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1.
Biochem Biophys Res Commun ; 521(1): 42-49, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629475

RESUMO

In our previous study, Oxysterol-binding protein-related protein 2 (OSBPL2) was first identified as a new deafness-causative gene contribute to non-syndromic hearing loss. However, the underlying mechanism of OSBPL2-induced hearing loss remains unknown. Here, we used hearing-specific cells and tissues OC-1 cells and zebrafish inner ear tissues as models to identify common transcriptome changes in genes and pathways in the absence of human OSBPL2 orthologues by RNA-seq analysis. In total, 2112 differentially expressed genes (DEGs) were identified between wild-type (WT) and Osbpl2-/- OC-1 cells, and 877 DEGs were identified between WT and osbpl2b-/- zebrafish inner ear tissues. Functional annotation implicated Osbpl2/osbpl2b in lipid metabolism, cell adhesion and the extracellular matrix in both OC-1 cells and zebrafish inner ear tissues. Protein-protein interaction (PPI) analysis indicated that Osbpl2/osbpl2b were also involved in ubiquitination. Further experiments showed that Osbpl2-/- OC-1 cells exhibited an abnormal focal adhesion morphology characterized by inhibited FAK activity and impaired cell adhesion. In conclusion, we identified novel pathways modulated by OSBPL2 orthologues, providing new insight into the mechanism of hearing loss induced by OSBPL2 deficiency.

2.
Med Sci Monit ; 25: 9702-9711, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31851643

RESUMO

BACKGROUND This study was to investigate the correlation between osteoporosis and serum uric acid in ankylosing spondylitis (AS) patients, and to further identify potential factors that might be associated with osteoporosis in AS patients. MATERIAL AND METHODS We included 182 AS patients, consisted of 143 male patients and 39 female patients, who visited our hospital from January 1, 2014 to December 31, 2018. We used dual-energy x-ray absorptiometry to measure bone mineral density (BMD) of orthotopic lumbar vertebrae in patients with AS. The gender, age, disease duration, BMD, T-score, Z-score, uric acid, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood platelet (PLT), and status of treatment with biologics of the patients were collected. Then, the Spearman correlation coefficient and multivariate liner regression analysis were applied to identify the relationship between the factors and BMD, T-score, and Z-score in AS patients. RESULTS Male AS patients between the ages of 16 and 30 years old had a higher risk of osteoporosis (P<0.05). AS patients with uric acid value between 300-360 µmol/L had the highest BMD, T-score, and Z-score. The BMD had a positive correlation with age and disease duration (P<0.01) while had a negative correlation with PLT (P<0.05). BMD in AS patients with elevated ESR was significantly (P<0.05) lower than in AS patients with normal ESR. There were no significant differences in BMD between AS patients with elevated CRP and the patients with normal CRP and PLT. Treatment with TNFi (tumor necrosis factor alpha inhibitor) did not improve BMD in AS patients. CONCLUSIONS The relationship between uric acid and BMD in AS patients was observed as inverted "U"-type. Keeping uric acid within 300-360 µmol/L might be helpful in preventing AS patients from developing osteoporosis.


Assuntos
Grupo com Ancestrais do Continente Asiático , Osteoporose/sangue , Osteoporose/complicações , Espondilite Anquilosante/sangue , Espondilite Anquilosante/complicações , Ácido Úrico/sangue , Adolescente , Adulto , Antirreumáticos/uso terapêutico , Plaquetas/metabolismo , Sedimentação Sanguínea , Densidade Óssea , Proteína C-Reativa/metabolismo , Feminino , Humanos , Inflamação/sangue , Inflamação/patologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/fisiopatologia , Adulto Jovem
3.
Cell Death Dis ; 10(9): 627, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427568

