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1.
Rheumatol Int ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499196

RESUMO

In view of the possible involvement of vascular endothelial growth factor-C (VEGF-C) in pathogenesis of adult-onset Still's disease (AOSD) based on our previous genome-wide association study (GWAS) results, the primary objective of this study, therefore, was to investigate the correlations between the content of VEGF-C in serum and clinical and biochemical markers of AOSD. Blood samples were collected from 80 patients with AOSD, 26 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE) and 31 healthy control subjects. The serum VEGF-C levels were determined using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis and comparisons were conducted. A significantly higher serum VEGF-C level was observed in patients with AOSD than in HC. Serum VEGF-C levels had high AUC value of 0.8145 for distinguishing AOSD group from healthy group with sensitivity of 0.7097 and specificity of 0.8250. It also showed good diagnostic value to differentiate AOSD from other autoinflammatory diseases with sensitivity of 0.7500 and specificity of 0.5500. AOSD patients with fever, arthralgia, skin rash, sore throat, lymphadenopathy, splenomegaly hepatomegaly and pleuritis, had a higher level than those who did not have these symptoms (p = 0.0012, p = 0.0092, p = 0.0056, p = 0.0123, p = 0.0068, p = 0.0030, p = 0.0020, and p = 0.0018, respectively). The serum VEGF-C levels were also positively correlated with laboratory features and several cytokines related to AOSD disease activity. In conclusion, our study unveiled a close association between serum VEGF-C levels and AOSD including disease activity and clinical hematological manifestations, suggesting the potential utility of VEGF-C as a candidate biomarker to assess disease activity in AOSD.

2.
Int J Rheum Dis ; 24(10): 1247-1256, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34314100

RESUMO

BACKGROUND: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. METHODS: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. RESULTS: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. CONCLUSIONS: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

3.
Front Immunol ; 12: 654811, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868298

RESUMO

Adult-onset Still's disease (AOSD) is a systemic, multifactorial, autoinflammatory disease for which the etiopathogenesis is not well understood. Given the similarities in clinical and laboratory features between this disease and sepsis, and the differences in treatment strategies for these two diseases, specific diagnostic markers are crucial for the correct diagnosis and management of AOSD. Previous studies have shown plasma heparin-binding protein (HBP) is a promising potential biomarker for AOSD; thus, this study aimed to detect serum HBP levels in patients with AOSD or sepsis to assess its potential as a biomarker for differential diagnosis. We found that serum HBP levels were significantly higher in patients with active AOSD than that in those with inactive AOSD. Patients with sepsis had higher serum HBP levels compared with those who had active or inactive AOSD. We calculated the area under the receiver operating characteristic (ROC) curve to assess whether HBP could be used to differentiate active from inactive AOSD; this was 0.811 with sensitivity 0.650, specificity 0.811, and cutoff HBP value of 35.59 ng/ml. The area under the ROC curve for HBP as a biomarker to differentiate AOSD from sepsis was 0.653, with sensitivity 0.759, and specificity 0.552, and cutoff HBP value of 65.1 ng/ml. Taken together, the results of our study suggest that serum HBP could be a useful diagnostic biomarker to evaluate disease activity in patients with AOSD, and to differentiate AOSD from sepsis.


Assuntos
Peptídeos Catiônicos Antimicrobianos/sangue , Biomarcadores/sangue , Sepse/sangue , Sepse/diagnóstico , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/diagnóstico , Adulto , Proteínas Sanguíneas , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Valores de Referência , Índice de Gravidade de Doença , Doença de Still de Início Tardio/etiologia , Adulto Jovem
4.
J Autoimmun ; 116: 102562, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33168359

RESUMO

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10-14) and Asn in HLA-DRß1 position 37 (p = 5.12 × 10-11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10-14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10-13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10-9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.

