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1.
Zhongguo Zhong Yao Za Zhi ; 48(17): 4711-4721, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802810

RESUMO

This study aimed to investigate the protective effect and underlying mechanism of Mailuo Shutong Pills(MLST) on posterior limb swelling caused by femur fracture in rats. The rats were randomly divided into a sham operation group, a model group, a low-dose MLST group(1.8 g·kg~(-1)·d~(-1)), a high-dose MLST group(3.6 g·kg~(-1)·d~(-1)), and a positive drug group(60 mg·kg~(-1)·d~(-1) Maizhiling Tablets). The femur in the sham operation group was exposed and the wound was sutured, while the other four groups underwent mechanical damage to cause femur fracture. The rats were treated with corresponding drugs by gavage 7 days before modeling and 5 days after modeling, while those in the sham operation group and the model group were given an equivalent dose of distilled water by gavage. Hematoxylin-eosin(HE) staining was used to detect the pathological injury of the posterior limb muscle tissues in rats, and the degree of hind limb swelling was measured. The enzyme-linked immunosorbent assay(ELISA) kit was used to detect the expression levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α) in the serum of rats in each group. The activity of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and glutathione peroxidase(GSH-Px) in rat serum was also measured. Western blot was used to detect the protein expression levels of heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), and nuclear transcription factor E2-related factor 2(Nrf2) in rat posterior limb muscle tissues. The changes in the intestinal flora and intestinal metabolites in rats were detected by 16S rDNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), respectively, to explore the underlying mechanism of MLST in treating posterior limb swelling caused by femur fracture in rats. Compared with the model group, MLST significantly improved the degree of posterior limb swelling in rats, reduced the levels of serum inflammatory factors, and alleviated oxidative stress injury. The HE staining results showed that the inflammatory infiltration in the posterior limb muscle tissues of rats in the MLST groups was significantly improved. Western blot results showed that MLST significantly increased the protein expression of HO-1, NQO1, and Nrf2 in rat posterior limb muscle tissues compared with the model group. The 16S rDNA sequencing results showed that MLST improved the disorder of intestinal flora in rats after femur fracture. The UPLC-MS/MS results showed that MLST significantly affected the bile acid biosynthesis and metabolism pathway in the intestine after femur fracture, and the Spearman analysis confirmed that the metabolite deoxycholic acid involved in bile acid biosynthesis was positively correlated with the abundance of Turicibacter. The metabolite cholic acid was positively correlated with the abundance of Papilibacter, Staphylococcus, and Intestinimonas. The metabolite lithocholic acid was positively correlated with Papilibacter and Intestinimonas. The above results indicated that MLST could protect against the posterior limb swelling caused by femur fracture in rats. This protective effect may be achieved by improving the pathological injury of the posterior limb muscle, reducing the expression levels of inflammatory and oxidative stress-related factors in serum, reducing the oxidative injury of the posterior limb muscle, improving intestinal flora, and balancing the biosynthesis of bile acids in the intestine.


Assuntos
Microbioma Gastrointestinal , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Cromatografia Líquida , Tipagem de Sequências Multilocus , Espectrometria de Massas em Tandem , Estresse Oxidativo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Fêmur , Ácidos e Sais Biliares , DNA Ribossômico , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
2.
Mar Drugs ; 20(3)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35323500

RESUMO

Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and found that DSFF could activate macrophages. However, more investigations are needed to further evaluate whether DSFF could promote hematopoiesis in the chemotherapy process. In this study, the protective effect of DSFF (1.8-7.2 mg/kg, i.p.) on cyclophosphamide-induced hematopoietic damage in mice and the underlying mechanisms were investigated. Our results show that DSFF could restore the numbers of white blood cells, neutrophils, and platelets in the peripheral blood, and could also retard bone marrow cell decrease in mice with cyclophosphamide-induced hematopoietic damage. UPLC/Q-Extraction Orbitrap/MS/MS-based lipidomics results reveal 16 potential lipid biomarkers in a serum that responded to hematopoietic damage in mice. Among them, PC (20:1/14:0) and SM (18:0/22:0) were the key lipid molecules through which DSFF exerted protective actions. In a validation experiment, DSFF (6.25-100 µg/mL) could also promote K562 cell proliferation and differentiation in vitro. The current findings indicated that DSFF could affect the blood cells and bone marrow cells in vivo and thus showed good potential and application value in alleviating the hematopoietic damage caused by cyclophosphamide.