RESUMO

Oxysterol-binding protein like 2 (OSBPL2) was identified as a novel causal gene for autosomal dominant nonsyndromic hearing loss. However, the pathogenesis of OSBPL2 deficits in ADNSHL was still unclear. The function of OSBPL2 as a lipid-sensing regulator in multiple cellular processes suggested that OSBPL2 might play an important role in the regulation of cholesterol-homeostasis, which was essential for inner ear. In this study the potential roles of OSBPL2 in cholesterol biosynthesis and ROS production were investigated in Osbpl2-KO OC1 cells and osbpl2b-KO zebrafish. RNA-seq-based analysis suggested that OSBPL2 was implicated in cholesterol biosynthesis and AMPK signaling pathway. Furthermore, Osbpl2/osbpl2b-KO resulted in a reduction of AMPK activity and up-regulation of Srebp2/srebp2, Hmgcr/hmgcr and Hmgcs1/hmgcs1, key genes in the sterol biosynthetic pathway and associated with AMPK signaling. In addition, OSBPL2 was also found to interact with ATIC, key activator of AMPK. The levels of total cholesterol and ROS in OC1 cells or zebrafish inner ear were both increased in Osbpl2/osbpl2b-KO mutants and the mitochondrial damage was detected in Osbpl2-KO OC1 cells. This study uncovered the regulatory roles of OSBPL2 in cellular cholesterol biosynthesis and ROS production. These founds might contribute to the deep understanding of the pathogenesis of OSBPL2 mutation in ADNSHL.

4.
Exp Cell Res ; 383(2): 111512, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31356817

RESUMO

Previous studies have shown that oxysterol binding protein like 2 (OSBPL2) knockdown is closely related to cholesterol metabolism. However, whether there is a direct relation between OSBPL2 and cholesterol synthesis is unknown. This study explored the mechanism of OSBPL2 deficiency in the upregulation of squalene epoxidase (SQLE) and the subsequent accumulation of intracellular cholesterol and cholesteryl ester. Here, we constructed an OSBPL2-deleted HeLa cell line using CRISPR/Cas9 technology, screened differentially expressed genes and examined the transcriptional regulation of SQLE using a dual-luciferase reporter gene. RNA-seq analysis showed that SQLE was upregulated significantly and the dual luciferase reporter gene assay revealed that two new functional transcription factor binding sites of Sp1 transcription factor (SP1) and sterol regulatory element-binding transcription factor 2 (SREBF2) in the SQLE promoter participated in the SQLE transcription and expression. In addition, we also observed that OSBPL2 deletion inhibited the AMPK signalling pathway and that the inhibition of AMPK signalling promoted SP1 and SREBF2 entry into the nuclear to upregulate SQLE expression. Therefore, these data support that OSBPL2 deficiency upregulates SQLE expression and increases the accumulation of cholesterol and cholesteryl ester by suppressing AMPK signalling, which provides new evidence of the connection between OSBPL2 and cholesterol synthesis.

5.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(2): 222-224, 2019 Feb 28.
Artigo em Chinês | MEDLINE | ID: mdl-30837393

RESUMO

Nivolumab is an anti-programmed cell death (anti-PD-1) monoclonal antibody, which is a new drug for tumor immunotherapy. A 73-year-old female patient with colorectal cancer 3 years after surgery was treated in the Endocrinology Department of Third Xiangya Hospital, Central South University, who developed severe hypothyroidism resulting from treatment with nivolumab. After 4 months treatment of nivolumab, this patient presented with symptoms such as fatigue, dizziness, jaundice and palpebral edema, with decreased levels of FT3 and FT4 and elevated levels of TSH. Subsequently, nivolumab treatment was terminated. This patient's symptoms were relieved and thyroid function returned to normal after thyroxine replacement therapy. The clinical diagnosis was considered to be nivolumab-induced autoimmune thyroid damage, which was an immune-related adverse reaction in the treatment.


Assuntos
Hipotireoidismo , Nivolumabe/efeitos adversos , Idoso , Anticorpos Monoclonais , Feminino , Humanos , Hipotireoidismo/induzido quimicamente , Tiroxina
6.
J Steroid Biochem Mol Biol ; 187: 17-26, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30391516