7.
Int J Lab Hematol ; 42(2): 206-213, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958215

RESUMO

INTRODUCTION: To assess the clinical performance and correlations of automated chemiluminescence assay (CIA) and enzyme-linked immunosorbent assay (ELISA) for detecting antiphospholipid (aPL) antibodies in the diagnosis of antiphospholipid syndrome (APS). METHODS: The study recruited 505 subjects, including 192 with APS, 193 with connective tissue diseases other than APS, and 120 healthy donors. We measured anticardiolipin (aCL) and anti-ß2-glycoprotein I (anti-ß2GPI) antibodies IgG, IgM, and IgA in all the samples using both CIA and ELISA. RESULTS: Total agreement between the two methods ranged from 83.50% for anti-ß2GPI IgG antibodies to 92.76% for anti-ß2GPI IgM antibodies in all the groups. Anti-ß2GPI and aCL IgG assays showed the highest Spearman's rho coefficients (anti-ß2GPI IgG = 0.742, aCL IgG = 0.715). Anti-ß2GPI IgG CIA showed the highest sensitivity for diagnosis of APS at 80.21%, which was significantly higher than the sensitivity of anti-ß2GPI IgG ELISA (52.08%). For diagnosis of APS, anti-ß2GPI IgG CIA had the best discrimination power with the area under the curves (AUC) of 0.922, followed by aCL IgG CIA (AUC of 0.905). While the CIA AUC was slightly higher in all cases, the difference was not statistically significant. CONCLUSION: CIA measurements had a good agreement and correlation with comparative ELISA assays. The CIA anti-ß2GPI IgG however was significantly more sensitive for APS diagnosis. The two assay methodologies showed comparable predictive powers and support the value of the CIA method for improved diagnosis and management of patients with APS.


Assuntos
Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Medições Luminescentes , beta 2-Glicoproteína I/sangue , Adulto , Grupo com Ancestrais do Continente Asiático , China , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Clin Exp Rheumatol ; 37 Suppl 121(6): 52-57, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573475

RESUMO

OBJECTIVES: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis. METHODS: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses. RESULTS: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30

Assuntos
Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Doença de Still de Início Tardio , Adulto , China , Feminino , Humanos , Masculino , Indução de Remissão , Estudos Retrospectivos , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico , Doença de Still de Início Tardio/patologia , Inquéritos e Questionários
10.
Front Pharmacol ; 10: 855, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31427967

RESUMO

The burden of obesity and associated cardiometabolic diseases has been considered as an important risk factor for lupus patients. Therefore, whether obesity is involved in the over-activation of autoimmune response has attracted more and more attention. Hydroxychloroquine is a synthetic antimalarial drug and has been the clinical treatment of rheumatic diseases irreplaceable first-line drugs. Hydroxychloroquine has been suggested to have beneficial effects on lipids and insulin sensitivity, which may contribute in lowering high cardiovascular risk in SLE patients. However, its mechanism on insulin sensitivity and lipid disorders is far from being completely understood. In the present study, the therapeutic effects of hydroxychloroquine were evaluated under pathological conditions in vivo. Obesity was induced in C57BL/6 mice fed with high-fed diet, or in mice fed with high-fat diet and hydroxychloroquine. In addition, healthy mice that received normal chow diet were also monitored. The present results revealed that hydroxychloroquine reduced weight, hepatic steatosis, glucose, and insulin resistance. Furthermore, hydroxychloroquine downregulated the expression of peroxisome proliferator-activated receptor gamma in the liver. According to these present results, genes about lipid metabolism went down in high-fat mice liver. Hydroxychloroquine shows potential in ameliorating obesity-induced pathology, which acts though PPARγ to facilitate the healthy function of hepatic tissues. This evidence shows that hydroxychloroquine plays a role in improving obesity-induced lipotoxicity and insulin resistance though the peroxisome proliferator-activated receptor gamma pathway.