Assuntos
Ciclofosfamida/toxicidade , Hematopoese/efeitos dos fármacos , Agonistas Mieloablativos/toxicidade , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Sargassum , Animais , Biomarcadores/sangue , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , DNA/metabolismo , Humanos , Células K562 , Contagem de Leucócitos , Lipidômica , Camundongos , Neutrófilos/efeitos dos fármacos , Contagem de Plaquetas
3.
J Cell Mol Med ; 24(13): 7094-7101, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32406586

RESUMO

Interleukin (IL)-15 is a recently identified cytokine, which belongs to the interleukin-2(IL-2) family, and plays an important role in innate and adaptive immunoreaction. Given the fact that the structure of IL-15 is partially similar to IL-2, they share some common biological effects, including immunoregulation. IL-2 was proven to protect cardiac function in mouse myocardial infarction models. Cardiovascular diseases (CVDs) dominate the cause of mortality worldwide. Besides atherosclerosis, inflammation is also widely involved in the pathogenesis of many CVDs including hypertension, heart failure (HF) and aneurysm. IL-15, as a pro-inflammatory cytokine, is up-regulated in some cardiovascular diseases, such as myocardial infarction and atherosclerosis. The current understanding of IL-15, including its signal pathway and cellular function, was described. Furthermore, IL-15 has a protective effect in myocardial infarction and myocarditis by decreasing cardiomyocyte death and improving heart function. The inhibited effect of IL-15 in ductus arteriosus (DA) should be focused on. IL-15 promoted atherogenesis. IL-15 may be a good target in treatment of cardiovascular diabetology. Finally, future research direction of IL-15 deserves attention. Since IL-15 plays several roles in CVDs, understanding the role of the IL-15/IL-15R system may provide a scientific basis for the development of new approaches that use IL-15 for the treatment of CVDs.


Assuntos
Doenças Cardiovasculares/metabolismo , Interleucina-15/metabolismo , Animais , Biomarcadores/metabolismo , Glucose/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Interleucina-15/química , Modelos Cardiovasculares
4.
Arthritis Rheum ; 64(10): 3240-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22674011

RESUMO

OBJECTIVE: MicroRNA (miRNA) plays a role in autoimmune diseases. MiRNA-223 (miR-223) is up-regulated in patients with rheumatoid arthritis (RA) and is involved in osteoclastogenesis, which contributes to erosive disease. The aim of this study was to test the feasibility of using lentiviral vectors expressing the miR-223 target sequence (miR-223T) to suppress miR-223 activity as a therapeutic strategy in a mouse model of collagen-induced arthritis (CIA). METHODS: Levels of miR-223 in the synovial tissue of patients with RA or osteoarthritis (OA), as well as in the ankle joints of mice with CIA, were determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Lentiviral vectors expressing miR-223T (LVmiR-223T) or luciferase short hairpin RNA (LVshLuc) as a control vector were injected intraperitoneally into mice with CIA. Treatment responses and disease-related bone mineral density were monitored. Levels of nuclear factor 1A (NF-1A), a direct target of miR-223, and macrophage colony-stimulating factor receptor (M-CSFR), which is critical for osteoclastogenesis, were measured by immunohistochemistry and quantitative RT-PCR. Osteoclasts were assessed by tartrate-resistant acid phosphatase staining. RESULTS: MiR-223 expression was significantly higher in the synovium of RA patients and in the ankle joints of mice with CIA as compared to OA patients and normal mice. LVmiR-223T treatment reduced the arthritis score, histologic score, miR-223 expression, osteoclastogenesis, and bone erosion in mice with CIA. Down-regulation of miR-223 with concomitant increases in NF-1A levels and decreases in M-CSFR levels was detected in the synovium of LVmiR-223T-treated mice. CONCLUSION: This study is the first to demonstrate that lentivirus-mediated silencing of miR-223 can reduce disease severity of experimental arthritis. Furthermore, our results indicate that inhibition of miR-223 activity should be further explored as a therapeutic strategy in RA.


