (30/37) for all 46 samples. The genome coverage of SARS-CoV-2 could reach up to 98.9% when the Ct value is about 20 in swab samples. Removing the host could enhance the sensitivity of mNGS for detecting SARS-CoV-2 from the swab sample but does not affect the species abundance of microbes RNA. Improving the sequencing depth did not show a positive effect on improving the detection sensitivity of SARS-CoV-2. Cell type enrichment scores found multiple immune cell types were differentially expressed between patients with high and low viral load. Conclusions: The host DNA-removed mNGS has great potential utility and superior performance on comprehensive identification of SARS-CoV-2 and rapid traceability, revealing the microbiome's transcriptional profiles and host immune responses.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiologia , Genômica , DNA , Sequenciamento de Nucleotídeos em Larga Escala , Tecnologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-36554897

RESUMO

(1) Background: Targeting a sample of Chinese employees in this study, the correlation of work stress with changes in quality of life (QoL) was explored subsequent to acute coronary syndrome (ACS). (2) Methods: Patients suffering from the first ACS episode, with regular paid work before ACS, were eligible for this one-year longitudinal study. Effort-reward imbalance (ERI), together with job strain (JS) models, were employed to evaluate work stress before discharge, and QoL prior to discharge (baseline), as well as at 1, 6, and 12 months following discharge, were measured using the 8-Items Short Form (SF-8), in addition to the Seattle Angina Questionnaire (SAQ). Moreover, generalized estimating equations were used to determine the relationship of work stress to longitudinal QoL variations. (3) Results: After adjusting for covariates, high work stress at the baseline measured by JS was associated with the slow recovery of both mental health (p < 0.01) and physical health (p < 0.05) in SF-8, while ERI-measured work stress was related to slower improvement in SF-8 physical health (p < 0.001), SAQ-angina stability (AS) (p < 0.05), SF-8 mental health (p < 0.001), and SAQ-angina frequency (AF) (p < 0.05). After mutual adjustment for JS and ERI, high work stress as assessed by JS displayed no correlation with any QoL alteration (all p > 0.05), whereas ERI-determined work stress at a high level still presented a relationship to slow improvement in SF-8 physical health, SAQ-AS, SF-8 mental health, and SAQ-AF (all p < 0.05). (4) Conclusion: Work stress was associated with slow recovery of QoL in patients with ACS across one year. For ACS patients, ERI was a stronger predictor of QoL variations than JS.


Assuntos
Síndrome Coronariana Aguda , Estresse Ocupacional , Humanos , Qualidade de Vida , Síndrome Coronariana Aguda/epidemiologia , Estudos Longitudinais , Estresse Ocupacional/epidemiologia , Saúde Mental , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Inquéritos e Questionários , Recompensa
10.
J Chin Med Assoc ; 83(8): 761-773, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32780575

RESUMO

BACKGROUND: Surfactant lavage seems to have a good application prospect both in experimental models and patients with meconium aspiration syndrome (MAS). Data regarding the effect of surfactant lavage on pulmonary complications of MAS are conflicting. In view of these uncertainties, an updated meta-analysis including the latest literatures is performed. METHODS: A search was conducted by two investigators involved in this research in PubMed, Embase, and Cochrane databases for studies in English and other languages, in Wanfang, VIP, and Cnki databases for Chinese studies (all last launched on December 18, 2018). Ultimately, we identified 11 original studies, including the surfactant lavage group (n = 189) and the control group (n = 204). Odds ratio and weighted mean difference were calculated using a random effects or fixed effects model, depending on the data type and heterogeneity of the included studies. RESULTS: The comparison of effectiveness on MAS: (1) With respect to oxygen index at 48 hours stage and 72 hours stage, data showed significant difference between surfactant lavage/control groups (we/ighted mean difference [WMD] = -3.37, 95% confidence interval [CI], -5.68 ~ -1.06; p = 0.004 and 95% CI, -5.03 ~ -2.37; p < 0.00001). (2) With respect to days on mechanical ventilation, the analysis showed that there was significant difference between surfactant lavage group and control group (WMD = -1.12, 95% CI, -1.40 ~ -0.84; p < 0.00001). (3) Regarding the need for extracorporeal membrane oxygenation, days of oxygen therapy, and hospital stay, no significant differences were found. The comparison of possible complications of MAS: (1) Regarding pneumothorax, the analysis showed there was significant difference between surfactant lavage and control groups (odds ratio [OR] = 0.46, 95% CI, 0.24 ~ 0.85; p = 0.01). (2) With respect to mortality, persist pulmonary hypertension and pulmonary hemorrhage, the results showed no difference between the two groups. CONCLUSION: With respect to oxygen index and days on mechanical ventilation, surfactant lavage is significantly effective compared with control group, though didn't eventually shorten days of oxygen therapy and hospital stay. In addition, our meta-analysis showed that surfactant lavage does not increase the risk of complications.


