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1.
Neurobiol Dis ; 132: 104567, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394202

RESUMO

Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aß) accumulation. However, the mechanism by which Aß induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aß and mediates Aß neurotoxicity, implying that p75NTR may mediate Aß-induced tau phosphorylation in AD. Here, we showed that Aß-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3ß (GSK3ß) significantly changed Aß/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aß to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aß-induced tau pathology and is a potential druggable target for AD and other tauopathies.

2.
Neurotox Res ; 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31209785

RESUMO

Parkinson's disease (PD) is attributed to interactions among genes and environmental and lifestyle factors, but the genetic architecture of PD is complex and not completely understood. To evaluate whether the genetic profile modifies PD development and cerebrospinal fluid (CSF) pathological biomarkers, we enrolled 418 PD patients and 426 age- and sex-matched normal controls. Forty-six single nucleotide polymorphisms (SNPs) that were reported to be significantly associated with PD in large-scale genome-wide association studies (GWASs) were genotyped and analysed. The alleles associated with PD were used to build polygenic risk score (PRS) models to represent polygenic risk. The Cox proportional hazards model and receiver operating characteristic (ROC) analyses were used to evaluate the prediction value of the PRS for PD risk and age at onset. The CSF α-synuclein levels were measured in a subgroup of control subjects (n = 262), and its relationship with the PRS was analysed. We found that some SNPs identified from other populations had significant correlations with PD in our Chinese cohort. The PRS we built had prediction value for PD risk and age at onset. The CSF α-synuclein level had no correlation with the PRS in normal subjects.

3.
Neurotox Res ; 36(1): 101-107, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30977102

RESUMO

The neurotrophin receptor p75 (p75NTR) plays important roles in regulating amyloid-beta (Aß) metabolism in the brain. The expression of p75NTR is altered in the brain of patients with Alzheimer's disease (AD). In this study, we aimed to evaluate whether p75NTR mRNA level in the peripheral blood cells is changed among AD patients and its potential to be a biomarker for AD. The study subjects included 26 patients with AD (PiB-PET positive) and 28 cognitively normal controls (PiB-PET negative). RNA was extracted from peripheral blood cells of fast blood. p75NTR mRNA was measured using quantitative real-time PCR assay. p75NTR mRNA levels in blood cells were comparable between AD patients and controls. p75NTR mRNA levels in blood cells were not correlated with MMSE scores, ApoE genotypes, gender, and age. p75NTR mRNA expression in blood cells is not changed in AD patients and is unlikely to be a biomarker for AD.

4.
Neurotox Res ; 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30941646

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease characterized by neuronal loss in the substantia nigra. The p75 neurotrophin receptor (p75NTR, encoded by NGFR) was found to play an important role in the selective neuronal death of dopamine neurons in the substantia nigra, as well as the pathogenesis and development of PD. To assess the association between NGFR gene polymorphism and the susceptibility of PD, this case-control study consisting of 414 PD patients and 623 age- and sex-matched controls in a Chinese Han cohort was conducted. Twelve tag-single nucleotide polymorphisms (tag-SNPs) were selected from the NGFR gene through the construction of linkage disequilibrium blocks. One tag-SNP from the ADAM17 gene was also selected owing to its function of encoding tumor necrosis factor α-converting enzyme, which is responsible for the shedding of the extracellular domain of p75NTR. A multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method was applied for genotyping. The associations between tag-SNPs and the risk of PD with the adjustment for age and sex were analyzed by unconditional logistic regression, and five genetic models including codominant, dominant, recessive, over-dominant, and additive models were applied. The results showed that among the 13 tag-SNPs, rs741073 was associated with a reduced risk of PD in the codominant (OR = 0.71, 95% CI = 0.54-0.93, P = 0.037), dominant (OR = 0.76, 95% CI = 0.58-0.98, P = 0.033), and over-dominant models (OR = 0.71, 95% CI = 0.54-0.92, P = 0.010), and rs1804011 was also associated with a reduced risk of PD in the codominant (OR = 0.69, 95% CI = 0.50-0.95, P = 0.049), dominant (OR = 0.69, 95% CI = 0.50-0.93, P = 0.014), over-dominant (OR = 0.70, 95% CI = 0.51-0.96, P = 0.025), and additive models (OR = 0.72, 95% CI = 0.54-0.94, P = 0.016). However, these associations did not retain after Bonferroni correction. Conclusively, our study failed to reveal the association between the selected tag-SNPs within NGFR, ADAM17, and the susceptibility of PD. The role of p75NTR and its gene polymorphisms in the pathogenesis of PD needs to be further studied.