Assuntos
Artrite Experimental/genética , MicroRNAs/genética , Membrana Sinovial/metabolismo , Animais , Articulação do Tornozelo/metabolismo , Articulação do Tornozelo/patologia , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Densidade Óssea/genética , Modelos Animais de Doenças , Inativação Gênica , Humanos , Lentivirus , Camundongos , MicroRNAs/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Membrana Sinovial/patologia
5.
J Clin Rheumatol ; 19(5): 252-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23872548

RESUMO

BACKGROUND: Opportunistic infection has been documented in systemic lupus erythematosus with special attention paid to Pneumocystis jirovecii because of the significant morbidity and high mortality. OBJECTIVES: The limited large-scale investigations covering P. jirovecii pneumonia (PCP) in systemic lupus erythematosus following biologics or immunosuppressants therapy prompted us to perform this study in southern Taiwan. METHODS: A retrospective study was completed in 858 hospitalized lupus patients from January 2000 to December 2011. The definite diagnosis of PCP was made by the laboratory detection of Pneumocystis organisms together with consistent clinical and radiological manifestations of PCP. Positive polymerase chain reaction results of sputum samples were not regarded as infection in this study, unless P. jirovecii was the sole pathogen found and pulmonary manifestations resolved following antibiotics for PCP treatment alone. RESULTS: The laboratory identification of Pneumocystis organisms depended on lung biopsy in 2 cases and bronchoalveolar lavage in 3 patients. Five cases, 2 women and 3 men aged 30 to 50 years (41.8 ± 8.8 years), were identified with a 0.6% incidence. None received chemoprophylactics against P. jirovecii infection. All had lupus nephritis and lymphopenia with low CD4 T-cell counts. Prior usages of higher daily prednisolone dosages and concomitant biologics or immunosuppressants were observed in all patients. Pneumocystis jirovecii pneumonia contributed to a high mortality rate (60%). CONCLUSIONS: We report the rare occurrence but high mortality of PCP infection in this study. A consensus guideline addressing prophylactic antibiotics against Pneumocystis organisms in highest-risk lupus patients on biologics or immunosuppressants could be helpful in guiding their management.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Infecções Oportunistas/microbiologia , Infecções Oportunistas/mortalidade , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/mortalidade , Adulto , Biópsia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/terapia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Fatores de Risco , Escarro/microbiologia , Taiwan/epidemiologia
6.
Ann Rheum Dis ; 71(4): 524-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22072014

RESUMO

OBJECTIVES: Patients with primary Sjögren's syndrome (pSS) are at a higher risk of developing non-Hodgkin's lymphoma (NHL). However, little is known with regard to the risk of developing cancers other than NHL. The authors aimed in this study to compare the incidence of cancer in various sites among patients with pSS with the general population of Taiwan. METHODS: The authors used National Health Insurance claims data to establish a nationwide population cohort of 7852 patients with pSS from 2000 to 2008 who did not have cancer prior to diagnosis of pSS. Incidence and standardised incidence ratios (SIRs) for cancer in various sites were calculated. RESULTS: Among patients with pSS, 277 (2.9%) developed cancer. The SIR for cancer was 1.04 (95% CI 0.91 to 1.18) among patients of all ages with pSS and was 2.19 (95% CI 1.43 to 3.21) for patients aged 25-44 years. Female patients with pSS had a higher risk of NHL (SIR 7.1, 95% CI 4.3 to 10.3), multiple myeloma (SIR 6.1, 95% CI 2.0 to 14.2) and thyroid gland cancer (SIR 2.6, 95% CI 1.4 to 4.3) and a lower risk of colon cancer (SIR 0.22, 95% CI 0.05 to 0.65). In contrast, male patients with pSS were not at a higher risk of developing cancer in particular sites. CONCLUSION: Patients with pSS, overall, did not have higher risk of cancer, and only patients aged 25-44 years were at an increased risk of cancer compared with their counterparts in the general population. Cancer screening for patients with pSS, especially female patients, should focus on NHL and multiple myeloma and thyroid gland cancer.


Assuntos
Neoplasias/etiologia , Síndrome de Sjogren/complicações , Adulto , Distribuição por Idade , Idoso , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Distribuição por Sexo , Síndrome de Sjogren/epidemiologia , Taiwan/epidemiologia
7.
Front Psychol ; 12: 647351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017285

RESUMO

Amid the social background of China where the Internet has penetrated into every corner of an adolescent's life, we were concerned of the role of Internet usage in influencing the educational gap among social classes. We investigated the mediating role of Internet usage preference for entertainment in the relationship between the family socioeconomic status (SES) and the adolescent's academic achievement and explored the moderating role of future orientation in the relationship. A total of 614 junior high school students were recruited to complete a questionnaire survey, including questionnaires for family SES, Internet usage preference, and adolescent future orientation. The results showed that (1) the relationship between family SES and academic achievement was mediated by Internet usage preference for entertainment; (2) the indirect effect was moderated by future orientation, such that the negative association between family SES and Internet usage preference for entertainment was only indicated in adolescents with low future orientation; and (3) the direct association between family SES and Internet usage preference for entertainment was moderated by future orientation.