RESUMO

Oxysterol Binding Protein Like 2 (OSBPL2) is a lipid-binding protein implicated in various cellular processes. Previous studies have shown that depression of OSBPL2 significantly increases the level of cellular 25-hydroxycholesterol (25-OHC) which regulates the expression of lipid-metabolism-related genes. However, whether 25-OHC can regulate the expression of OSBPL2 remains unanswered. This study aimed to explore the molecular mechanism of 25-OHC regulating the expression of OSBPL2. Using dual-luciferase reporter assay, we found a decrease of nuclear transcription factor Y subunit alpha (NFYA) bound with OSBPL2 promoter when HeLa cells were treated with 25-OHC. Furthermore, transcriptome sequencing and RNA interference results revealed that the p53/sterol regulatory element binding transcription factor 2 (SREBF2) signaling pathway was involved in the NFYA-dependent transcription of OSBPL2 induced by 25-OHC. Based on these results, we concluded that pleomorphic adenoma gene 1 (PLAG1) and NFYA participated in the basal transcription of OSBPL2 and that 25-OHC decreased the transcription of OSBPL2 via the p53/SREBF2/NFYA signaling pathway. 25-OHC will accumulate over time in OSBPL2 knockdown cells. These results may provide a new insight into the deafness caused by OSBPL2 mutation.


Assuntos
Fator de Ligação a CCAAT/metabolismo , Regulação para Baixo , Hidroxicolesteróis/metabolismo , Receptores de Esteroides/genética , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Células HeLa , Humanos , Regiões Promotoras Genéticas
7.
Int Immunopharmacol ; 67: 186-193, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30553912

RESUMO

The aggressive phenotype displayed by fibroblast-like synoviocytes (FLSs) contributes to cartilage and bone destruction in rheumatoid arthritis (RA). Betulinic acid has been demonstrated to have a positive therapeutic effect on tumor, inflammation and immune disorder, however, the effects of betulinic acid on RA FLSs have not been verified. Therefore, in the present study, we observed the effect of betulinic acid on the migration and invasion of RA FLSs and explored its underlying signal mechanisms. Our results showed that betulinic acid treatment suppressed the migration, invasion and reorganization of the actin cytoskeleton of RA FLSs. In addition, we found that the mRNA expression of IL-1ß, IL-6, IL-8 and IL-17A were markedly down-regulated by treatment with betulinic acid in TNF-α-induced RA FLSs. To gain insight into the molecular mechanisms, we evaluated the effect of betulinic acid on NF-κB activation in RA FLSs. The results indicated that betulinic acid treatment reduced the TNF-α-induced activation of NF-κB signal pathway and the NF-κB nuclear accumulation. We also observed that treatment with betulinic acid attenuated synovial inflammation and joint destruction in mice with CIA. Taken together, these results suggest that betulinic acid inhibits the migration and invasion of RA FLSs by blocking NF-κB signal pathway activation.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Sinoviócitos/efeitos dos fármacos , Triterpenos/uso terapêutico , Adulto , Idoso , Animais , Movimento Celular , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fibroblastos/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Transdução de Sinais , Sinoviócitos/fisiologia
8.
Ann Clin Lab Sci ; 48(4): 435-439, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30143483

RESUMO

BACKGROUND AND AIM: Gout is an inflammatory disease affecting multiple joints. Abnormal coagulation can elevate the levels of plasma D-dimer (DD) and is associated with inflammation and joint-related disease activity. Patients with gout usually develop acute gouty attack. However, there is no information on whether abnormal levels of plasma DD are associated with a gout flare. This study examined the levels of blood C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum uric acid (UA) and plasma DD in patients with gout flare and those with gout in remission phase and evaluated their value in predicting a gout flare as well as in the treatment of gout flare. METHODS: The levels of serum UA, plasma DD and blood CRP as well as blood ESR in 50 patients with gout flare and 27 patients with gout in remission phase were determined. The data were stratified and their potential values in predicting the onset of gout flare were analyzed by receiver-operating characteristic (ROC) analysis. RESULTS: The levels of DD, CRP and ESR in patients with gout flare were significantly higher than that in patients with gout in remission. The ROC analysis indicated that the area under curve (AUC) of DD, ESR as well as CRP were 0.914 (95% CI: 0.909~1.001, p<0.05), 0.956 (95%CI: 0.917~0.994, p<0.05), and 0.942 (95%CI: 0.894~0.989, p<0.05), respectively. The current study revealed that sensitivity of plasma DD concentration in predicting gout attack was significantly higher than that of blood ESR (p<0.05). CONCLUSION: Plasma DD may be a sensitive biomarker in predicting the onset of gout flare, but more importantly, it might serve as an indicator of treatment for the dysfunction of blood coagulation in gout patients.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Gota/sangue , Gota/terapia , Doença Aguda , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Feminino , Gota/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Ácido Úrico/sangue
9.
J Assist Reprod Genet ; 35(5): 913-919, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29476300