5.
Ann Clin Transl Neurol ; 6(4): 788-794, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31020003

RESUMO

Objective: Obstructive sleep apnea syndrome (OSAS) is characterized by nocturnal intermittent hypoxemia and can increase the risk of Parkinson's disease. This study aimed to investigate the association between plasma α-synuclein levels and hypoxia in the patients with OSAS. Methods: We recruited 42 OSAS patients and 46 controls with simple snoring matched for age and gender. OSAS was diagnosed on the basis of the clinical symptoms as well as the nighttime polysomnography. Plasma total α-synuclein and phosphorylated α-synuclein levels were measured by ELISA kits. Results: The OSAS patients had significant higher levels of plasma total α-synuclein and phosphorylated α-synuclein levels. Both of the above indexes were positively correlated with the apnea-hypopnea index and the oxygen desaturation index, while they were negatively correlated with the mean and lowest oxyhemoglobin saturations. Interpretation: This study suggests that chronic intermittent hypoxia can increase the α-synuclein levels, which may contribute to the pathogenesis of Parkinson's disease.

6.
Nucleic Acids Res ; 47(8): 4111-4123, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30767010

RESUMO

Single-stranded DNA-binding proteins (SSBs) support DNA replication by protecting single-stranded DNA from nucleolytic attack, preventing intra-strand pairing events and playing many other regulatory roles within the replisome. Recent developments in single-molecule approaches have led to a revised picture of the replisome that is much more complex in how it retains or recycles protein components. Here, we visualize how an in vitro reconstituted Escherichia coli replisome recruits SSB by relying on two different molecular mechanisms. Not only does it recruit new SSB molecules from solution to coat newly formed single-stranded DNA on the lagging strand, but it also internally recycles SSB from one Okazaki fragment to the next. We show that this internal transfer mechanism is balanced against recruitment from solution in a manner that is concentration dependent. By visualizing SSB dynamics in live cells, we show that both internal transfer and external exchange mechanisms are physiologically relevant.

7.
Int J Mol Med ; 43(3): 1531-1541, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664181

RESUMO

Dogs are a major source of indoor allergens. However, the prevalence of dog allergies in China remains unclear, especially in children. In the present study, Can f 7, a canine allergen belonging to the Niemann pick type C2 protein family, was selected to study its sensitization rate in Chinese children with dog allergies. The Can f 7 gene was subcloned into a pET­28a vector and expressed in Escherichia coli BL21 (DE3) cells. Recombinant Can f 7 was purified by nickel affinity chromatography, identified by SDS­PAGE electrophoresis, and had its allergenicity assessed by western blot, ELISA and basophil activation tests. Through a series of bioinformatical approaches, B­cell epitopes, secondary structures, and 3 dimensional (3D) homology modeling of Can f 7 were predicted. The activity of the B cell epitopes was verified by ELISA. The recombinant Can f 7 showed a distinct band with a molecular weight of 14 kDa. Six of 20 sera from dog­allergic children reacted positively to the Can f 7. Can f 7 induced an ~4.0­fold increase in cluster of differentiation 63 and C­C motif chemokine receptor R3 expression in basophils sensitized with the serum of dog­allergic children compared with those of non­allergic controls. The secondary structure analysis showed that Can f 7 contains 6 ß­sheets. Five B cell epitopes of Can f 7 were predicted, and two of these were confirmed by ELISA. These results indicate that Can f 7 is an important canine allergen in Chinese children and provide novel data for further research concerning the use of Can f 7 in the diagnosis and treatment of Chinese children with canine allergy symptoms.