8.
Front Psychol ; 12: 714346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539515

RESUMO

This study explored the mediating effects of resilience and future orientation on the relationship between family socioeconomic status (SES) and learning engagement within the context of Chinese culture based on the cognitive theory of social class. A total of 1,245 junior high school students were recruited to complete anonymous questionnaires regarding the objective and subjective SES of their families, resilience, future orientation, and learning engagement. The mediating effects were tested by stepped multiple linear regression. Results indicated the following: (1) the relationships between objective and subjective SES, resilience, future orientation, and learning engagement was significantly positive; (2) resilience only mediated the relationship between subjective SES and learning engagement, whereas future orientation mediated the relationships between objective/subjective SES and learning engagement; (3) resilience and future orientation sequentially mediated the relationship between subjective SES and learning engagement. The current study contributes to a better understanding of how family SES influences adolescent academic performance from the perspective of adolescent cognitive abilities. In addition, this study provides implications for the prevention and intervention of academic performance of poor adolescents due to low SES.

9.
J Formos Med Assoc ; 109(1): 85-8, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20123591

RESUMO

Hemophagocytic syndrome (HS) that occurs in the course of adult-onset Stills disease (AOSD) has been reported only rarely in the literature. HS and AOSD share overlapping clinical and laboratory features, therefore, it is difficult to recognize HS as a complication of AOSD. Here, we report the case of a 46-year old woman with classical features of AOSD. Severe pancytopenia and jaundice associated with extreme hyperferritinemia occurred during high-dose steroid treatment. Bone marrow biopsy showed typical pathological features of hemophagocytosis, which confirmed the coexistence of HS with AOSD. The patient was treated with methylprednisolone pulse therapy of 500 mg/day for 3 days, as recommended in cases of HS complicating AOSD, and her condition improved gradually. During the disease course, extensive studies could not identify any viral infection or other known underlying etiology for the reactive hemophagocytosis. Currently, the patient is in remission on low-dose prednisolone and azathioprine.


Assuntos
Linfo-Histiocitose Hemofagocítica/complicações , Doença de Still de Início Tardio/complicações , Azatioprina/uso terapêutico , Medula Óssea/patologia , Quimioterapia Combinada , Feminino , Febre/etiologia , Glucocorticoides/administração & dosagem , Humanos , Imunossupressores/uso terapêutico , Linfo-Histiocitose Hemofagocítica/patologia , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Pulsoterapia , Doença de Still de Início Tardio/tratamento farmacológico , Doença de Still de Início Tardio/patologia , Resultado do Tratamento
10.
J Formos Med Assoc ; 109(9): 680-3, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20863997

RESUMO

Tuberculous myositis, which mimics rheumatic symptoms, is an extremely rare disease. Clinical ambiguity easily leads to misdiagnosis and delayed initial treatment. We present the case of a 55-year-old man who had primary Sjögren's syndrome and active cutaneous vasculitis treated with steroid and immunosuppressive drugs. He presented with a swollen, painful, hot left thigh. Although anti-tuberculosis medications were administered soon after a positive acid-fast stain of incisional muscular tissue, he died of rapidly progressive tuberculous myositis and multiorgan failure following 18 days of hospitalization. This case is presented to increase the awareness of this rare entity in clinical practice.


Assuntos
Músculo Esquelético/patologia , Miosite/etiologia , Síndrome de Sjogren/complicações , Tuberculose/etiologia , Biópsia , Evolução Fatal , Humanos , Hospedeiro Imunocomprometido , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/microbiologia , Miosite/patologia , Síndrome de Sjogren/diagnóstico , Tuberculose/patologia
11.
ACR Open Rheumatol ; 2(7): 401-406, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32530139

