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2.
Trials ; 21(1): 999, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33276811

RESUMO

OBJECTIVES: A severe epidemic of COVID-19 has broken out in China and has become a major global public health event. We focus on the Acute Respiratory Distress Syndrome (ARDS)-like changes and overactivation of Th17 cells (these produce cytokines) in patients with COVID-19. We aim to explore the safety and efficacy of ixekizumab (an injectable drug for the treatment of autoimmune diseases) to prevent organ injury caused by the immune response to COVID-19. Ixekizumab is a human monoclonal antibody that binds to interleukin-17A and inhibits the release of pro-inflammatory cytokines and chemokines. TRIAL DESIGN: The experiment is divided into two stages. In the first stage, the open trial, 3 patients with COVID-19 are treated with ixekizumab, and the safety and efficacy are observed for 7 days. In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. This is a two-center, open-label, randomized controlled pilot trial with 2-arm parallel group design (1:1 ratio). PARTICIPANTS: Patients with COVID-19 aged 18-75 with increased Interleukin (IL)-6 levels will be enrolled, but patients with severe infections requiring intensive care will be excluded. The trial will be undertaken in two centers. The first stage is carried out in Xiangya Hospital of Central South University, and the second stage is carried out simultaneously in the Third Xiangya Hospital of Central South University. INTERVENTION AND COMPARATOR: In the first stage, three subjects are given ixekizumab ("Taltz") (80 mg/ml, 160 mg as a single hypodermic injection) and antiviral therapy (α-interferon (administer 5 million U by aerosol inhalation twice daily), lopinavir/ritonavir (administer 100mg by mouth twice daily, for the course of therapy no more than 10 days), chloroquine (administer 500mg by mouth twice daily, for the course of therapy no more than 10 days), ribavirin (administer 500mg by intravenous injection two to three times a day, for the course of therapy no more than 10 days), or arbidol (administer 200mg by mouth three times a day, for the course of therapy no more than 10 days), but not more than 3 types). The treatment course of the first stage is 7 days. In the second stage, 40 randomized patients will receive the following treatments--Group 1: ixekizumab (80 mg/ml, 160 mg as a single hypodermic injection) with antiviral therapy (the same scheme as in the first stage); Group 2: antiviral therapy alone (the same scheme as in the first stage). The length of the second treatment course is 14 days. MAIN OUTCOMES: The primary outcome is a change in pulmonary CT severity score (an imaging tool for assessing COVID-19, which scores on the basis of all abnormal areas involved). Pulmonary CT severity score is assessed on the 7th day, 14th day, or at discharge. RANDOMISATION: In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. The eLite random system of Nanjing Medical University is used for randomization. BLINDING (MASKING): The main efficacy indicator, the CT results, will be evaluated by the third-party blinded and independent research team. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. TRIAL STATUS: Trial registration number is ChiCTR2000030703 (version 1.7 as of March 19, 2020). The recruitment is ongoing, and the date recruitment was initiated in June 2020. The anticipated date of the end of data collection is June 2021. TRIAL REGISTRATION: The name of the trial register is the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2000030703 ( http://www.chictr.org.cn/ ). The date of trial registration is 10 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

4.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(7): 804-811, 2020 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879084

RESUMO

OBJECTIVES: Psoriasis is a chronic inflammatory skin disease that affects adults and children. The most common subtype is psoriasis vulgaris. This article analyzes the characteristics and clinical features of children with psoriasis vulgaris to strengthen the understanding, treatment, and management for children with psoriasis. METHODS: A total of 208 children with psoriasis vulgaris, who were first admitted to the Department of Dermatology, Xiangya Hospital, Central South University from October 2012 to December 2018, were retrospectively analyzed. Their clinical characteristics, results of laboratory examination, treatment options and efficacy were summarized. RESULTS: The age of the 208 children with psoriasis vulgaris was (11.19±3.97) years old, the peak incidence was 12 years old, the disease duration was (27.46±31.30) months, and the male-female ratio was 1∶0.96. The most common site of the first attack was the scalp (37.98%), followed by the trunk (26.44%) and the limbs (22.12%). The causes leading to exacerbation were more common in infections and diets. There were 33 patients (15.87%) with a family history of psoriasis, showing the higher score of Psoriasis Area and Severity Index (PASI) and the higher Dermatological Quality of Life Index (DLQI) (both P<0.05). In all patients, 29 cases (13.94%) were overweight, 19 cases (9.14%) were obese, and the rate of overweight and obesity in children with psoriasis vulgaris was higher than that of normal children in China. In the laboratory test, the serum levels of 25-hydroxyvitamin D (25-OH-VD) were decreased in most patients (47.5%), and the serum 25-OH-VD levels were found to be moderately negatively correlated with PASI score (P<0.05). The score of DLQI in the patient was 5.56±3.57, the score of PASI was 7.25±6.83, and they were positively correlated (r=0.409, P<0.001). In most patients (72.11%), the severity of the disease was mild to moderate. Their treatment was often dominated by topical drugs and Chinese patent medicine (65.67%). Retinoids showed a good effect on children. Cyclosporine and methotrexate were effective in more severe cases. CONCLUSIONS: Children with psoriasis vulgaris are mainly caused by infection and diet. Patients with family history have more serious illness, lower quality of life, and are more likely to have metabolic abnormalities such as overweight and obesity. The serum 25-OH-VD levels in children with psoriasis vulgaris are negatively correlated with the score of PASI.


