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1.
J Clin Lab Anal ; 36(4): e24270, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35274367

RESUMO

BACKGROUND: Jun N-terminal kinase pathway-associated phosphatase (JKAP) regulates neuronal function, T helper (Th) 1/2/17 cell differentiation, and inflammatory process, but its clinical role in acute ischemic stroke (AIS) patients remains unclear. Hence, this study intended to evaluate JKAP level and its relationship with disease severity, Th1, 2, 17 secreted cytokines, adhesion molecules, and prognosis of AIS patients. METHODS: Serum JKAP of 122 AIS patients and 50 controls was detected by ELISA. For AIS patients only, Th1, 2, 17 secreted cytokines IFN-γ, IL-4, IL-17; TNF-α, ICAM-1, and VCAM-1 were also detected by ELISA. RESULTS: JKAP was decreased in AIS patients compared with controls (46.350 (interquartile range (IQR): 34.250-59.875) pg/ml vs. 84.500 (IQR: 63.175-113.275) pg/ml, p < 0.001), which could distinguish AIS patients from controls (area under curve (AUC): 0.810, 95% confidence interval (CI): 0.732-0.888). In AIS patients, JKAP negatively linked with the National Institutes of Health Stroke Scale (NIHSS) score (rs  = -0.342, p < 0.001); besides, it was positively related to IL-4 (rs  = 0.213, p = 0.018) and negatively associated with IL-17 (rs  = -0.270, p = 0.003) but not related to IFN-γ (rs  = -0.146, p = 0.109). Furthermore, elevated JKAP associated with declined TNF-α (rs  = -0.219, p = 0.015) and ICAM-1 (rs  = -0.235, p = 0.009) but not related to VCAM-1 (rs  = -0.156, p = 0.085). Besides, declined JKAP was linked with 2-year recurrence (p = 0.027) and 3-year recurrence (p = 0.010) in AIS patients; while JKAP was not related to 1-year recurrence or death risk (both p > 0.050). CONCLUSION: JKAP may sever as a candidate prognostic biomarker in AIS patients, indicating its potency for AIS management.


Assuntos
Isquemia Encefálica , Fosfatases de Especificidade Dupla/sangue , AVC Isquêmico , Fosfatases da Proteína Quinase Ativada por Mitógeno/sangue , Acidente Vascular Cerebral , Citocinas , Humanos , Molécula 1 de Adesão Intercelular , Interleucina-17 , Interleucina-4 , Fator de Necrose Tumoral alfa , Molécula 1 de Adesão de Célula Vascular
2.
J Clin Lab Anal ; 36(2): e24199, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34973040

RESUMO

BACKGROUND: Dual specificity phosphatase 22 (DUSP22) plays an important role in the regulation of immune and inflammation, but its correlation with clinical features and treatment outcome in psoriasis patients is still unclear. This study was to investigate the longitudinal change of DUSP22 with time, as well as its association with disease activity and treatment response in psoriasis patients. METHODS: Totally, 120 psoriasis patients, 50 patients with other skin inflammations as disease controls (DCs), and 50 health controls (HCs) were recruited. Serum samples were collected from psoriasis patients at baseline, month (M)1, M3, and M6 after initiation of etanercept-based treatment as well as from DCs and HCs after enrollment to assess DUSP22 level by enzyme-linked immunosorbent assay. RESULTS: DUSP22 was lower in psoriasis patients than in HCs and DCs (both p < 0.001). Besides, in psoriasis patients, DUSP22 was associated with lower psoriasis area severity index (PASI) score (p = 0.001) and systemic biological treatment history (p = 0.023), but not with other demographics, disease characteristics, or treatment history (all p>0.05). In addition, DUSP22 was increased with time (p < 0.001) in total patients. Moreover, DUSP22 at M3 (p = 0.004) and M6 (p < 0.001) was higher in response patients than in non-response patients evaluated by PASI 75. Additionally, DUSP22 at M3 (p < 0.001) and M6 (p = 0.003) was also increased in response patients compared with non-response patients evaluated by PASI 90. CONCLUSION: DUSP22 decreases and negatively correlates with disease activity, while its longitudinal elevation with time reflects satisfactory treatment response in psoriasis patients.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Fosfatases de Especificidade Dupla/sangue , Etanercepte/uso terapêutico , Fosfatases da Proteína Quinase Ativada por Mitógeno/sangue , Psoríase/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
3.
J Clin Lab Anal ; 36(1): e24111, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34811816