Assuntos
Alérgenos/genética , Alérgenos/imunologia , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Expressão Gênica , Lipocalinas/genética , Lipocalinas/imunologia , Adolescente , Alérgenos/química , Alérgenos/isolamento & purificação , Sequência de Aminoácidos , Animais , Criança , Pré-Escolar , Códon , Cães , Ensaio de Imunoadsorção Enzimática , Epitopos de Linfócito B/química , Feminino , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Lactente , Lipocalinas/química , Lipocalinas/isolamento & purificação , Masculino , Modelos Moleculares , Conformação Proteica , Proteínas Recombinantes
8.
Curr Opin Struct Biol ; 53: 159-168, 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30292863

RESUMO

Bacterial replisomes are dynamic multiprotein DNA replication machines that are inherently difficult for structural studies. However, breakthroughs continue to come. The structures of Escherichia coli DNA polymerase III (core)-clamp-DNA subcomplexes solved by single-particle cryo-electron microscopy in both polymerization and proofreading modes and the discovery of the stochastic nature of the bacterial replisomes represent notable progress. The structures reveal an intricate interaction network in the polymerase-clamp subassembly, providing insights on how replisomes may work. Meantime, ensemble and single-molecule functional assays and fluorescence microscopy show that the bacterial replisomes can work in a decoupled and uncoordinated way, with polymerases quickly exchanging and both leading-strand and lagging-strand polymerases and the helicase working independently, contradictory to the elegant textbook view of a highly coordinated machine.

9.
Anal Biochem ; 557: 42-45, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30016625

RESUMO

Rolling-circle DNA amplification is a powerful tool employed in biotechnology to produce large from small amounts of DNA. This mode of DNA replication proceeds via a DNA topology that resembles a replication fork, thus also providing experimental access to the molecular mechanisms of DNA replication. However, conventional templates do not allow controlled access to multiple fork topologies, which is an important factor in mechanistic studies. Here we present the design and production of a rolling-circle substrate with a tunable length of both the gap and the overhang, and we show its application to the bacterial DNA-replication reaction.

10.
Mol Psychiatry ; 23(8): 1813-1824, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29867188

RESUMO

Tau pathology is characterized as a form of frontotemporal lobar degeneration (FTLD) known as FTLD-tau. The underlying pathogenic mechanisms are not known and no therapeutic interventions are currently available. Here, we report that the neurotrophin receptor p75NTR plays a critical role in the pathogenesis of FTLD-tau. The expression of p75NTR and the precursor of nerve growth factor (proNGF) were increased in the brains of FTLD-tau patients and mice (P301L transgenic). ProNGF-induced tau phosphorylation via p75NTR in vitro, which was associated with the AKT/glycogen synthase kinase (GSK)3ß pathway. Genetic reduction of p75NTR in P301L mice rescued the memory deficits, alleviated tau hyperphosphorylation and restored the activity of the AKT/GSK3ß pathway. Treatment of the P301L mice with the soluble p75NTR extracellular domain (p75ECD-Fc), which can antagonize neurotoxic ligands of p75NTR, effectively improved memory behavior and suppressed tau pathology. This suggests that p75NTR plays a crucial role in tau paGSKthology and represents a potential druggable target for FTLD-tau and related tauopathies.

11.
Medicine (Baltimore) ; 97(23): e10891, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29879024

RESUMO

The aim of this study was to evaluate the relationship between interleukin-21 (IL-21) and interleukin-21 receptor (IL-21R) polymorphisms and the response to peginterferon alfa (PEG-IFN α) therapy in HBeAg-positive chronic hepatitis B (CHB) patients.A total of 143 HBeAg-positive CHB patients treated for 48 weeks with PEG-IFN α and followed up for 24 weeks post-treatment were retrospectively evaluated. Genotypes analysis was performed for IL-21 polymorphisms rs907715, rs2221903, and IL-21R polymorphisms rs3093301 and rs2285452. Serum IL-21 levels were measured by enzyme-linked immunosorbent assay.The end of virological response (EVR) rate was 46.9% (67/143) at the end of treatment, the sustained virological response (SVR) rate was 43.4% (62/143) and the complete response (CR) rate was 32.1% (46/143) at 24 weeks post-treatment. Patients who carried IL-21 rs 2221903 genotype AA had a rather higher rate of EVR (response rate: 52.4%, odds ratio [OR] 0.42, 95% confidence interval [CI]: 0.19-0.91, P = .021), SVR (response rate: 47.6%, OR 0.43, 95% CI: 0.19-0.95, P = .028), and CR (response rate: 38.1%, OR 0.31, 95% CI: 0.12-0.79, P = .014) when compared to those had AG genotype. Meanwhile, IL-21rs 2221903 genotype AA was also independently associated with markedly reduced HBsAg levels (>1og10 IU/mL) after 24 weeks treatment and low HBsAg levels (<100 IU/mL) at the end of treatment. IL-21 rs907715 AG/GG genotype was independently associated with SVR (OR: 2.92, 95% CI: 0.98-8.6, P = .039; OR: 3.23, 95% CI: 1.0-10.4, P = .039). Patients with IL-21 rs907715 AG/GG genotype had higher serum IL-21 levels than those with rs907715 AA genotype (P = .021).IL-21 rs2221903 and rs907715 polymorphisms were significantly associated with the treatment response to PEG-IFN α among Chinese HBeAg-positive CHB patients.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Interleucinas/genética , Receptores de Interleucina-21/genética , Adulto , Grupo com Ancestrais do Continente Asiático , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B , Hepatite B Crônica/genética , Humanos , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resposta Viral Sustentada , Resultado do Tratamento , Adulto Jovem
12.
J Stroke Cerebrovasc Dis ; 27(7): 1992-1997, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29673615