11.
Clin Rheumatol ; 38(1): 107-115, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30123930

RESUMO

To estimate the mortality and describe the causes of death in a large multicenter cohort of hospitalized patients with SLE in China. This was a retrospective study of a nationwide SLE cohort (10 centers, 29,510 hospitalized patients) from 2005 to 2014 in China. Standardized mortality ratios (SMRs) were calculated for all death and were stratified by sex and age. Chi-square test was used to determine whether the major causes of death vary in age, sex, duration of SLE, disease activity, or medications. Comparison between dead patients and survival controls was used to identify the risk factors for mortality. Logistic regression analysis was used to evaluate the risk factors for mortality. A total of 360 patients died during the study period, accounting for 1.22%. The overall SMR was 2.13 (95% CI 1.96, 2.30), with a particularly high SMR seen in subgroups characterized by younger age. Infection (65.8%) was the most common cause of death, followed by lupus nephritis (48.6%), hematological abnormality (18.1%), neuropsychiatric lupus/NPSLE (15.8%), and interstitial pneumonia (13.1%). Cardiovascular disease and malignancy contributed little to the causes of death. Infection, in particular severe pulmonary infection, emerged as the foremost risk factor for mortality, followed by lupus encephalopathy. However, lupus nephritis and hematological abnormalities occurred more frequently in survival patients. SLE patients at a younger age of diagnosis have a poorer prognosis. Infection dominated the causes of death in recent China. Ethnicity and medications might account for the differences in causes of death compared with western populations.


Assuntos
Causas de Morte , Lúpus Eritematoso Sistêmico/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/complicações , Criança , China/epidemiologia , Feminino , Humanos , Infecções/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Adulto Jovem
12.
Clin Chem Lab Med ; 56(4): 614-624, 2018 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-29166262

RESUMO

BACKGROUND: The aim of the study was to determine the prevalence and clinical associations of antiphosphatidylserine/prothrombin antibodies (aPS/PT) with thrombosis and pregnancy loss in Chinese patients with antiphospholipid syndrome (APS) and seronegative APS (SNAPS). METHODS: One hundred and eighty six Chinese patients with APS (67 primary, 119 secondary), 48 with SNAPS, 176 disease controls (79 systemic lupus erythematosus [SLE], 29 Sjogren's syndrome [SS], 30 ankylosing spondylitis [AS], 38 rheumatoid arthritis [RA]) and 90 healthy donors were examined. IgG and IgM aPS/PT, IgG/IgM/IgA anticardiolipin (aCL) and IgG/IgM/IgA anti-ß2-glycoprotein I (anti-ß2GPI) antibodies were tested by ELISA. RESULTS: One hundred and sixty (86.0%) of APS patients were positive for at least one aPS/PT isotype. One hundred and thirty five (72.6%) were positive for IgG aPS/PT, 124/186 (66.7%) positive for IgM aPS/PT and 99 (53.2%) positive for both. Approximately half of the SNAPS patients were positive for IgG and/or IgM aPS/PT. Highly significant associations between IgG aPS/PT and venous thrombotic events (odds ratio [OR]=6.72) and IgG/IgM aPS/PT and pregnancy loss (OR=9.44) were found. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations and those with fetal loss (p=0.014). The association between IgG/IgM aPS/PT and lupus anticoagulant (LAC) was highly significant (p<0.001). When both were positive, the OR for APS was 101.6. Notably, 91.95% (80/87) of LAC-positive specimens were positive for IgG and/or IgM aPS/PT, suggesting aPS/PT is an effective option when LAC testing is not available. CONCLUSIONS: Anti-PS/PT antibody assays demonstrated high diagnostic performance for Chinese patients with APS, detected some APS patients negative for criteria markers and may serve as potential risk predictors for venous thrombosis and obstetric complications.