RESUMO

BACKGROUND: Dual specificity phosphatase 22 (DUSP22), also named as Jun N-terminal kinase pathway associated phosphatase recently, is reported to be closely engaged in immune and inflammation regulation. This study aimed to investigate the interaction between synovium DUSP22 and serum DUSP22 levels and to explore their correlation with rheumatoid arthritis (RA) risk, inflammation, and disease activity. METHODS: Synovium and serum samples from 42 RA patients with knee involvement underwent arthroscopy, and 20 knee trauma patients were collected. Besides, serum samples from 40 healthy controls were also obtained. Synovium DUSP22 expression was detected by reverse transcription quantitative polymerase chain reaction, while serum DUSP22 level was detected by enzyme-linked immunosorbent assay. RESULTS: Synovium DUSP22 level was greatly decreased in RA patients compared to trauma controls (p < 0.001), and it was negatively correlated with tender joint count (TJC) (r = -0.318, p = 0.040), C-reactive protein (CRP) (r = -0.330, p = 0.033), and Lysholm score (r = -0.423, p = 0.005) in RA patients. Serum DUSP22 level was lowest in RA patients, followed by trauma controls, then highest in healthy controls (p < 0.001). Serum DUSP22 level was negatively associated with TJC (r = -0.438, p = 0.004), swollen joint count (SJC) (r = -0.372, p = 0.015), CRP (r = -0.391, p = 0.011), and disease activity score in 28 joints (DAS28ESR ) score (r = -0.406, p = 0.008), and it increased after treatment (p = 0.001) in RA patients. In addition, serum DUSP22 level positively related to synovium DUSP22 level in RA patients (r = 0.394, p = 0.010). CONCLUSION: Synovium and serum DUSP22 are intercorrelated and insufficiently expressed in RA patients; meanwhile, their deficiency correlates with increased systemic inflammation, disease activity, and joint dysfunction.


Assuntos
Artrite Reumatoide , Fosfatases de Especificidade Dupla/análise , Fosfatases da Proteína Quinase Ativada por Mitógeno/análise , Membrana Sinovial/química , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/metabolismo , Biomarcadores/análise , Biomarcadores/sangue , Fosfatases de Especificidade Dupla/sangue , Fosfatases de Especificidade Dupla/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatases da Proteína Quinase Ativada por Mitógeno/sangue , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo
4.
Ann Clin Transl Neurol ; 8(9): 1786-1795, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34289265

RESUMO

OBJECTIVE: JNK pathway-associated phosphatase (JKAP) is previously reported to regulate immune/inflammatory process via T-cell signaling, and closely involves in neurological diseases, while its implication in Parkinson's disease (PD) is unknown. Therefore, this study aimed to investigate the correlation of JKAP with Th1/Th2/Th17 cells and their clinical roles in PD patients, and then further explore the effect of JKAP on regulating CD4+ T-cell differentiation in PD. METHODS: Totally 50 PD patients and 50 age-/gender-matched controls were enrolled. Their blood samples were collected and proposed to ELISA and flow cytometry assays for JKAP, Th1, Th2, and Th17 measurements. In vitro, CD4+ T cells were isolated from PD patients then transfected with JKAP overexpression and knockdown Lentivirus, followed by detection of markers (CD25+ cell proportion, CD69+ cell proportion, IFN-γ, IL10, and IL17). RESULTS: JKAP was downregulated in PD patients compared to controls, which also showed good potency to discriminate them. Besides, JKAP negatively correlated with Th1 and Th17 cell proportions, but did not associate with Th2 cell proportion in PD patients; Interestingly, JKAP did not correlated with Th1, Th2, or Th17 cell proportions in controls. Furthermore, JKAP correlated with some parts of unified Parkinson's Disease Rating Scale (UPDRS) and Mini-Mental State Examination (MMSE) score. In vitro, JKAP overexpression repressed CD4+ T-cell activation and its differentiation into Th1 and Th17 cells in PD, while JKAP knockdown appeared opposite effect. INTERPRETATION: JKAP associates with disease risk and severity, correlates with Th1 and Th17 cells, and regulates CD4+ T-cell activation/differentiation in PD.