RESUMO

BACKGROUND: To investigate the effects of abdominal obesity (AO) and nonalcoholic fatty liver disease (NAFLD) with or without AO on carotid arteries by determining carotid intima-media thickness (CIMT). METHODS: A total of 2745 Chinese Han adults (aged between 40 and 50 years old) were recruited and divided into 4 groups: (1) NW-no NAFL group: the normal body weight without NAFLD (n = 1888); (2) AO-no NAFL group: AO without NAFLD (n = 259); (3) NW-with NAFL group: NAFLD without AO (n = 93); and (4) AO-with NAFL group: AO with NAFLD (n = 505). The CIMT rate of each group was compared among 4 groups and the regression analysis was further used to correct confounders. RESULTS: We found that the NW-with NAFL group had a significantly higher CIMT rate than the AO-no NAFL group ([.87 ± .31] versus [.72 ± .29] P < .01) and the AO-with NAFL group ([.87 ± .31] versus [.79 ± .26], P < .01). CONCLUSIONS: The ectopic liver fat accumulation may increase the risk of atherosclerosis. Therefore, screening NAFLD in the population with normal weight may be beneficial for the prevention of atherosclerosis at an early stage.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Obesidade Abdominal/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Adulto , Aterosclerose/diagnóstico por imagem , Composição Corporal , China , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco
13.
Antibiotics (Basel) ; 7(1)2018 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-29470422

RESUMO

In bacteria, the DnaG primase is responsible for synthesis of short RNA primers used to initiate chain extension by replicative DNA polymerase(s) during chromosomal replication. Among the proteins with which Escherichia coli DnaG interacts is the single-stranded DNA-binding protein, SSB. The C-terminal hexapeptide motif of SSB (DDDIPF; SSB-Ct) is highly conserved and is known to engage in essential interactions with many proteins in nucleic acid metabolism, including primase. Here, fragment-based screening by saturation-transfer difference nuclear magnetic resonance (STD-NMR) and surface plasmon resonance assays identified inhibitors of the primase/SSB-Ct interaction. Hits were shown to bind to the SSB-Ct-binding site using 15N-¹H HSQC spectra. STD-NMR was used to demonstrate binding of one hit to other SSB-Ct binding partners, confirming the possibility of simultaneous inhibition of multiple protein/SSB interactions. The fragment molecules represent promising scaffolds on which to build to discover new antibacterial compounds.

14.
J Neurol Sci ; 383: 175-179, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29246609

RESUMO

BACKGROUND: There has been no effective treatment for acute ischemic stroke (AIS) patients who presented to the Emergency Department >4.5h without a visible arterial occlusion on the neurovascular imaging studies. In this study, we aimed to investigate whether intravenous antiplatelet agent tirofiban was safe and potentially effective in AIS patients who had no visible arterial occlusion and was outside of treatment window for Alteplase. The goal of this study was to collect preliminary data to plan a future phase II study. METHOD: Twenty-five patients received intravenous tirofiban therapy. The safety outcomes were assessed by the incidence of symptomatic intracerebral hemorrhage (sICH), systematic bleeding and mortality. Efficacy outcomes were evaluated with National Institutes of Health Stroke Scale (NIHSS) score at day 7 (or discharge) and modified Rankin Scale (mRS) at 90days. Outcomes for these patients were compared with a historical age-gender-admission-NIHSS matched cohort treated with aspirin and/or clopidogrel. RESULTS: The rate of intracerebral hemorrhage, systematic bleedings, and death were not found in both groups. At day 7 or discharge, the neurological function improved significantly in both treatment groups. However, the NIHSS score was lower in tirofiban group compared with the control group (2 vs.3, p=0.045). At 3months, more patients in tirofiban group had favorable outcomes (mRS 0-1) compared with control group (84% vs. 52%; adjusted odds ratio: 10.57; 95% CI: 1.54-72.33; p=0.016). CONCLUSIONS: Intravenous tirofiban appears to be safe and potentially effective for the ischemic stroke patients with no artery occlusion on neurovascular imaging studies and being out of the window for thrombolytic therapy. A next logic step is to plan for a phase II study.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Tirosina/análogos & derivados , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Angiografia Cerebral , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , Angiografia por Tomografia Computadorizada , Imagem de Difusão por Ressonância Magnética , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Tempo para o Tratamento , Tirofibana , Resultado do Tratamento , Tirosina/administração & dosagem , Tirosina/efeitos adversos
15.
Neurosci Bull ; 33(6): 703-710, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29134450