Assuntos
Anticorpos Antifosfolipídeos/análise , Síndrome Antifosfolipídica/diagnóstico , Complicações do Trabalho de Parto/diagnóstico , Trombose Venosa/diagnóstico , Adulto , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/imunologia , Biomarcadores/análise , China/epidemiologia , Feminino , Humanos , Masculino , Complicações do Trabalho de Parto/epidemiologia , Complicações do Trabalho de Parto/imunologia , Fosfatidilserinas/imunologia , Valor Preditivo dos Testes , Gravidez , Protrombina/imunologia , Fatores de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/imunologia
14.
Clin Rheumatol ; 36(3): 599-608, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28130684

RESUMO

This study aims to characterize the Chinese Han patients with anti-phospholipid syndrome (APS) and compare the data with those of the Euro-Phospholipid cohort. We conducted a single center study consisting of 252 patients with definite APS from 2000 to 2015. We analyzed the clinical and laboratory characteristics of our cohort and compared the data with those of the Euro-Phospholipid cohort. Our cohort consisted of 216 females and 36 males, with a mean age at entry into this study of 41 years (range 11-74 years). Of these patients, 69 (27.4%) patients had primary APS, and 183 (72.6%) had secondary APS (SAPS), including 163 (64.7%) patients had systemic lupus erythematosus (SLE). Thrombotic events occurred in 190 (75.4%) patients, and the most common ones were deep vein thrombosis (40.1%) and stroke (23.8%), which were similar to the reports of the Euro-Phospholipid cohort. In contrast, our cohort had less pulmonary embolism (6.7%). Among 93 females with 299 pregnancy episodes, the rates of early (<10 weeks) and late fetal loss (≥10 weeks) were, respectively, 37.8% and 24.4%. The latter was significantly higher than that of the Euro-Phospholipid cohort. Moreover, 7 APS nephropathy patients (characterized histopathologically by thrombotic microangiopathy) and 8 catastrophic APS patients were found in our cohort. Anti-cardiolipin antibodies (aCL) were detected in 169 (67.1%) patients, lupus anti-coagulant (LA) was detected in 83 (32.9%), and anti-ß2 glycoprotein I antibodies (anti-ß2GPI) in 148 (58.7%) patients. These results show that some clinical manifestations of APS may vary among different racial groups.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Trombose/diagnóstico , Adolescente , Adulto , Idoso , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Grupo com Ancestrais do Continente Asiático , Criança , China , Bases de Dados Factuais , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Avaliação de Sintomas , Trombose/sangue , Trombose/complicações , Adulto Jovem
15.
J Neurol Sci ; 359(1-2): 219-25, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26671118

RESUMO

OBJECTIVE: In this study three different stimulation parameters of repetitive transcranial magnetic stimulation (rTMS) were tested to compare the efficacy of continuous theta burst stimulation (continuous TBS) for rehabilitation of unilateral spatial neglect (USN) in stroke patients. METHODS: Carefully selected cohort of thirty-eight stroke patients were randomly assigned to three treatment groups (1 Hz group, 10 Hz group and continuous TBS group) and sham group. Intervention in patients in the treatment group consisted of rTMS, while patients in the sham group received pseudo-stimulation for two weeks. All patients were administered star cancellation and line bisection tests at 4 different time points of the study. Further, all study subjects in the three treatment groups and sham group underwent diffusion-tensor imaging (DTI) at the beginning and at the end of treatment to calculate fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: Among the three stimulation parameters, star cancellation and line bisection tests revealed significant differences in outcomes at the end of treatments and one month after the end of treatments, compared to beginning of the treatments. Importantly, continuous TBS group patients displayed the best curative effect, based on behavioral scoring, at one month after end of the treatments, followed by the 1Hz group and 10 Hz group. DTI results showed a significant increase in FA and MD in superior longitudinal fasciculus, superior occipitofrontal fascicle and inferior fronto-occipital fasciculus on the left side, as well as the capsula external and inferior fronto-occipital fasciculus on the right side, in patients after continuous TBS. In addition, compared to the sham group, patients stimulated with continuous TBS exhibited a dramatic increase in FA in the left external capsule. CONCLUSION: Our study presents strong evidence that rTMS significantly improves neurocognitive functions in USN, with continuous TBS showing the best curative effect. Enhanced connections in the white matter tract network related to visual attention, as assessed by DTI, might be the potential mechanism for the observed recovery in USN using continuous TBS.