Assuntos
Síndrome de Aspiração de Mecônio/tratamento farmacológico , Surfactantes Pulmonares/administração & dosagem , Humanos , Síndrome de Aspiração de Mecônio/complicações , Síndrome de Aspiração de Mecônio/mortalidade , Respiração Artificial , Irrigação Terapêutica
11.
Bioresour Technol ; 309: 123363, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32305849

RESUMO

The piggery digestate of high ammonia was mixed with the anoxic aerated effluent of high nitrate and phosphorus, to cultivate a microalgal-bacterial consortium for simultaneous pollution removal and resource recovery. The highest removal of total inorganic nitrogen was achieved at 324.77 mg/L in 40% piggery digestate mixed with 60% anoxic aerated effluent, along with the most microalgae biomass production. The crude protein and fatty acids of C14-C20 in microalgae cells were 21.80% and 69.78%, indicating that this mixing strategy could produce abundant microalgal biomass suitable for biofuel generation and animal feed. High-throughput sequencing showed that microbial diversity increased and Paenibacillus, Thiopseudomonas and Pseudomonas were the dominant species promoting microalgal growth. Overall, these results provided a new insight of mixing two types of wastewaters for cultivating microalgal-bacterial consortia, to remove contamination and recover nutrients simultaneously.


Assuntos
Microalgas , Animais , Biomassa , Nitrogênio , Fósforo , Águas Residuárias
12.
Environ Sci Pollut Res Int ; 27(12): 12922-12931, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31273659

RESUMO

The international community is paying more and more attention to the role of forests in CO2 absorption. This study aims the broad leaved forest carbon sinks in China, on the basis of research on coniferous forest carbon sinks in 1981 and 2014, the paper analyses the changes in broad leaved forest carbon sinks and the relations between the changes and the forest economics and management from 1981 to 2015 using the forest stock volume conversion method. The paper selects the common indexes of forest economics and management such as investment in forestry-fixed assets in silviculture and afforestation, the annual gross domestic product (GDP) values for the forestry sector, and management level improvement. The paper first of all establishes carbon sink estimates, and then analyses recent carbon sink trends of the dominant species of broad leaved forest which is based on six times inventories of China's forest resources. The inventory data cover the four dominant broad-leaved species which are named as Oak, Betula, Populus, and others, such as Eucalyptus, Camphor, and Linden. The paper shows that a significant effect has been made by the forest carbon sinks of these species and investment in forestry-fixed assets in silviculture and afforestation, management level improvement etc. though with a lag of 4-7 years, and there raises a lot of discussions of various problems regarding forest carbon sinks and forest management and economic development. This study has important implications for forest resource management and climate change mitigation.