RESUMO

PURPOSE: The purpose of this study was to investigate a novel mutation in the luteinizing hormone beta-subunit (LHB) gene in one male patient with hypogonadism due to selective luteinizing hormone (LH) deficiency. METHODS: Sanger sequencing of one 28-year-old man born to consanguineous parents was performed. Treatment with human chorionic gonadotropin (hCG) (2000 IU, twice a week) was initiated for 3 months, followed by 5000 IU weekly to date. RESULTS: We identified a novel c.84G>A[p.W28X] nonsense LHB mutation. The W28X mutation produces a truncated LHB peptide of seven amino acids, which prevents the synthesis of intact LH. After 40 days of treatment with hCG, the patient exhibited a few spermatozoa in the semen. Treated for 6 months, the patient exhibited normal seminal parameters. CONCLUSIONS: We identified a novel mutation in the LHB gene in a male patient with hypogonadism and provided evidence that LHB nonsense mutation can cause selective LH deficiency. We reconfirmed hCG treatment may restore male fertility due to LHB mutation.


Assuntos
Códon sem Sentido , Hipogonadismo/genética , Hormônio Luteinizante Subunidade beta/genética , Hormônio Luteinizante/deficiência , Adulto , Gonadotropina Coriônica/uso terapêutico , Feminino , Homozigoto , Humanos , Hipogonadismo/tratamento farmacológico , Hormônio Luteinizante/genética , Masculino , Linhagem
10.
Int Immunopharmacol ; 55: 174-182, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29268189

RESUMO

In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) play an essential role in cartilage destruction. Aggressive migration and invasion by FLSs significantly affect RA pathology. Kaempferol has been shown to inhibit cancer cell migration and invasion. However, the effects of kaempferol on RA FLSs have not been investigated. Our study aimed to determine the effects of kaempferol on RA both in vitro and in vivo. In vitro, cell migration and invasion were measured using scratch assays and the Boyden chamber method, respectively. The cytoskeletal reorganization of RA FLSs was evaluated by immunofluorescence staining. Matrix metalloproteinase (MMP) levels were measured by real-time PCR, and protein expression levels were measured by western blotting. In vivo, the effects of kaempferol were evaluated in mice with CIA. The results showed that kaempferol reduced migration, invasion and MMP expression in RA FLSs. In addition, we demonstrated that kaempferol inhibited reorganization of the actin cytoskeleton during cell migration. Moreover, kaempferol dramatically suppressed tumor necrosis factor (TNF)-α-induced MAPK activation without affecting the expression of TNF-α receptors. We also demonstrated that kaempferol attenuated the severity of arthritis in mice with CIA. Taken together, these results suggested that kaempferol inhibits the migration and invasion of FLSs in RA by blocking MAPK pathway activation without affecting the expression of TNF-α receptors.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/fisiologia , Quempferóis/uso terapêutico , Sinoviócitos/fisiologia , Actinas/metabolismo , Adulto , Idoso , Animais , Artrite Experimental , Movimento Celular , Células Cultivadas , Citoesqueleto/metabolismo , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo
11.
Mol Med Rep ; 16(5): 5931-5937, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28849214

RESUMO

G protein­coupled receptor­associated sorting protein 2 (GPRASP2), a member of the GASP family, has been reported to be involved in the modulation of transcription. However, few studies have revealed the role of GPRASP2 in the development and progression of diseases. As a model organism, zebrafish have been widely used to investigate human diseases. In the present study, zebrafish armadillo repeat­containing 10 (armc10), an orthologous gene of human GPRASP2 was identified, and the spatial and temporal expression patterns of armc10 in zebrafish during early embryonic development were revealed. Bioinformatics analyses showed that ARMC10 protein sequences were highly conserved. Reverse transcription polymerase chain reaction analysis and whole mount in situ hybridization revealed that zebrafish armc10 was maternally expressed and was detected at a weak level up to 12 h post­fertilization (hpf), however, its expression increased to a high level at 24 hpf. At the 75% epiboly stage and 12 hpf, armc10 was widely expressed in the embryo. At 24 hpf, armc10 mRNA was expressed in the nervous system of the zebrafish head. When the embryo was 2 days old, the wide expression of armc10 was maintained in the nervous system of the zebrafish head. At 72 hpf, the mRNA expression of armc10 was located specifically in the otic vesicles in addition to the nervous system of the head. At 96 hpf, the expression of armc10 was maintained in the otic vesicles and the nervous system of the head. The results of the present study provided novel insight into the spatial and temporal mRNA expression of armc10 in zebrafish, for the further investigation of nervous system diseases.


Assuntos
Proteínas do Domínio Armadillo/genética , Proteínas de Transporte/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/genética , Proteínas de Peixe-Zebra/genética , Sequência de Aminoácidos , Animais , Proteínas do Domínio Armadillo/metabolismo , Proteínas de Transporte/metabolismo , Sequência Conservada , Embrião não Mamífero , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas do Tecido Nervoso/metabolismo , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
12.
Rheumatology (Oxford) ; 56(8): 1417-1427, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28431044

RESUMO

Objective: To explore the role of leonurine in the regulation of synovial inflammation and joint destruction inRA. Methods: Fibroblast-like synoviocytes were isolated from synovial tissue from RA patients. Pro-inflammatory cytokine and MMP expression was evaluated using real-time PCR and a cytometric bead array. Cell migration and invasion in vitro were measured using the Boyden chamber method and the scratch assay, respectively. Protein expression was measured by western blotting. Nuclear factor kappa B (NF-κB) nuclear translocation was detected by immunofluorescence. The in vivo effect of leonurine was evaluated in mice with CIA. Results: Leonurine treatment significantly decreased the production of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8 and TNFα) and MMPs (MMP-1 and MMP-3) and suppressed the migration and invasion of RA fibroblast-like synoviocytes. The molecular analysis revealed that leonurine impaired TNFα-induced NF-κB signalling by inhibiting the phosphorylation and degradation of inhibitor of NF-κB alpha (IκBα) and subsequently preventing the nuclear translocation of the NF-κB p65 subunit. Leonurine also inhibited the p38 and Jun N-terminal kinase mitogen-activated protein kinases signalling pathways without affecting ERK signalling. Intraperitoneal injection of leonurine reduced synovial inflammation, joint destruction and the serum IL-1ß, IL-6 and TNFα levels in mice with CIA. Conclusion: Our findings show that leonurine reduces synovial inflammation and joint destruction in RA through the NF-κB and mitogen-activated protein kinases pathways. Leonurine has potential as a therapeutic agent for RA.


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Ácido Gálico/análogos & derivados , Adulto , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Citocinas/efeitos dos fármacos , Feminino , Fibroblastos/metabolismo , Ácido Gálico/farmacocinética , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Metaloproteinase 1 da Matriz/efeitos dos fármacos , Metaloproteinase 3 da Matriz/efeitos dos fármacos , Camundongos , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/patologia , Fator de Transcrição RelA/efeitos dos fármacos
13.
Clin Rheumatol ; 36(1): 35-43, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27709444

RESUMO

The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (≥18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 ± 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including Enbrel® and local brand Yi Sai Pu® and Qiangke®), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 ± 15.6 mg for 25.5 ± 47.0 weeks and tocilizumab at 94.5 ± 21.9 mg for 4.7 ± 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for <3 months, those receiving bDMARDs for ≥3 months exhibited significantly lower DAS28 scores (p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for ≥12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Adalimumab/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , China , Estudos Transversais , Etanercepte/administração & dosagem , Feminino , Humanos , Infliximab/administração & dosagem , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Tamanho da Amostra , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
14.
Exp Ther Med ; 11(3): 1027-1030, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26998032

RESUMO

The present study reported high levels of D-dimer associated with multiple joint pain in a 5-year-old patient with systemic juvenile idiopathic arthritis (JIA). While treatment with methotrexate (MTX), hydroxychloroquine and methylprednisolone was found to reduce the D-dimer level and alleviated joint pain, the fever was not effectively controlled. Addition of etanercept to the treatment regimen from week 2 resulted in a clinical remission. Following 4-6 months of therapy, the D-dimer level of the patient returned to the normal range, and symptoms of noticeable joint pain and fever were absent. A literature search showed that the levels of D-dimer may be associated with JIA disease severity, and can serve as a prognostic biomarker for JIA treatment. In conclusion, the present study demonstrated that, while MTX therapy effectively reduced D-dimer levels, addition of etanercept to the treatment regimen was required to achieve a long-lasting remission of clinical symptoms, including fever.

15.
Artigo em Inglês | MEDLINE | ID: mdl-26346320

RESUMO

To explore the effects of traditional Chinese medicine constitution (TCMC) on transformation of good health status to suboptimal health status (SHS), we conducted a nested case-control study among college students in China. During the 18-month mean follow-up time, 543 cases of SHS (42.7%) occurred in 1273 healthy students. There was a significant (P = 0.000) and marked reduction in SHMS V1.0 total score in the case group at the 18-month follow-up (69.32 ± 5.45) compared with baseline (78.60 ± 4.70), but there was no significant change in the control group. Conditional logistic regression analysis showed that respondents reporting Yin-deficiency and Qi-deficiency were, respectively, 2.247 and 2.198 times more likely to develop SHS, while tendency to Yin-deficiency and tendency to Damp-heat were, respectively, 1.642 and 1.506 times more likely to develop SHS. However, the Balanced Constitution was a significant protective factor (OR 0.649; P < 0.05). Altogether, these findings demonstrate that Yin-deficiency, Qi-deficiency, tendency to Yin-deficiency, and tendency to Damp-heat appeared to induce a change in health status to SHS, while the Balanced Constitution seemed to restrain this change. We conclude that regulating the unbalanced TCMC (such as Yin-deficiency and Qi-deficiency) may prevent a healthy status developing into SHS or lead to the regression of SHS.

16.
J Biol Chem ; 288(41): 29403-13, 2013 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-23996002

RESUMO

PKA signaling is important for the post-translational modification of proteins, especially those in cardiomyocytes involved in cardiac excitation-contraction coupling. PKA activity is spatially and temporally regulated through compartmentalization by protein kinase A anchoring proteins. Cypher/ZASP, a member of PDZ-LIM domain protein family, is a cytoskeletal protein that forms multiprotein complexes at sarcomeric Z-lines. It has been demonstrated that Cypher/ZASP plays a pivotal structural role in the structural integrity of sarcomeres, and several of its mutations are associated with myopathies including dilated cardiomyopathy. Here we show that Cypher/ZASP, interacting specifically with the type II regulatory subunit RIIα of PKA, acted as a typical protein kinase A anchoring protein in cardiomyocytes. In addition, we show that Cypher/ZASP itself was phosphorylated at Ser(265) and Ser(296) by PKA. Furthermore, the PDZ domain of Cypher/ZASP interacted with the L-type calcium channel through its C-terminal PDZ binding motif. Expression of Cypher/ZASP facilitated PKA-mediated phosphorylation of the L-type calcium channel in vitro. Additionally, the phosphorylation of the L-type calcium channel at Ser(1928) induced by isoproterenol was impaired in neonatal Cypher/ZASP-null cardiomyocytes. Moreover, Cypher/ZASP interacted with the Ser/Thr phosphatase calcineurin, which is a phosphatase for the L-type calcium channel. Taken together, our data strongly suggest that Cypher/ZASP not only plays a structural role for the sarcomeric integrity, but is also an important sarcomeric signaling scaffold in regulating the phosphorylation of channels or contractile proteins.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Canais de Cálcio Tipo L/metabolismo , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Proteínas com Domínio LIM/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Animais Recém-Nascidos , Células Cultivadas , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/química , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Células HEK293 , Humanos , Immunoblotting , Proteínas com Domínio LIM/química , Proteínas com Domínio LIM/genética , Camundongos , Camundongos Knockout , Modelos Moleculares , Mutação , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Domínios PDZ/genética , Fosforilação , Ligação Proteica , Ratos , Sarcômeros/metabolismo , Serina/química , Serina/genética , Serina/metabolismo
17.
Hum Mutat ; 32(12): 1335-40, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21901790