RESUMO

OBJECTIVE: Current evidence highlights a link between insulin resistance (IR) and disease activity in rheumatoid arthritis (RA), suggesting that insulin sensitivity can be improved by treating patients with TNF-α blockers. Although reduced IR has been shown in RA patients who receive monoclonal antibody treatment, the efficacy remains to be elucidated when using recombinant soluble receptor fusion proteins. In particular, etanercept (ETA) is capable of blocking lymphotoxin-α, a cytokine-related to IR-associated disease status. METHODS: A prospective study was carried out in nondiabetic active RA patients receiving a 25-mg subcutaneous ETA injection twice weekly. RESULTS: Thirty patients aged 31 to 73 years (50.9 ± 10.6), naïve to biological and targeted synthetic disease-modifying antirheumatic drugs with DAS28 scores of 5.17 to 7.49 (6.11 ± 0.66), were classified into high-IR and low-IR groups based on their baseline homeostatic model assessment (HOMA)-IR levels. No differences were found between the two groups in terms of age, sex, weight, body mass index, seropositivity, and medication profiles before the injection. After a 24-week therapeutic period, there were reduced HOMA-IR levels in all patients in the high-IR group (3.390 ± 0.636 to 2.234 ± 0.870, P < 0.001). A greater decrease in DAS28 values was found in patients with reduced IR than those without a reduction (2.54 ± 0.67 versus 1.46 ± 0.46, P = 0.006) in the low-IR group. CONCLUSION: We observed an improvement in insulin sensitivity in nondiabetic active RA patients following 24-week recombinant soluble TNF-α receptor fusion protein therapy.

12.
J Biomed Biotechnol ; 2009: 406136, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19759858

RESUMO

Programmed death-1 (PD-1) was shown to deliver an inhibitory signal after binding to its ligands, PD-L1 (B7-H1) or PD-L2 (B7-DC). Recently, up-regulated expression of PD-1 molecule and/or its ligands was demonstrated in human diseases including rheumatoid arthritis and inflammatory colitis. The study aimed to investigate the expression and function of PD-1 and PD-1 ligands on circulating T cells, B cells and monocytes from patient with systemic lupus erythematosus (SLE). The results showed that patients with SLE had significantly increased percentages of PD-1-expressing CD3+T cells and CD19+B cells, PD-L1-expressing CD19+B cells and PD-L2-expressing CD14+B monocytes. In selected SLE patients and normal subjects, functional study of PD-1/ PD-1 ligands pathway on the production of cytokines by stimulated PBMC was examined. Blockages of PD-1 or PD-1 ligands substantially increased the production of IL-2, IFN-gamma and IL-10, the amplitude of increase roughly ranged from one to three times. There were no significant differences of the enhancing effects on cytokine production by blockage of PD-1/PDL pathway between SLE patients and normal subjects. The study indicates that there are no intrinsically defective expression and function of PD-1 and PD-1 ligands on PBMC in patients with SLE.


Assuntos
Antígenos CD/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Antígenos CD/biossíntese , Antígenos CD/imunologia , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/imunologia , Antígeno B7-H1 , Complexo CD3/imunologia , Complexo CD3/metabolismo , Citocinas/biossíntese , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Leucócitos Mononucleares/imunologia , Receptores de Lipopolissacarídeos/imunologia , Receptores de Lipopolissacarídeos/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Proteína 2 Ligante de Morte Celular Programada 1 , Receptor de Morte Celular Programada 1 , Transdução de Sinais , Estatísticas não Paramétricas
13.
Clin Rheumatol ; 38(5): 1361-1366, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30767092

RESUMO

Elevated IL-17 levels with higher Th17 numbers are identified in systemic lupus erythematosus (SLE). STAT3 signaling plays a crucial role in the Th17 generation, and SOCS3 negatively regulates their formation. We investigated IL-17, STAT3, and SOCS3 expression, and analyzed their correlations to elucidate the regulatory mechanisms of IL-17 production in SLE. This study enrolled 32 patients, and venous mononuclear cells (MNCs) were isolated with further purification of CD4-positive T cells. IL-17 and SOCS3 levels were measured by real-time quantitative PCR, and pSTAT3/STAT3 expression was analyzed by immunoblot. Elevated IL-17 and SOCS3 levels were identified in lupus patients. There were higher IL-17 levels in lupus nephritis (class IV) than in SLE without renal involvement. Positive correlations were found between IL-17 levels and SOCS3 expression, lupus activity (SLEDAI-2K), or daily proteinuria. There were higher intensities of pSTAT3/ß-actin and STAT3/ß-actin in SLE, and a positive correlation between IL-17 expression and pSTAT3/ß-actin or STAT3/ß-actin intensity. Lupus nephritis (class IV) had higher STAT3/ß-actin intensity than SLE without renal involvement. These results suggest upregulated STAT3/IL-17 expression in lupus patients. Such findings might facilitate the development of novel compounds and the application of existing therapeutics targeting the STAT3/IL-17 signal in SLE.