Assuntos
Sequestro de Carbono , Árvores , Carbono/análise , China , Florestas
13.
Front Psychol ; 7: 1552, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27803679

RESUMO

Earthquake survivors are a diverse population. This study focused on a special group of earthquake survivors, who had still stayed in temporary housing camps for about 2 years after China's Wenchuan Earthquake rather than those who moved back to rebuild their lives or immigrated to large cities to seek new lives. The research goals were to (1) assess their sleep problems as well as their PTSD, depression and anxiety and (2) examine the relationship between different dimensions of sleep quality and PTSD, depression, and anxiety among these survivors. Three-hundred and eighty seven earthquake survivors who remained in temporary housing camps and had sleep problems were recruited 17-27 months after Wenchuan Earthquake. Four standardized instruments-The Pittsburgh Sleep Quality Index, PTSD Checklist-Civilian Version, Self-rating Depression Scale, Self-rating Anxiety Scale, and face-to-face one-on-one structured interviews were used to assess these survivors' sleep quality, PTSD, depression, and anxiety. It was found that (1) 83.20% of these survivors reported having sleep problems, and 79.33% of them considered insomnia as the most common sleep problem; (2) 12.14% suffered PTSD, 36.43% experienced depression, and 38.24% had anxiety; (3) sleep disturbance, sleep medication use, and subjective sleep quality were significantly related to PTSD; (4) habitual sleep efficiency, sleep disturbance, sleep medication use, and daytime dysfunction were significantly related to depression; and (5) sleep disturbance, sleep medication use, and daytime dysfunction were significantly related to anxiety. Clinic implications of the study are discussed.

14.
Hepatobiliary Pancreat Dis Int ; 14(4): 386-93, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26256083

RESUMO

BACKGROUND: Steatotic liver grafts, although accepted, increase the risk of poor posttransplantation liver function. However, the growing demand for adequate donor organs has led to the increased use of so-called marginal grafts. Liver X receptor alpha (LXRalpha) is important in fatty acid metabolism and interrelated with the specific ischemia-reperfusion injury in fatty liver transplantation. This study aimed to investigate whether LXRalpha RNA interference (RNAi) could improve the organ function of liver transplant recipients. METHODS: Fifty Sprague-Dawley rats were fed with a high-fat diet and 56% alcohol. The livers of these animals had greater than 60% macrovesicular steatosis and were used as liver donors. The experimental donors were treated with 7X107 TU LXRalpha-RNAi-LV of a mixture injection and control donors with negative control-LV vector injection into the portal vein 72 hours before the operation. The effects of LXRalpha-RNAi-LV were assessed by serum aminotransferases, histology, immunostaining, and protein levels. The transcription of LXRalpha mRNA was assessed by reverse transcription-polymerase chain reaction. RESULTS: Compared with controls, LXRalpha RNAi inhibited the expression of LXRalpha at the mRNA (0.53+/-0.03 vs 0.94+/-0.02, P<0.05) and protein levels (0.51+/-0.08 vs 1.09+/-0.12, P<0.05). LXRalpha RNAi also decreased the expressions of sterol regulatory element-binding protein 1c (SREBP-1c) and CD36. LXRalpha RNAi consequently reduced fatty acid accumulation in hepatocytes. Compared with control animals, LXRalpha RNAi-treated group had lower serum alanine aminotransferase, aspartate aminotransferase, interleukin-1beta, and tumor necrosis factor-alpha levels and milder pathologic damages. TUNEL analysis revealed a significant reduction of apoptosis in the livers of rats treated with LXRalpha-RNAi-LV, and overall survival as determined by the Kaplan-Meier method was improved among rats treated with LXRalpha-RNAi-LV (P<0.05). CONCLUSION: LXRalpha-RNAi-LV treatment significantly downregulated LXRalpha expression and improve steatotic liver graft function and recipient survival after a fatty liver transplantation in rats.