Assuntos
Lateralidade Funcional/fisiologia , Transtornos da Percepção/etiologia , Transtornos da Percepção/terapia , Acidente Vascular Cerebral/complicações , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Psicofísica , Tomógrafos Computadorizados , Resultado do Tratamento , Adulto Jovem
16.
J Neurol Sci ; 357(1-2): 157-66, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26235969

RESUMO

OBJECTIVES: In this study, we employed a rat model and examined the expression pattern of neuregulin-1 (NRG-1) in optic nerve and retinal ganglion cells (RGCs) in response to optic nerve injury to understand the role of NRG-1 in conferring protection against acute optic nerve injury. METHOD: Forty-eight male rats were randomly divided into two groups, the sham-operation group (n=24) and optic nerve injury group (n=24). Flash visual evoked potentials (FVEP) and fundography images were acquired at different time points following optic nerve injury (2h, 1d, 2d, 7d, 14d and 28d). Semi-quantitative analysis of NGR-1 expression pattern was performed by immunohistochemistry (IHC) staining. In a related experiment, 100 male rats were randomly divided into NGR-1 treatment group (n=60) (treated with increasing dose of NGR-1 at 0.5µg, 1µg and 3µg), normal saline (NS) group (n=20) and negative control group (n=20). Optic nerve injury was induced in all the animals and in situ cell death was measured by detecting the apoptosis rates using TUNEL assay. RESULTS: Fundus photography results revealed no detectable differences between the sham-operation group and optic nerve injury group at 2h, 1d, 2d and 7d. However at 2weeks, the optic discs turned pale in all animals in the optic nerve injury group. NRG-1 expression increased significantly at all time points in the optic nerve injury group (P<0.05), compared to the sham-operation group, with NRG-1 expression peaking at 14d and gradually declining by 28d. Statistically significant differences in amplitude and latency of P100 wave were also detected between the optic nerve injury and sham-operation group (P<0.05). In related experiment, compared to NS group, treatment with 1µg and 3µg of recombinant human NRG-1 resulted in statistically significant FVEP-P100 amplitude values (all P<0.05). Further, compared to the NS group, ganglion cell apoptosis was dramatically reduced in the NRG-1 group at all time points and the reduction was statistically significant in 3µg NRG-1 treatment group at 7d, 14d and 28d (all P<0.05). CONCLUSION: Our results strongly suggest that NRG-1 is highly effective in preserving normal optic nerve function and is essential for tissue repair following optic nerve injury. Thus, NRG-1 expression confers protection against acute optic nerve injury in a dose-dependent manner.


Assuntos
Modelos Animais de Doenças , Neuregulina-1/biossíntese , Fármacos Neuroprotetores , Traumatismos do Nervo Óptico/metabolismo , Traumatismos do Nervo Óptico/prevenção & controle , Animais , Humanos , Masculino , Neuregulina-1/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley
17.
Int J Clin Exp Med ; 8(1): 404-12, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25785011

RESUMO

Transplantation of neural stem cells (NSCs) in the injured spinal cord has been shown to improve functional outcome. However, the influence of NSCs transplantation on the sensory function and analgesic behaviors has not been elucidated yet. Here, we investigated whether transplanted NSCs would improve sensory function in rats subjected to complete cord transection (T10) and explore the underlying mechanism. The rats were divided into sham, SCT (spinal cord transection), and NSC implanted groups. NSCs (3 × 10(6)/ml) were implanted into injury site at the day after operation. Mechanical (the hind paw test) and thermal (the tail-flick test) were measured at 5 weeks. Immunohistochemistry and RT-PCR were used to demonstrate that expression of Brain-derived neurotrophic factor (BDNF) in the superficial of the dorsal horn. Consequently, the tail-flick latencies and paw withdrawal thresholds in NSC implanted group exhibit a significant higher than SCT group (P < 0.05). RT-PCR demonstrate that mRNA expression of BDNF was down-regulated remarkably in NSC engrafted rats. The present findings suggest that NSC transplantation inhibits neuropathic pain associated with BDNF down-regulation.