Assuntos
Obesidade Pediátrica , Psoríase/epidemiologia , Adolescente , Adulto , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença
5.
J Cell Mol Med ; 24(20): 11646-11655, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32916775

RESUMO

The skin is the main barrier between the human body and the outside world, which not only plays the role of a physical barrier but also functions as the first line of defence of immunology. Langerhans cells (LCs), as dendritic cells (DC) that play an important role in the immune system, are mainly distributed in the epidermis. This review focuses on the role of these epidermal LCs in regulating skin threats (such as microorganisms, ultraviolet radiation and allergens), especially psoriasis. Since human and mouse skin DC subsets share common ontogenetic characteristics, we can further explore the role of LCs in psoriatic inflammation.

6.
Patient Prefer Adherence ; 14: 1403-1409, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884243

RESUMO

Purpose: The COVID-19 epidemic has caused difficulties in continuous treatment for patients with chronic diseases and resulted in nonadherence to treatment and adverse health outcomes. This study aimed to investigate the associations of nonadherence to treatment with patient-reported outcomes of psoriasis during the COVID-2019 epidemic. Methods: A cross-sectional study among Chinese patients with psoriasis was conducted through a web-based questionnaire survey during 25 Feb 2020 and 6 Mar 2020. Demographic and clinical data, nonadherence to treatment, and patient-reported outcomes were collected. The outcomes included deterioration of the disease condition, perceived stress, and symptoms of anxiety and depression. Logistic regression was used to investigate the associations. Results: A total of 926 questionnaires were collected. A total of 634 (68.5%) reported nonadherence to treatment, and worse adherence was found among patients receiving systemic treatment (adjusted odds ratio [AOR]: 2.67; 95% CI: 1.40-5.10) and topical treatment (AOR: 4.51; 95% CI: 2.66-7.65) compared to biological treatment. Nonadherence to treatment (less than two weeks and more than two weeks) was significantly associated with deterioration of psoriasis (aOR: 2.83 to 5.25), perceived stress (AOR: 1.86 to 1.57), and symptoms of anxiety (AOR: 1.42 to 1.57) and depression (AORs: 1.78). Subgroup analysis by treatment showed consistent results in general. Conclusion: Nonadherence to treatment was associated with the aggravation of psoriasis conditions, perceived stress, and symptoms of anxiety and depression.

8.
Front Med (Lausanne) ; 7: 236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626717

RESUMO

Background: Psoriasis is a chronic recurrent inflammatory disease involving many common mechanisms associated with obesity, such as systemic inflammation and vitamin D deficiency. This study aimed to examine the association of the serum concentration of 25-hydroxyvitamin D with psoriasis and the effect modification by obesity among the affected patients. Methods: A mixed cross-section study was conducted. We consecutively included untreated psoriasis patients from the outpatients who visited the Department of Dermatology of Xiangya Hospital and recruited 205 gender-matched healthy controls from the Hunan Civil Servant Cohort. In both groups, we measured the serum 25-hydroxyvitamin D level, body mass index (BMI), waist-hip-ratio (WHR) and other psoriasis-related clinical indicators. Results: A total of 203 psoriasis outpatients and 205 gender-matched cohort participants with complete data of serum vitamin D concentration were included in the analysis. The serum vitamin D levels of the two groups were close to each other, while the mean WHR of the psoriasis outpatients was significantly higher. Compared with the controls, the risk of psoriasis increased significantly when the vitamin D level decreased from 20 to 10 nmol/L. A significant interaction between the serum vitamin D level and the obesity category (BMI × WHR) was identified. After stratification by WHR, vitamin D was not associated with psoriasis in subjects with normal WHR. In contrast, the association between vitamin D deficiency and psoriasis retained and the effect size augmented in patients with central obesity. Conclusions: WHR may modify the association between serum vitamin D and psoriasis. Treatment advocating Vitamin D supplements may tailor to psoriasis patients with metabolic disorders.