Assuntos
Fígado Gorduroso/cirurgia , Técnicas de Transferência de Genes , Vetores Genéticos , Lentivirus/genética , Transplante de Fígado/métodos , Fígado/cirurgia , Receptores Nucleares Órfãos/genética , RNA Interferente Pequeno/genética , Terapêutica com RNAi/métodos , Animais , Apoptose , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação para Baixo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Sobrevivência de Enxerto , Fígado/metabolismo , Fígado/patologia , Receptores X do Fígado , Receptores Nucleares Órfãos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo
15.
PLoS One ; 8(8): e72015, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23977195

RESUMO

UBIAD1 plays critical roles in physiology including vitamin K and CoQ10 biosynthesis as well as pathophysiology including dyslipimedia-induced SCD (Schnyder's corneal dystrophy), Parkinson's disease, cardiovascular disease and bladder carcinoma. Since the subcellular localization of UBIAD1 varies in different cell types, characterization of the exact subcellular localization of UBIAD1 in specific human disease is vital for understanding its molecular mechanism. As UBIAD1 suppresses bladder carcinoma, we studied its subcellular localization in human bladder carcinoma cell line T24. Since fluorescent images of UBIAD1-EGFP in T24, human prostate cancer cell line PC-3, human embryonic kidney cell line HEK293 and human hepatocyte cell line L02 are similar, these four cell lines were used for present study. Using a combination of fluorescent microscopy and immunohistochemistry, it was found that UBIAD1 localized on the Golgi and endoplasmic reticulum (ER), but not on the plasma membrane, of T24 and HEK293 cells. Using scanning electron microscopy and western blot analysis, we found that UBIAD1 is enriched in the Golgi fraction extracted from the L02 cells, verifying the Golgi localization of UBAID1. Site-directed mutagenesis showed that the RPWS motif, which forms an Arginine finger on the UBIAD1 N terminus, serves as the Golgi retention signal. With both cycloheximide and brefeldin A inhibition assays, it was shown that UBIAD1 may be transported from the endoplasmic reticulum (ER) to the Golgi by a COPII-mediated mechanism. Based upon flow cytometry analysis, it is shown that mutation of the RPWS motif reduced the UBIAD1-induced apoptosis of T24 cells, indicating that the proper Golgi localization of UBIAD1 influences its tumor suppressant activity. This study paves the way for further understanding the molecular mechanism of UBIAD1 in human diseases.


Assuntos
Dimetilaliltranstransferase/metabolismo , Complexo de Golgi/enzimologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Linhagem Celular Tumoral , Dimetilaliltranstransferase/química , Dimetilaliltranstransferase/genética , Retículo Endoplasmático/enzimologia , Genes Supressores de Tumor , Células HEK293 , Humanos , Microscopia de Fluorescência , Dados de Sequência Molecular , Sinais Direcionadores de Proteínas , Transporte Proteico
16.
Transl Neurodegener ; 1(1): 7, 2012 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-23211059

RESUMO

BACKGROUND: Several studies indicated that Erythropoietin (Epo) may provide remarkable neuroprotection in some neurological diseases. It also showed the significant decrease of Epo immunoreactivity in the cerebral cortex and hippocampus in aged rats, suggesting the role of Epo in the pathogenesis of age-related neurodegenerative diseases such as AD. METHODS: The protective effect of Epo was studied in differentiated PC12 cells treated with Abeta. The viability of the cells, the apoptosis of the cells and the level of Bax, Bcl-2, cleaved caspase-3 and cleaved PARP expression were detected by MTT, Hoechst 33258 staining and Western blotting respectively. RESULTS: 20 µM Abeta (25-35) could induce a decreased viability and a increased apoptosis in PC12 cell in a time-dependent manner. However, 20 µM Abeta (35-25) had no effect on cell viability and apoptosis. Western blot analysis also showed that Abeta(25-35) treatment could decrease the expression of Bcl-2 (P < 0.05) and increase the expression of Bax (P < 0.05), Cleaved casapase-3 (P < 0.05), and Cleaved PARP (P < 0.05). The pretreatment of Epo could effectively reverse all the above changes induced by Abeta(25-35) (P < 0.05). Furthermore, the protective effect of Epo could be blocked by PI3K inhibitor LY294002 (P < 0.05). CONCLUSIONS: Epo prevented cell injuries in PC12 cells exposed to the Abeta(25-35) and this effect may depend on the PI3K/Akt pathway. Our study provided an important evidence for the potential application of Epo in the therapy of Alzheimer's disease.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA