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1.
Dermatol Ther ; 35(4): e15303, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34984792

RESUMO

Chronic spontaneous urticaria (CSU) is characterized by the spontaneous development of wheals, itching, and/or angioedema, for ≥6 weeks. In China, non-sedating H1-antihistamines (H1AH) are the recommended first-line treatment, with escalation up to 4× the standard dose in symptomatic patients to achieve control. Treatment options for Chinese patients who remain symptomatic on H1AH treatment are limited. This 20-week randomized, double blind, placebo-controlled, parallel-group study investigated the efficacy and safety of omalizumab as an add-on therapy for the treatment of patients with CSU who remained symptomatic despite H1AH treatment in China. Adult patients (N = 418) diagnosed with refractory CSU for ≥6 months were randomized (2:2:1) to receive omalizumab 300 mg (OMA300), omalizumab 150 mg (OMA150) or placebo, subcutaneously, every 4 weeks. Primary outcome was change from baseline to week 12 in weekly itch severity score (ISS7). Safety was assessed by rates of adverse events (AEs). Demographic and disease characteristics at baseline were comparable across treatment groups. At week 12, statistically significant greater decreases from baseline were observed in ISS7 with OMA300 (least square mean difference [LSM]: -4.23; 95% confidence interval [CI]: -5.70, -2.77; p < 0.001) and OMA150 (LSM: -3.79; 95% CI: -5.24, -2.33; p < 0.001) versus placebo. Incidence of treatment-emergent AEs over 20 weeks was slightly higher with OMA300 (71.3%) compared to OMA150 and placebo groups (64.7% and 63.9%, respectively). The incidences of serious AEs were balanced between groups. This study demonstrated the efficacy and safety of omalizumab in Chinese adult patients with CSU who remained symptomatic despite H1AH therapy.


Assuntos
Antialérgicos , Urticária Crônica , Urticária , Adulto , Antialérgicos/efeitos adversos , Doença Crônica , Urticária Crônica/diagnóstico , Urticária Crônica/tratamento farmacológico , Antagonistas dos Receptores Histamínicos H1 , Humanos , Omalizumab/efeitos adversos , Resultado do Tratamento , Urticária/induzido quimicamente , Urticária/diagnóstico , Urticária/tratamento farmacológico
2.
Allergy Asthma Immunol Res ; 14(1): 131-142, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34983113

RESUMO

Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients (r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels (P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.

3.
An. bras. dermatol ; 96(4): 416-421, July-Aug. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1285085

RESUMO

Abstract Background: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. Objective: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. Methods: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. Results: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. Conclusion: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.


Assuntos
Humanos , Psoríase , Interferon gama , Leucócitos Mononucleares , Citocinas , Interleucinas , Interferons
4.
An Bras Dermatol ; 96(4): 416-421, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34030913

RESUMO

BACKGROUND: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. OBJECTIVE: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. METHODS: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. RESULTS: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. CONCLUSION: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.


Assuntos
Interferon gama , Psoríase , Citocinas , Humanos , Interferons , Interleucinas , Leucócitos Mononucleares
5.
Allergy Asthma Clin Immunol ; 17(1): 38, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865428

RESUMO

BACKGROUND: IL-35 is a newly anti-inflammatory cytokine that belongs to the IL-12 family. Mast cells, as one of the major effector cells in the immune response system, plays an important role in the pathogenesis of chronic spontaneous urticarial (CSU). Our study aims to explore the inhibited role of IL-35 in HMC-1. METHODS: The effects of IL-35 on cell proliferation, cytokine expression, and histamine release in a human mast cell line (HMC-1) were investigated by CCK8, ELISA, or RT-PCR. The phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells was detected by Western Blot. RESULTS: We found that IL-35 significantly inhibited the proliferation of HMC-1 cells stimulated by PMA and A23187. IL-35 also down-regulates the release of histamine and the mRNA expression of IL-6 and IL-17 in activated HMC-1. Furthermore, IL-35 markedly inhibited the phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells. CONCLUSIONS: This study provides the first observations on the inhibitory and anti-inflammatory effect of IL-35 in activated HMC-1 cells. We suggest that IL35 may play an inhibited role in the pathogenesis of CSU.

6.
Chin Med J (Engl) ; 133(22): 2665-2673, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33060370

RESUMO

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.


Assuntos
Anticorpos Monoclonais , Psoríase , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , China , Método Duplo-Cego , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
7.
Dermatol Ther ; 33(6): e14263, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32869931

RESUMO

Psoriasis is a chronic, recurrent skin disease requiring long-term management. Agents that repair the skin's barrier function are invaluable additives in topical treatments of psoriasis. This multicenter, randomized, controlled trial evaluated the efficacy and safety of a linoleic acid-ceramide-containing moisturizer (LA-Cer) for mild-to-moderate psoriasis vulgaris. We randomized 178 patients from both northern and southern regions of China into two groups: 81 patients in the control group received mometasone furoate (MF, 0.1%) cream, while MF in combination with LA-Cer was administered to 86 patients in the treatment group for 4 weeks. The LA-Cer-MF group maintained the use of moisturizer after topical glucocorticoid administration. The primary endpoint, Psoriasis Area and Severity Index 50 (PASI 50) response, revealed the superiority of LA-Cer-MF with lower relapse rates at week 8. The use of the LA-Cer-containing moisturizer as maintenance therapy resulted in a continuous improvement in the clinical state in terms of body surface area, PASI, investigators' assessment of skin dryness and desquamation, and Physician Global Assessment of Psoriasis score, and in the patients' quality of life. Thus, the LA-Cer-containing moisturizer is a promising agent to prevent and treat psoriasis as it enhances the therapeutic effect induced by topical glucocorticoids and delays relapse.


Assuntos
Psoríase , Adulto , Ceramidas , China , Método Duplo-Cego , Feminino , Humanos , Ácido Linoleico , Masculino , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento
8.
Arch Dermatol Res ; 312(6): 437-445, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31873772

RESUMO

Etanercept biosimilar recombinant human tumour necrosis factor-α receptor II: IgG Fc fusion protein (rhTNFR-Fc, trade name Yisaipu) has shown good efficacy in the treatment of moderate-to-severe plaque psoriasis. To compare the efficacy and safety of rhTNFR-Fc plus methotrexate (MTX) and rhTNFR-Fc plus placebo in Chinese patients with moderate-to-severe plaque psoriasis. In this multicentre, randomized, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned in a 1:1 ratio to receive rhTNFR-Fc plus MTX or rhTNFR-Fc plus placebo. The primary endpoint was the proportion of patients achieving Psoriasis Area and Severity Index improvement of at least 75% (PASI 75) from baseline at week 24. Adverse events (AEs) were recorded to evaluate safety. Efficacy analysis was performed using the intent-to-treat principle. A total of 466 patients were enrolled and randomly received rhTNFR-Fc plus MTX (combination group, n = 233) or rhTNFR-Fc plus placebo (monotherapy group, n = 233). PASI 75 at week 24 was significantly higher in the combination group than in the monotherapy group (81.86% vs. 65.50%, p < 0.001). Similar results were observed in other PASI improvement scores at week 12 [PASI 75, 62.39% vs. 44.54% (p < 0.001); PASI 50, 87.17% vs. 75.55% (p = 0.001); and PASI 90, 34.07% vs. 18.78% (p < 0.001)] and week 24 [PASI 50, 92.48% vs. 85.59% (p = 0.019); and PASI 90, 64.16% vs. 42.36% (p < 0.001)]. Significantly more patients had a static Physicians' Global Assessment of clear or almost clear in the combination group than in the monotherapy group at week 12 (26.46% vs. 12.50%, p < 0.001) and week 24 (62.38% vs. 40.83%, p < 0.001). The most common AEs in the two groups were upper respiratory tract infection and abnormal liver function. The combination therapy of rhTNFR-Fc plus MTX was an effective therapy for moderate-to-severe plaque psoriasis with an acceptable safety and tolerability profile, indicating that it was feasible and well tolerated for patients.


Assuntos
Etanercepte/uso terapêutico , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/genética , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Receptores Tipo II do Fator de Necrose Tumoral/genética , Proteínas Recombinantes de Fusão/genética , Adulto , Medicamentos Biossimilares , China , Método Duplo-Cego , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Mediators Inflamm ; 2019: 4952131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814803

RESUMO

Background: Thrombin could elicit degranulation of mast cells involved in numerous physiologic and pathologic processes; however, the detailed scrutiny of this procedure and further research of possible cell signaling pathways are lacking. Methods: P815 mouse mast cells were exposed to various concentrations of thrombin for 16 h. Expression of protease-activated receptor (PAR)1, PAR2, PAR3, and PAR4 mRNA in P815 was analyzed by quantitative real-time PCR (qRT-PCR) and the fittest concentration of thrombin was decided. Then, secretions of mediators from P815 stimulated by thrombin 0.2 U/ml were determined using enzyme-linked immunosorbent assay (ELISA) and Luminex liquichip; the possible cell signaling pathways were measured by immunoblotting. Furthermore, inhibition of thrombin inhibitor (hirudin), PAR1 inhibitor (SCH79797), and MAPK inhibitors (SB203580, PD98059, and SP600125) on the mediator section was evaluated by ELISA and Luminex liquichip. Results: Thrombin 0.2 U/ml induced the elevated expression of PAR1, PAR2, PAR3, and PAR4, as well as the increasing level of phospho-IκBα, phospho-SAPK/JNK MAPK, phospho-P38 MAPK (Thr180/Tyr182), and phospho-ERK1/2 MAPK (p44/42) in P815. Secretion of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin- (IL-) 2, IL-6, chemokine ligand- (CCL-) 2, chemokine (C-X-C motif) ligand- (CXCL-) 1, and CXCL-5 from P815 increased apparently; this effect could be diminished by hirudin, whereas SCH79797 and MAPK inhibitors (SB203580, PD98059, and SP600125) diminish the secretions with weaker effect. Conclusion: We found the expression of PAR mRNA in P815, activation of signaling pathways of nuclear factor-kappaB (NF-κB), and mitogen-activated protein kinases (MAPKs) including C-Jun NH2-terminal kinase (JNK), P38, and extracellular signal-regulated kinase 1/2 (ERK1/2), and the release of multiple inflammatory mediators stimulated by thrombin, as well as the inhibition of the inflammatory releases by hirudin, SCH79797, and MAPK inhibitors including SB203580, PD98059, and SP600125.


Assuntos
Citocinas/metabolismo , Receptor PAR-1/metabolismo , Receptor PAR-2/metabolismo , Receptores de Trombina/metabolismo , Trombina/farmacologia , Animais , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(5): 720-724, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30378333

RESUMO

OBJECTIVE: To investigate serum levels and mRNA expressions of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor CD163 from the patients with psoriasis vulgaris (PV). METHODS: Peripheral blood samples were obtained from 28 patients with PV and 15 healthy control subjects. Serum levels of TWEAK and CD163 were detected by ELISA, mRNA expressions of TWEAK and CD163 in peripheral blood were analyzed by real time-PCR, and protein expressions of TWEAK and CD163 were determined by flow cytometry. RESULTS: All the 28 PV patients were in progressive stage at the beginning of this study, 10 patients then recovered in convalescent stage after treatment. Compared to healthy controls, PV patients had higher serum TWEAK levels and lower serum CD163 levels. Serum TWEAK level in progressive stage was significantly higher than that in convalescent stage. Serum CD163 level were elevated significantly in convalescent stage compared with those in progressive stage. TWEAK mRNA expression in PV patients were significantly lower than that in healthy controls, but there was no significant differences of CD163 mRNA expression. TWEAK expression in monocytes in progressive stage and convalescent stage were significantly higher than that of controls, CD163 expression in monocytes in progressive stage and convalescent stage significantly lower than that in controls. No correlations wene found between psoriasis area and severity index (PASI) score and expression of TWEAK and CD163. CONCLUSION: TWEAK/CD163 pathway may play a role in PV.


Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Citocina TWEAK/sangue , Psoríase/sangue , Receptores de Superfície Celular/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Monócitos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
14.
Oncotarget ; 8(35): 59446-59454, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28938649

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a common skin disorder with elevated prevalence. Cataract induced by AD rarely occurs in adolescent and young adult patients, which is also called atopic cataract. Using whole exome sequencing, we aimed to explore genetic alterations among AD and atopic cataract. RESULT: We recruited a 19 year-old Chinese male with AD accompanied with cataracts, his father with AD and his mother without AD or cataract. Through analysis of the exomic sequence of the 3 individuals from the same family, we identified that with respect to AD, there were 162 genes mutated in both this patient and his father but not in his mother. In addition, we found 10 genes mutated in this patient only without in his parents according to cataract. CONCLUSION: This research suggests that coinheritance of mutations in these genes may correlate with AD, and the pathogenesis of AD complicated with cataracts was related to genetic factors.

15.
Ann Allergy Asthma Immunol ; 118(6): 704-709, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28583263

RESUMO

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease characterized by recurrent itchy wheals with or without angioedema that lasts longer than 6 weeks. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that plays critical roles in angiogenesis and endothelial permeability. OBJECTIVE: To investigate serum levels of soluble VE (sVE)-cadherin in patients with CSU. METHODS: Serum levels of sVE-cadherin in patients with CSU, patients with atopic dermatitis, and healthy controls were determined by enzyme-linked immunosorbent assay. In addition, changes in sVE-cadherin serum levels were compared in patients with CSU before and after H1 antihistamine treatment. Furthermore, the effects of histamine on sVE-cadherin release by HMEC-1 cells were determined by enzyme-linked immunosorbent assay. The inhibition effects of H1 antihistamine and H2 antihistamine on sVE-cadherin release, VE-cadherin phosphorylation, and VE-cadherin disruption were evaluated in histamine-treated HMEC-1 cells by western blot and immunofluorescence. RESULTS: Serum levels of sVE-cadherin in patients with CSU were significantly higher than those in patients with atopic dermatitis and healthy controls. Serum sVE-cadherin levels in patients with CSU were correlated with the severity of CSU according to Urticaria Activity Scores. Furthermore, serum sVE-cadherin levels in patients with CSU at pretreatment decreased after H1 antihistamine treatment. In addition, histamine markedly induced sVE-cadherin release in HMEC-1 cells. Moreover, H1 antihistamine, but not H2 antihistamine, significantly inhibited sVE-cadherin release in histamine-treated HMEC-1 cells. Western blot data showed that histamine induced phosphorylation of VE-cadherin in HMEC-1 cells, which was blocked by H1 antihistamine. CONCLUSION: The present data showed serum levels of sVE-cadherin are increased in patients with CSU. Histamine-induced sVE-cadherin release from endothelial cells could play a role in the pathogenesis of CSU.


Assuntos
Antígenos CD/sangue , Caderinas/sangue , Urticária/sangue , Adolescente , Adulto , Antígenos CD/imunologia , Caderinas/imunologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Criança , Doença Crônica , Dermatite Atópica/sangue , Dermatite Atópica/imunologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Feminino , Histamina/farmacologia , Humanos , Masculino , Fosforilação/efeitos dos fármacos , Índice de Gravidade de Doença , Adulto Jovem
16.
J Dermatol ; 44(5): 573-581, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27943400

RESUMO

In the previous work, we have indicated that HMGB1, a pro-inflammatory cytokine, is closely associated with the pathogenesis of psoriasis. To further clarify the role of HMGB1 in the pathogenesis of psoriasis, we investigated the direct function of HMGB1 application and HMGB1 blockade in imiquimod (IMQ)-induced psoriatic mouse model in this study. Mice were treated with imiquimod (IMQ) to induce psoriasis-like inflammation, and consecutively injected with recombinant HMGB1 or phosphate-buffered saline (PBS) i.d. Abundant cytoplasmic expression of HMGB1 was observed in lesional skin from IMQ-treated skin. The injection of HMGB1 into the IMQ-treated skin further aggravated the psoriasis-like disease, enhanced the infiltration of CD3+ T cells, myeloperoxidase+ neutrophils and CD11c+ dendritic cells, increased the number of γδ T cells, and upregulated the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-17 compared with the PBS injection. Finally, by using anti-HMGB1 monoclonal antibody or HMGB1 inhibitor glycyrrhizin, we indicated that HMGB1 blockade reduced the number of γδ T cells, suppressed the mRNA expression of IL-6, TNF-α, IFN-γ and IL-17, and moderated clinical and histological evolvement in the IMQ-treated skin. Our data suggest that HMGB1 may act as a pro-inflammatory cytokine, and contribute to the development of IMQ-induced psoriasis-like inflammation. HMGB1 blockade may represent a new direction in the suppression of psoriasis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Proteína HMGB1/metabolismo , Psoríase/imunologia , Aminoquinolinas , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Ácido Glicirrízico/farmacologia , Imiquimode , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/metabolismo
17.
Lipids Health Dis ; 15: 103, 2016 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-27245937

RESUMO

BACKGROUND: Several studies have been performed to investigate the relationship between psoriasis and epicardial fat tissue (EFT). However, the number of patients of every single study is relatively small. OBJECTIVES: We carried out a meta-analysis to evaluate whether EFT is associated with psoriasis. METHODS: A search of PubMed, Ovid Embase, Ovid Medline, the Cochrane Library and Chinese BioMedical Literature Database (CBM) for controlled trials was done from inception to January 20th, 2016. Published trials that included a psoriasis group and a control group without psoriasis with data for at least epicardial fat tissue (EFT) were included. All statistical analyses were conducted using the Stata 12.0 (Stata Corporation, College Station, TX, USA). RESULTS: There were 5 trials involving 731 patients. Patients with psoriasis showed significantly higher EFT than control group (SMD: 0.86, 95 % CI: 0.27-1.46, P = 0.004). CONCLUSIONS: Patients with psoriasis have higher EFT compared to control subjects without psoriasis.