18.
PLoS One ; 7(10): e47148, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23077560

RESUMO

Kinesin motors hydrolyze ATP to produce force and do work in the cell--how the motors do this is not fully understood, but is thought to depend on the coupling of ATP hydrolysis to microtubule binding by the motor. Transmittal of conformational changes from the microtubule- to the nucleotide-binding site has been proposed to involve the central ß-sheet, which could undergo large structural changes important for force production. We show here that mutation of an invariant residue in loop L7 of the central ß-sheet of the Drosophila kinesin-14 Ncd motor alters both nucleotide and microtubule binding, although the mutated residue is not present in either site. Mutants show weak-ADP/tight-microtubule binding, instead of tight-ADP/weak-microtubule binding like wild type--they hydrolyze ATP faster than wild type, move faster in motility assays, and assemble long spindles with greatly elongated poles, which are also produced by simulations of assembly with tighter microtubule binding and faster sliding. The mutated residue acts like a mechanochemical coupling element--it transmits changes between the microtubule-binding and active sites, and can switch the state of the motor, increasing mechanical output by the motor. One possibility, based on our findings, is that movements by the residue and the loop that contains it could bend or distort the central ß-sheet, mediating free energy changes that lead to force production.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila/genética , Drosophila/metabolismo , Cinesina/genética , Cinesina/metabolismo , Microtúbulos/metabolismo , Nucleotídeos/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Domínio Catalítico , Drosophila/química , Proteínas de Drosophila/química , Cinesina/química , Modelos Moleculares , Mutação Puntual , Ligação Proteica , Estrutura Secundária de Proteína
19.
Sci Rep ; 2: 236, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22355749

RESUMO

Rotation of the coiled-coil stalk of the kinesin-14 motors is thought to drive displacements or steps by the motor along microtubules, but the structural changes that trigger stalk rotation and the nucleotide state in which it occurs are not certain. Here we report a kinesin-14 neck mutant that releases ADP more slowly than wild type and shows weaker microtubule affinity, consistent with defective stalk rotation. Unexpectedly, crystal structures show the stalk fully rotated - neck-motor interactions destabilize the stalk, causing it to rotate and ADP to be released, and alter motor affinity for microtubules. A new structural pathway accounts for the coupling of stalk rotation - the force-producing stroke - to changes in motor affinity for nucleotide and microtubules. Sequential disruption of salt bridges that stabilize the unrotated stalk could cause the stalk to initiate and complete rotation in different nucleotide states.


Assuntos
Cinesina/fisiologia , Cristalografia por Raios X , Cinesina/química , Cinesina/metabolismo , Cinética , Microtúbulos/metabolismo , Modelos Moleculares
20.
N Biotechnol ; 27(6): 789-94, 2010 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-20849992

RESUMO

A bacterium isolated from activated sludge of propylene epoxide wastewater was identified as Agrobacterium sp. M-503. It was confirmed to produce bioflocculant with excellent flocculation activity. The yield of the bioflocculant reached 14.9 g/l in batch cultivation with a carbon source conversion of 74.5%. This bioflocculant was temperature and alkaline stable, retaining almost all flocculation activity after being treated at 121°C for 20 minutes or at pH 12.0. It consisted of neutral sugar, uronic acid, aminosugar and protein in weight ratios of 85.0:9.9:2.1:3.0. The active polysaccharide fraction of the bioflocculant was purified to homogeneity by ethanol precipitation, DEAE ion-exchange and gel chromatography. Analysis of the purified polysaccharide showed that it consisted of glucose residues and had a molecular weight of 8.1 × 104 Da. Its low molecular weight endowed it with excellent solubility and favorable flocculation activity, especially for small particulates.


Assuntos
Concentração de Íons de Hidrogênio , Polissacarídeos/isolamento & purificação , Rhizobium/metabolismo , Esgotos/microbiologia , Temperatura , Floculação , Peso Molecular , Tamanho da Partícula , Polissacarídeos/química , Rhizobium/química
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