Assuntos
Fosfatases de Especificidade Dupla/sangue , Fosfatases da Proteína Quinase Ativada por Mitógeno/sangue , Doença de Parkinson/sangue , Doença de Parkinson/fisiopatologia , Células Th1 , Células Th17 , Idoso , Linfócitos T CD4-Positivos , Diferenciação Celular/fisiologia , Regulação para Baixo , Feminino , Humanos , Ativação Linfocitária/fisiologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Gravidade do Paciente , Risco
5.
Tohoku J Exp Med ; 253(1): 19-28, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33441511

RESUMO

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by arthritis of unknown etiology. JNK pathway-associated phosphatase (JKAP) is reported to be a negative regulator of T-cell activation, but its clinical role in JIA is unknown. This study aimed to investigate the correlation of JKAP with disease activity and treatment response to a tumor necrosis factor (TNF) inhibitor, etanercept (ETN), in JIA patients. Totally, 104 JIA patients (6.9 ± 2.7 years old) and 100 age- and sex-matched healthy controls (HCs) (7.2 ± 2.4 years old) were enrolled, and their serum samples were collected for measuring JKAP by enzyme-linked immunoassay. In JIA patients, after 24-week ETN treatment, clinical response was assessed based on the American College of Rheumatology pediatric criteria (ACRpedi) 50 criteria. Results showed that JKAP levels were significantly lower in JIA patients compared with HCs, and of good value in differentiating JIA patients from HCs. Among JIA patients, higher JKAP levels were associated with lower disease activity indexes, including C-reactive protein, number of joints with active arthritis, physician's global assessment of disease activity, and the present history of disease-modifying antirheumatic drugs; higher baseline JKAP levels were correlated with worse ACRpedi 50 response to ETN at week 24, and was also an independent predictive factor for worse ACRpedi 50 response to ETN. Thus, it may be inappropriate to use ETN for JIA patients with higher JKAP levels. In conclusion, serum JKAP is a potential biomarker for JIA activity and treatment response to a TNF inhibitor.


Assuntos
Artrite Juvenil/sangue , Artrite Juvenil/enzimologia , Fosfatases de Especificidade Dupla/sangue , Fosfatases da Proteína Quinase Ativada por Mitógeno/sangue , Artrite Juvenil/tratamento farmacológico , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Etanercepte/uso terapêutico , Feminino , Humanos , Masculino , Fatores de Risco , Resultado do Tratamento
6.
J Clin Lab Anal ; 33(7): e22945, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31206807

RESUMO

OBJECTIVE: This study aimed to explore the association of JKAP with sepsis risk and investigate its correlation with disease severity, inflammatory cytokines, and survival in sepsis patients. METHODS: A hundred and one sepsis patients along with 100 healthy controls were enrolled, and their blood serum samples were collected for JKAP and inflammatory cytokines measurement by enzyme-linked immunoassay. The difference in serum JKAP between sepsis patients and healthy controls was determined. Among sepsis patients, the correlation of JKAP with disease severity, laboratory indexes, inflammatory cytokines, 28-day mortality, and accumulating survival was analyzed. RESULTS: JNK pathway-associated phosphatase level was decreased in sepsis patients compared with healthy controls and presented with good value in predicting decreased sepsis risk (AUC = 0.896 [95% CI: 0.851-0.941]). And its low expression was associated with advanced disease severity (APACHE II score and SOFA score) and systemic inflammation (CRP, PCT, TNF-α, IL-1ß, IL-6, and IL-17) in sepsis patients. Additionally, JKAP level was decreased in deaths compared with survivors and had good value in distinguishing deaths from survivors (AUC = 0.742 [95% CI: 0.636-0.849]). Further, Kaplan-Meier curve analysis disclosed that JKAP high expression predicted more prolonged accumulating survival in sepsis patients. CONCLUSION: JNK pathway-associated phosphatase is of good value in predicting lower sepsis risk, and its downregulation correlates with advanced disease severity, higher level of systemic inflammation, and poor survival in sepsis patients.


Assuntos
Regulação para Baixo , Fosfatases de Especificidade Dupla/metabolismo , Inflamação/complicações , Inflamação/patologia , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Sepse/complicações , Sepse/patologia , Estudos de Casos e Controles , Citocinas/sangue , Fosfatases de Especificidade Dupla/sangue , Feminino , Humanos , Inflamação/sangue , Mediadores da Inflamação/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fosfatases da Proteína Quinase Ativada por Mitógeno/sangue , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Sepse/sangue , Sepse/mortalidade , Índice de Gravidade de Doença , Análise de Sobrevida
7.
Medicina (Kaunas) ; 55(5)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121943