RESUMO

Dementia is increasing dramatically and imposes a huge burden on society. To date, there is a lack of data on the health status of patients with dementia in China. In an attempt to investigate the comorbidity burden of dementia patients in China at the national level, we enrolled 2,938 patients with Alzheimer's disease (AD), vascular dementia (VaD), or other types of dementia, who were admitted to tertiary hospitals in seven regions of China from January 2003 to December 2012. The Charlson Comorbidity Index (CCI) was used to evaluate the comorbidity burden of the patients with dementia. Among these patients, 53.4% had AD, 26.3% had VaD, and 20.3% had other types of dementia. The CCI was 3.0 ± 1.9 for all patients, 3.4 ± 1.8 for those with VaD, and 3.0 ± 2.1 for those with AD. The CCI increased with age in all patients, and the length of hospital stay and daily expenses rose with age and CCI. Males had a higher CCI and a longer stay than females. Moreover, patients admitted in the last 5 years of the study had a higher CCI than those admitted in the first 5 years. We found that the comorbidity burden of patients with dementia is heavy. These findings provide a better understanding of the overall health status of dementia patients, and help to increase the awareness of clinicians and policy-makers to improve medical care for patients.


Assuntos
Doença de Alzheimer/epidemiologia , Comorbidade , Demência Vascular/epidemiologia , Demência/epidemiologia , Hospitalização/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Hospitalização/economia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores Sexuais
16.
Sci Total Environ ; 607-608: 558-567, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28704678

RESUMO

The oxic-settling-anoxic (OSA) process, which involves an aerobic tank attached to oxygen- and substrate-deficient external anoxic reactors, minimizes sludge production in biological wastewater treatment. In this study, the microbial community structure of OSA was determined. Principal coordinate analysis showed that among the three operational factors, i.e., (i) redox condition, (ii) external reactor sludge retention time (SRText), and (iii) sludge interchange between aerobic and anoxic reactors, redox condition had the greatest impact on microbial diversity. Generally, reactors with lower oxidation-reduction potential had higher microbial diversity. The main aerobic sequencing batch reactor of OSA (SBROSA) that interchanged sludge with an external anoxic reactor had greater microbial diversity than SBRcontrol which did not have sludge interchange. SBROSA sustained high abundance of the slow-growing nitrifying bacteria (e.g., Nitrospirales and Nitrosomondales) and consequently exhibited reduced sludge yield. Specific groups of bacteria facilitated sludge autolysis in the external reactors. Hydrolyzing (e.g., Bacteroidetes and Chloroflexi) and fermentative (e.g., Firmicutes) bacteria, which can break down cellular matter, proliferated in both the external aerobic/anoxic and anoxic reactors. Sludge autolysis in the anoxic reactor was enhanced with the increase of predatory bacteria (e.g., order Myxobacteriales and genus Bdellovibrio) that can contribute to biomass decay. Furthermore, ß- and γ-Proteobacteria were identified as the bacterial phyla that primarily underwent decay in the external reactors.