Assuntos
Interleucina-17/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Adulto , Linfócitos T CD4-Positivos/imunologia , Feminino , Citometria de Fluxo , Humanos , Interleucina-17/genética , Leucócitos Mononucleares/metabolismo , Modelos Lineares , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Masculino , Fator de Transcrição STAT3/genética , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas/genética , Taiwan , Células Th17/imunologia , Regulação para Cima
14.
Sci Rep ; 7(1): 13165, 2017 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-29030592

RESUMO

Despite a high prevalence of ankylosing spondylitis (AS) in Han Chinese, the clinical experience remains very limited in the extra-articular presentation of inflammatory bowel disease (IBD). A monocentric retrospective study was performed for the AS-associated IBD manifestation. This study analyzed AS patients fulfilling the 1984 revised New York diagnostic criteria, excluding those who had the onset of IBD before or concurrently with the diagnosis of AS, for their demographic, clinical, laboratory, radiological, pathological and medication data, particularly in the usage of anti-TNF monoclonal antibody. Among 988 AS patients with 19.8% female, 4 (0.4%) had the overt IBD presentation, one female and 3 male aged 28 to 47 years (38.8 ± 4.6), all ulcerative colitis with the characteristic histopathological findings. At the onset of colitis, all had a long-term disease duration of 10 to 25 years (17.5 ± 6.5) and high BASDAI 7.5 to 8.8 (8.2 ± 0.5) with the hip joint involvement. There were recurrent flares of colitis despite the treatment with corticosteroids and messalazopyrin/salazopyrin, and no relapses of IBD were observed for 6.0 ± 1.1 years after the adalimumab (ADA) therapy. In this retrospective cohort, we demonstrate the rarity of AS-associated IBD manifestation in Han Chinese with a beneficent effect from the ADA therapy.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Espondilite Anquilosante/epidemiologia , Adalimumab/uso terapêutico , Adolescente , Adulto , Anti-Inflamatórios/uso terapêutico , Criança , Feminino , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
15.
Disabil Rehabil ; 39(4): 338-345, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26883482

RESUMO

Purpose This study investigates the effects of kinematic disturbances in rheumatoid thumb on patient's hand functions via objective and patient-perceived measurements. Method Twenty-one patients with rheumatoid arthritis (RA) and 21 healthy age- and gender-matched individuals were recruited to receive the objective evaluations, including the Purdue Pegboard Test, Jamar dynamometer, pinch-meter, Permanent Impairment Scale and self-administrated measurements, including the Health Assessment Questionnaire (HAQ) and Manual Ability Measure-36 (MAM-36). An electromagnetic tracking system was used to measure thumb kinematics. The differences in the measures between the RA and control groups and the dominant and non-dominant hands of the RA group were examined. The relationships between the thumb kinematics and hand functional capabilities, as well as impairment levels, were also explored. Results The RA group showed significantly smaller thumb movement capabilities and hand strength, as well as worse scores in hand dexterity, MAM-36 and HAQ than healthy controls. The movement workspace of the RA thumb showed moderate correlations with the factors of hand strength, dexterity, impairment scale, MAM-36 and HAQ scores. Conclusions The findings indicate deficits related to the movement capability of the RA thumb may negatively influence hand dexterity and functional hand performance, as well as life quality, for the patients with RA. Implications for Rehabilitation A deformed rheumatoid thumb might limit the movement workspace of the thumb and consequently impair the hand performance as well as the life quality. The dominant thumb of the RA patients might have greater structural and functional deterioration than the non-dominant side. Suitable joint protection strategies, exercises and orthotics should be early applied to the RA patients for preserving hand functions.