Assuntos
Tecido Adiposo/patologia , Doenças Cardiovasculares/patologia , Pericárdio/patologia , Psoríase/patologia , Tecido Adiposo/diagnóstico por imagem , Adulto , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/etiologia , Ensaios Clínicos como Assunto , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/diagnóstico por imagem , Psoríase/complicações , Psoríase/diagnóstico por imagem , Fatores de Risco , Tomografia Computadorizada por Raios X
18.
Chin Med J (Engl) ; 129(7): 757-62, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-26996468

RESUMO

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD. METHODS: A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. RESULTS: A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. CONCLUSION: Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.


Assuntos
Dermatite Atópica/diagnóstico , Adolescente , Adulto , Dermatite Atópica/imunologia , Eczema/diagnóstico , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
19.
Can J Physiol Pharmacol ; 92(10): 859-65, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25272089

RESUMO

Monoammonim glycyrrhizate (MAG) derived from licorice has been shown to have anti-inflammatory properties. Chemokines are vital inflammatory mediators that are involved with endothelial damage from leukocyte infiltrates in various inflammatory skin diseases. In this study, we investigated the anti-inflammatory effects and mechanisms of MAG on tumor necrosis factor-α (TNF-α) induced chemokine production in a human dermal microvascular endothelial cell line (HMEC-1). HMEC-1 cells were treated with TNF-α, with or without MAG. The results showed that MAG suppressed TNF-α-induced chemokine (including CXCL8, CX3CL1, and CXCL16) mRNA expression in HMEC-1 cells, in a dose-dependent manner, and reduced the secretion of these chemokines in culture supernatant. Moreover, endothelial activation in the presence of MAG blocked the chemotactic activities of TNF-α-stimulated HMEC-1 cell supernatant on the migration of primary neutrophils and primary monocytes. In addition, Western blot and immunofluorescence data revealed that MAG inhibited nuclear translocation of nuclear factor-κB p65 (NF-κB p65). It is the first report to demonstrate that MAG suppresses TNF-α-induced chemokine production in HMEC-1 cells, and that the mechanism may be inhibiting the translocation of NF-κB p65 into the nucleus to prevent the starting of inflammatory signaling pathway. Our results revealed that MAG is a potential anti-inflammatory agent capable of improving inflammatory skin diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Núcleo Celular/metabolismo , Quimiocinas/biossíntese , Ácido Glicirrízico/farmacologia , Fator de Transcrição RelA/metabolismo , Transporte Ativo do Núcleo Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quimiotaxia de Leucócito/efeitos dos fármacos , Endotélio Vascular/citologia , Humanos , Microvasos/citologia , Pele/irrigação sanguínea , Fator de Necrose Tumoral alfa/farmacologia
20.
Ann Dermatol ; 26(3): 303-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24966628

RESUMO

BACKGROUND: Henoch-Schönlein purpura (HSP) is an immune complex-mediated disease predominantly characterized by the deposition of circulating immune complexes containing immunoglobulin A (IgA) on the walls of small vessels. Although the pathogenesis of HSP is not yet fully understood, some researchers proposed that B-cell activation might play a critical role in the development of this disease. OBJECTIVE: To investigate the serum levels of visfatin (pre-B-cell colony-enhancing factor), B-cell-activating factor (BAFF), and CXCL13, and to analyze their association with disease severity. METHODS: The serum levels of visfatin, BAFF, and CXCL13 were measured by using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 43 patients with HSP and 45 controls. The serum levels of IgA anticardiolipin antibodies (ACA) were detected by using a double-antigen sandwich ELISA. RESULTS: Levels of visfatin but not BAFF and CXCL13 were significantly elevated in the sera of patients with HSP in the acute stage, and restored to normal levels in the convalescent stage. Furthermore, serum levels of visfatin were significantly higher in patients with HSP having renal involvement than in those without renal involvement. Serum levels of visfatin were correlated with the severity of HSP and serum concentration of ACA-IgA. CONCLUSION: We show for the first time that the serum levels of visfatin are abnormally elevated in patients with HSP. Visfatin may be associated with the pathogenesis of HSP.

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