18.
Sci Rep ; 7(1): 1671, 2017 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-28490759

RESUMO

Parkinson's disease (PD) and Parkinsonism are common neurodegenerative disorders with continuously increasing prevalence, causing high global burdens. However, data concerning the comorbidity burden of patients with PD or Parkinsonism in China are lacking. To investigate the health condition and comorbidity burden, a total of 3367 PD and 823 Parkinsonism patients were included from seven tertiary hospitals in seven cities across China from 2003 to 2012. Their comorbidity burden was collected and quantified by the Elixhauser Comorbidity Index (ECI) and Charlson Comorbidity Index (CCI). The comorbidity spectra differed between PD and Parkinsonism patients. Compared with PD patients, Parkinsonism patients were older (69.8 ± 11.5 vs. 67.9 ± 11.4, P < 0.001); had a higher comorbidity burden, including ECI (1.1 ± 1.2 vs. 1.0 ± 1.2, P < 0.001) and CCI (1.3 ± 1.6 vs. 1.1 ± 1.5, P < 0.001); and had higher hospitalization expenses. The ECI (1.1 ± 1.3 vs. 0.9 ± 1.1, P < 0.001) and CCI (1.3 ± 1.6 vs. 0.9 ± 1.2, P < 0.001) were higher in males than in females. The average length of stay and daily hospitalization expenses increased with age, as did ECI and CCI. This is the first study to report the disease burden of Chinese PD and Parkinsonism patients. It provides useful information to better understand their health status, and to raise the awareness of clinicians for providing better health care.

19.
Oxid Med Cell Longev ; 2017: 4130824, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28392886

RESUMO

The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP (tert-butyl hydroperoxide). The results showed that pretreatment with amifostine significantly attenuated cell apoptosis and death, accompanied by decreased reactive oxygen species (ROS) production and lower mitochondrial potential (ΔΨm). In vivo, amifostine pretreatment alleviated I/R injury and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase (SOD) and reduced malondialdehyde (MDA) in myocardial tissues, increased Bcl2 expression, decreased Bax expression, lower cleaved caspase-3 level, fewer TUNEL positive cells, and fewer DHE-positive cells in heart. Our results indicate that amifostine pretreatment has a protective effect against myocardial I/R injury via scavenging ROS.


Assuntos
Amifostina/farmacologia , Amifostina/uso terapêutico , Apoptose/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Camundongos , Mitocôndrias/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Profilaxia Pré-Exposição , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico
20.
Int J Biol Sci ; 12(11): 1357-1362, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27877087

RESUMO

Clinical data on children with chronic hepatitis C (CHC) remain extremely limited. This study investigated sustained virologic response (SVR) to alfa-interferon 2b plus RBV treatment in children aged 1-6 years with unsafe injection-acquired CHC. 154 children with CHC aged 1 to 6 years were enrolled, 101 of them were male (65.6%) and 53 were female (34.4%), and they were treated with alfa-interferon at a dose of 1-5 MIU/m2 3 times weekly plus oral RBV (15 mg/kg/day) for 48 weeks. 57(39.3 %) of them were genotype 1b, 73(50.3%) were genotypes 2a, 15(10.3%) were undecided type. SVR was achieved in 53 of 57(93.0%) patients with genotype 1b, in 72 (98.6%) of 73 with genotype 2a, 15(100.0%) of 15 with undecided type. There was no significant statistical difference in SVR between male and female (98.0% vs 94.3%, p=0.340), genotype 2a and those with genotype 1b(98.6% vs 93.0%, p=0.160), ALT>40U/L group and ALT≤40U/L group(96.7% vs 96.8%, p=1.000), AST>40U/L group and AST≤40U/L group(95.9% vs 98.2%, p=0.654) as well as lower baseline viral load group (<6×105 IU/ml) and higher baseline viral load group(≥6×105 IU/ml)(97.3% vs 95.3%, p=0.916). Leucopenia, neutropenia, hemoglobin concentration decrease, fever, platelet count decrease and rash were 8.4%, 69.5%, 24.0%, 50.6%, 1.9% and 4.5%, respectively. And only 12(7.8%) individuals developed thyroid autoantibodies. The SVR was higher in patients with IL-28B genotype C/C than C/T (99.0% vs 80%, p=0.002). Compared with HCV viral genotype, ALT level and baseline viral load, IL-28B rs12979860 is more suitable for predicting antiviral efficacy in children with CHC. It is inappropriate to take the increase of ALT level as an essential indicator for antiviral treatment in children aged 1-6 years.


Assuntos
Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Interleucinas/genética , Polimorfismo de Nucleotídeo Único/genética , Resposta Viral Sustentada , Antivirais/uso terapêutico , Criança , Pré-Escolar , Feminino , Genótipo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Humanos , Lactente , Interferon-alfa/uso terapêutico , Masculino , Carga Viral/efeitos dos fármacos
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