Assuntos
Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/reabilitação , Polegar/fisiopatologia , Atividades Cotidianas , Fenômenos Biomecânicos , Estudos de Casos e Controles , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Taiwan , Resultado do Tratamento
16.
Semin Arthritis Rheum ; 46(1): 102-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26992634

RESUMO

OBJECTIVES: Although the data from primary antiphospholipid syndrome (APS) suggests a beneficial effect of rituximab usage, its therapeutic role remains to be defined in systemic lupus erythematosus (SLE)-associated APS, a complex clinical situation with thrombotic events and lupus activity. METHODS: A single-center retrospective analysis of rituximab usages in APS was performed in 800 hospitalized SLE patients. RESULTS: There were 63 SLE-associated APS cases with 6 on rituximab therapy, all female aged 37.7 ± 9.0 years with 1 catastrophic and 16 thrombotic episodes. Therapeutic indications included warfarin failure despite the adequate target international normalized ratio with an average duration of 17.3 ± 11.2 months between the thrombotic recurrences. After the rituximab therapy, there was no relapse of thrombosis with a mean follow-up period of 39.3 ± 20.9 months, and a decrease in lupus activity (SLEDAI-2K, 9.7 ± 5.5 to 5.3 ± 2.2). Infection complications were observed, including episodes of bronchitis and urinary tract infection. CONCLUSIONS: In this single-center study with largest case numbers and a long-term follow-up period, there were no recurrent thrombotic events after the rituximab therapy, implicating further consideration of large-scale trials enrolling more ethnic groups to evaluate its therapeutic role in SLE-associated APS patients.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Rituximab/uso terapêutico , Adulto , Síndrome Antifosfolipídica/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
17.
Clin Rheumatol ; 35(3): 747-50, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26245723

RESUMO

T cell activation participates in the pathogenesis of rheumatoid arthritis (RA), and the signaling molecule zeta-chain-associated protein kinase 70 kDa (ZAP-70) plays a crucial role in this process. Different mutations in the coding sequence of ZAP-70 are involved in a variety of immunological phenotypes, and recent evidence indicates that genetic variations within the 3' untranslated regions (UTR) of microRNA binding sites may affect the hybridization with target mRNAs, leading to phenotype changes with disease status. In this study, we evaluated the possible effect of ZAP-70 polymorphism as a genetic risk factor in RA by examining the single-nucleotide polymorphism in 100 patients and 100 ethnicity- and sex-matched healthy individuals from southern Taiwan. In both groups, the genotype distribution of rs2278699 in the 3' UTR was in the Hardy-Weinberg equilibrium. In RA, there were higher frequencies of the G allele (15.5 versus 8.0 %, odds ratio 2.1, P = 0.020) and significant differences in the trend of various genotypes (P = 0.024). The results suggest that genetic polymorphism in the 3' UTR of ZAP-70 is associated with RA susceptibility in southern Taiwanese.


Assuntos
Artrite Reumatoide/genética , Povo Asiático/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Regiões 3' não Traduzidas , Alelos , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Humanos , Fenótipo , Taiwan , Proteína-Tirosina Quinase ZAP-70
18.
J Microbiol Immunol Infect ; 38(5): 358-60, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16211145

RESUMO

Several autoimmune diseases have been reported to be associated with common variable immunodeficiency disease (CVID), including rheumatoid arthritis and Sjögren's syndrome. On the other hand, approximately 20-30% of patients with rheumatoid arthritis develop secondary Sjögren's syndrome. A 26-year-old woman had a 6-year history of chronic symmetric polyarthritis and 3-year history of sicca syndrome prior to admission for pneumonia. Rheumatoid arthritis with secondary Sjögren's syndrome had been diagnosed 1 year before. The patient had experienced 3 episodes of pneumonia during the previous 3 years. Markedly depressed serum immunoglobulin levels prompted a suspicion of common variable immunodeficiency, and the impression was confirmed after a series of examinations. Monthly administration of intravenous immunoglobulin (IVIG) alleviated the polyarthritis and improved the sicca syndrome. IVIG replacement therapy was ultimately successful in curing recurrent bacterial infections, chronic polyarthritis, and improving the severity of sicca syndrome.