RESUMO

The Human Variome Project (HVP) is an international consortium of clinicians, geneticists, and researchers from over 30 countries, aiming to facilitate the establishment and maintenance of standards, systems, and infrastructure for the worldwide collection and sharing of all genetic variations effecting human disease. The HVP-China Node will build new and supplement existing databases of genetic diseases. As the first effort, we have created a novel variant database of BRCA1 and BRCA2, mismatch repair genes (MMR), and APC genes for breast cancer, Lynch syndrome, and familial adenomatous polyposis (FAP), respectively, in the Chinese population using the Leiden Open Variation Database (LOVD) format. We searched PubMed and some Chinese search engines to collect all the variants of these genes in the Chinese population that have already been detected and reported. There are some differences in the gene variants between the Chinese population and that of other ethnicities. The database is available online at http://www.genomed.org/LOVD/. Our database will appear to users who survey other LOVD databases (e.g., by Google search, or by NCBI GeneTests search). Remote submissions are accepted, and the information is updated monthly.


Assuntos
Polipose Adenomatosa do Colo/genética , Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Bases de Dados Genéticas , Predisposição Genética para Doença , China , Reparo de Erro de Pareamento de DNA/genética , Feminino , Genes APC , Genes BRCA1 , Genes BRCA2 , Variação Genética , Humanos
18.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 31(6): 769-74, 2011 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-21823421

RESUMO

OBJECTIVE: To assess the therapeutic efficacy and safety of Kunxian Capsule (KXC) in treatment of rheumatoid arthritis (RA). METHODS: Randomized positive parallel controlled and multi-center open test method was adopted. 240 RA patients of mild/moderate degree were randomly assigned to three groups equally, i.e., KXC group (who took KXC), the methotrexate (MTX) group (who took MTX), and the KXC + MTX group (who took KXC and MTX simultaneously), respectively. The therapeutic course for them all was 12 weeks. The effect of the treatment was assessed in items of DAS28, ACR20, and ACR50; number of joints with pain and swelling; VAS score of pain, tiredness, and general condition; time of morning stiffness; bilateral grip strength; HAQ score, as well as blood levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP antibody, and platelet count. RESULTS: By the end of the 4th week, the improvement of ACR20, ACR50, DAS28 efficacy judgment, and DAS28 score in the KXC + MTX group were much better than those in the other two groups, with statistical difference (P<0.05). The total effective rate was 88. 6% and the markedly effective rate was 51.8% in the KXC + MTX group at the 12 th week. The Improvement was more obviously shown in all groups after treatment (all P<0.05). Better effects in reducing VAS scores of pain and tiredness were shown in the KXC group and the KXC + MTX group. The effects of KXC + MTX were superior to the other two groups in terms of swollen joint numbers, pain joints, grip strength (assessed by researcher), as well as VAS score of general condition and HAQ score (assessed by both patients and researcher, P<0.05). But the differences among groups in improving morning stiffness and the incidence rate of adverse events were in- significant. CONCLUSIONS: KXC could relieve symptoms, improve joint functions, physical signs, and laboratory indices of RA patients with less adverse reaction. It was synergistic with MTX.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Adulto , Antirreumáticos/uso terapêutico , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Hum Mutat ; 31(11): E1801-10, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20809527

RESUMO

The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders that predisposes young individuals to ventricular arrhythmias and sudden death. LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion channels (KCNQ1, KCNH2,SCN5A, KCNE1, and KCNE2). Many other genes involved in LQTS have been described recently(KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and CAV3). We created an online database(http://www.genomed.org/LOVD/introduction.html) that provides information on variants in LQTS-associated genes. As of February 2010, the database contains 1738 unique variants in 12 genes. A total of 950 variants are considered pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292 have no known pathogenicity. In addition to these mutations collected from published literature, we also submitted information on gene variants, including one possible novel pathogenic mutation in the KCNH2 splice site found in ten Chinese families with documented arrhythmias. The remote user is able to search the data and is encouraged to submit new mutations into the database. The LQTS database will become a powerful tool for both researchers and clinicians.


Assuntos
Bases de Dados Genéticas , Síndrome do QT Longo/genética , Mutação , Predisposição Genética para Doença , Variação Genética , Humanos , Internet , Canais Iônicos/genética , Síndrome do QT Longo/classificação
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