RESUMO

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative disease that results in severe dementia. Having ischemic strokes (IS) is one of the risk factors of the AD, but the molecular mechanisms that underlie IS and AD are not well understood. We thus aimed to identify common molecular biomarkers and pathways in IS and AD that can help predict the progression of these diseases and provide clues to important pathological mechanisms. Materials and Methods: We have analyzed the microarray gene expression datasets of IS and AD. To obtain robust results, combinatorial statistical methods were used to analyze the datasets and 26 transcripts (22 unique genes) were identified that were abnormally expressed in both IS and AD. Results: Gene Ontology (GO) and KEGG pathway analyses indicated that these 26 common dysregulated genes identified several altered molecular pathways: Alcoholism, MAPK signaling, glycine metabolism, serine metabolism, and threonine metabolism. Further protein-protein interactions (PPI) analysis revealed pathway hub proteins PDE9A, GNAO1, DUSP16, NTRK2, PGAM2, MAG, and TXLNA. Transcriptional and post-transcriptional components were then identified, and significant transcription factors (SPIB, SMAD3, and SOX2) found. Conclusions: Protein-drug interaction analysis revealed PDE9A has interaction with drugs caffeine, γ-glutamyl glycine, and 3-isobutyl-1-methyl-7H-xanthine. Thus, we identified novel putative links between pathological processes in IS and AD at transcripts levels, and identified possible mechanistic and gene expression links between IS and AD.


Assuntos
Doença de Alzheimer/sangue , Biomarcadores/sangue , Isquemia Encefálica/sangue , 3',5'-AMP Cíclico Fosfodiesterases/análise , 3',5'-AMP Cíclico Fosfodiesterases/sangue , Doença de Alzheimer/complicações , Biomarcadores/análise , Isquemia Encefálica/complicações , Fosfatases de Especificidade Dupla/análise , Fosfatases de Especificidade Dupla/sangue , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/análise , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/sangue , Humanos , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/sangue , Fosfatases da Proteína Quinase Ativada por Mitógeno/análise , Fosfatases da Proteína Quinase Ativada por Mitógeno/sangue , Glicoproteína Associada a Mielina/análise , Glicoproteína Associada a Mielina/sangue , Receptor trkB/análise , Receptor trkB/sangue , Transdução de Sinais/fisiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Proteínas de Transporte Vesicular/análise , Proteínas de Transporte Vesicular/sangue
8.
J Parkinsons Dis ; 8(4): 529-537, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30248063

RESUMO

BACKGROUND: Parkinson's disease (PD) shares pathological and clinical features with progressive supranuclear palsy (PSP) patients making the diagnosis challenging. Distinguishing PD from PSP is crucial given differences in disease course, treatment and clinical management. OBJECTIVE: Although some progress has been made in the discovery of biomarkers for PD and PSP, there is an urgent need to identify additional biomarkers capable of distinguishing between these diseases. METHODS: In this study, we tested the phosphatases DUSP8 and PTPRC for their diagnostic potential using quantitative PCR assays, in blood of 138 samples from participants nested in the Parkinson's Disease Biomarkers Program. RESULTS: Relative abundance of PTPRC mRNA was downregulated in PSP patients compared to PD and healthy controls, whereas there was no significant difference in the expression of DUSP8. Interestingly, PTPRC mRNA correlated with the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score and MDS-UPDRS- part III, thus indicating it might be useful as part of a biosignature to stratify patients according to disease severity and progression. CONCLUSIONS: Collectively, these results suggest that PTPRC expression may be useful for distinguishing PD from PSP patients as part of a biosignature. Evaluation of PTPRC along with additional biomarkers in a larger and well-characterized longitudinal study is warranted.


Assuntos
Antígenos Comuns de Leucócito/sangue , Doença de Parkinson/diagnóstico , Paralisia Supranuclear Progressiva/diagnóstico , Idoso , Diagnóstico Diferencial , Regulação para Baixo , Fosfatases de Especificidade Dupla/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Doença de Parkinson/sangue , Paralisia Supranuclear Progressiva/sangue
9.
Arthritis Rheumatol ; 70(4): 528-536, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29287311

RESUMO

OBJECTIVE: Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS: Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS: Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION: Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity.


Assuntos
Artrite Reumatoide/genética , Citocromo P-450 CYP2E1/genética , Fosfatases de Especificidade Dupla/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Regiões Promotoras Genéticas/genética , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/patologia , Biomarcadores/sangue , Estudos de Coortes , Citocromo P-450 CYP2E1/sangue , Metilação de DNA , Fosfatases de Especificidade Dupla/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Fosfatases da Proteína Quinase Ativada por Mitógeno/sangue , Análise de Regressão , Índice de Gravidade de Doença
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