Assuntos
Artrite Reumatoide/complicações , Imunodeficiência de Variável Comum/diagnóstico , Síndrome de Sjogren/complicações , Adulto , Artrite Reumatoide/diagnóstico , Imunodeficiência de Variável Comum/terapia , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulinas/sangue , Imunoglobulinas Intravenosas/administração & dosagem , Pneumonia/diagnóstico , Síndrome de Sjogren/diagnóstico
19.
Eur J Dermatol ; 15(5): 396-400, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16172052

RESUMO

Cutaneous mucinosis secondary to autoimmune collagen vascular disease is well recognized, but manifestation as cellulitis-like massive cutaneous mucinosis preceding dermatomyositis is unusual. Here we report a 21-year-old Taiwanese woman with a large, rapid onset, painful erythematous, edematous plaque, which histopathologically revealed septal panniculitis with fat necrosis and massive mucin deposition. Incapacitated muscle weakness of proximal extremities, generalized edema, heliotrope erythema, and Gottron's papules developed in a short period of time with high titers of serum muscle enzyme. Serological titers of ANA, anti-dsDNA, anti-ENA panels, and erythrocyte sedimentation rate, however, all showed unremarkable results. Diagnosis of dermatomyositis was confirmed by electromyographic findings of myopathy. As the disease progressed, large, deep cutaneous ulceration and vesiculobullous lesions also developed. In spite of aggressive treatment, the patient died 9 months after the disease onset, probably due to the complication of gastrointestinal ischemia and perforation.


Assuntos
Dermatomiosite/complicações , Enteropatias/complicações , Mucinoses/complicações , Pioderma Gangrenoso/complicações , Dermatopatias Vesiculobolhosas/complicações , Vasculite/complicações , Adulto , Dermatomiosite/patologia , Evolução Fatal , Feminino , Humanos , Mucinoses/patologia , Debilidade Muscular/complicações , Pioderma Gangrenoso/patologia , Dermatopatias Vesiculobolhosas/patologia , Úlcera Cutânea/complicações , Úlcera Cutânea/patologia
20.
Arthritis Rheumatol ; 67(1): 39-50, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25303734

RESUMO

OBJECTIVE: The transcription factor Snail is involved in various biologic functions. We hypothesized that this molecule regulates tumor necrosis factor α (TNFα)-mediated synovial fibroblast activation in the rheumatoid joint. The aim of this study was to examine the role of Snail in the expression of cadherin-11 (Cad-11) and myofibroblast markers, interleukin-6 (IL-6) production, and the invasive ability of cells. METHODS: Synovium samples were obtained from patients with rheumatoid arthritis (RA) and from rats with collagen-induced arthritis (CIA). Synovial fibroblasts were treated with TNFα or a Wnt signaling inducer, and the joints of rats with CIA were injected with a TNFα antagonist. Modulation of Snail expression in the synovial fibroblasts and joints was performed by lentiviral vector-mediated transfer of complementary DNA or short hairpin RNA. RESULTS: The expression of Snail and Cad-11 was higher in synovium and synovial fibroblasts from patients with RA compared with patients with osteoarthritis and was increased in rats with CIA. TNFα stimulation or activation of Wnt signaling up-regulated the expression of Snail, Cad-11, and α-smooth muscle actin (α-SMA) in synovial fibroblasts, and anti-TNFα therapy down-regulated the expression of Snail, Cad-11, and α-SMA in the joints of rats with CIA. Although synovial fibroblast transfectants in which Snail was overexpressed showed increased expression of Cad-11 and α-SMA and enhanced TNFα-mediated invasive capacity and IL-6 production, synovial fibroblast transfectants from rats with CIA in which Snail was silenced showed decreased expression and had the opposite effect on these functions. Normal joints in which Snail was overexpressed had hyperplastic synovium, with increased expression of Cad-11, α-SMA, and IL-6. Silencing Snail expression ameliorated arthritis, with reduced Cad-11 expression and reduced levels of extracellular matrix deposition in the joints of rats with CIA, whereas overexpression of Snail exacerbated arthritis, with increased Cad-11 expression and increased levels of extracellular matrix deposition. CONCLUSION: Our results demonstrate that Snail regulates TNFα-mediated activation of synovial fibroblasts in the rheumatoid joint. These findings may contribute to the pharmacologic development of therapeutics targeting synovial fibroblasts in patients with RA.


Assuntos
Artrite Experimental/fisiopatologia , Artrite Reumatoide/fisiopatologia , Fibroblastos/fisiologia , Articulações/fisiopatologia , Membrana Sinovial/fisiopatologia , Fatores de Transcrição/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Actinas/metabolismo , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Biomarcadores/metabolismo , Caderinas/metabolismo , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Humanos , Interleucina-6/metabolismo , Articulações/metabolismo , Articulações/patologia , Masculino , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoartrite/fisiopatologia , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição da Família Snail , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Fator de Necrose Tumoral alfa/farmacologia , Via de Sinalização Wnt/fisiologia
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