9.
J Dermatol Sci ; 99(3): 146-151, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32600738

RESUMO

Skin diseases bring great psychological and physical impacts on patients, however, a considerable number of skin diseases still lack effective treatments, such as psoriasis, systemic lupus erythematosus, melanoma and so on. Receptor-interacting serine threonine kinase 1 (RIPK1) plays an important role in cell death, especially necroptosis, associated with inflammation and tumor. As many molecules modulate the ubiquitination of RIPK1, disruption of this checkpoint can lead to skin diseases, which can be ameliorated by RIPK1 inhibitors. This review will focus on the molecular mechanism of RIPK1 activation in inflammation as well as the current knowledges on the contribution of RIPK1 in skin diseases.

10.
Mediators Inflamm ; 2020: 8567320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32684837

RESUMO

Psoriasis is a common immune-mediated, chronic inflammatory genetic-related disease that affects patients' quality of life. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of progenitor and immature myeloid cells which are expanded in psoriatic skin lesions and peripheral blood. However, the role of MDSCs in the pathogenesis of psoriasis remains unclear. Here, we confirmed that the accumulation of human MDSCs is remarkably increased in skin lesions of psoriasis patients by flow cytometry. Depleting MDSCs by Gemcitabine significantly suppresses IMQ-induced psoriatic inflammation and epidermal thickening as well as Th17 and Treg cell accumulation. Moreover, through the RNA-Seq technique, we validated some differentially expressed genes on CD4+ T-cells of IMQ-induced-MDSC-depleted mice such as IL-21 and Timd2, which are involved in Th17-cell differentiation or T-cell activation. Interestingly, neutralizing IL-21R by antibody reduces IMQ-induced epidermal thickening through downregulating the infiltration of MDSCs and Th17 cells. Our data suggest that targeting myeloid-derived suppressor cells is a novel strategy for antipsoriasis therapy. IL-21 may be a potential therapeutic target in psoriasis.

11.
J Am Acad Dermatol ; 83(2): 670-672, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32407741
12.
J Med Econ ; 23(7): 737-743, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32223358

RESUMO

Aims: This study aims to develop a mapping algorithm that can be used to predict 5-level EQ-5D (EQ-5D-5L) utility scores from the Psoriasis Disability Index (PDI) for further use in cost-utility analysis among psoriasis patients.Materials and Methods: A total of 321 participants with psoriasis was recruited in a dermatology clinic from a tertiary hospital in China. The EQ-5D-5L utility scores were scored using the Chinese-specific value set. Three model specifications were used and each one was estimated using three different statistical techniques, including the ordinary least squares (OLS), the Tobit regression and the generalized linear model (GLM). The goodness-of-fit of mapping performance was estimated by using two common indicators: the mean absolute error (MAE) and the mean square error (MSE).Results: A final validated sample of 321 psoriasis patients was analyzed in the study. The patients had a mean ± standard deviation (SD) age of 39.7 ± 12.9 years, and the EQ-5D-5L state utility score is 0.899 ± 0.106. Among all the models considered, the OLS linear model based on the four PDI item scores was selected as the best model due to higher accuracy (MAE = 0.1334 and 0.1557 for the estimation and validation sample separately).Limitations: The main limitation of this study is that the survey site was limited to one hospital and not more broadly representing the whole of China. Additionally, there are some missing data in the full sample and an absence of an external dataset to validate the algorithms.Conclusions: The mapping algorithms reported in this paper can be used to predict the EQ-5D-5L utilities from the PDI; however, similar to other mapping studies in the literature it can only serve as the second-best approach to elicit utilities from disease-specific instruments.

13.
Eur J Dermatol ; 30(6): 674-679, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33459259

RESUMO

BACKGROUND: The product of Physician Global Assessment (PGA) and Body Surface Area (BSA) (PGA × BSA) has been proposed as a simple and sensitive instrument for measuring psoriasis severity. OBJECTIVES: To assess the simple measure, PGA × BSA, with respect to criterion validity, reproducibility, responsiveness, and interpretability among Chinese patients with psoriasis. MATERIALS & METHODS: Assessments of psoriasis severity were performed by two dermatologists independently for the baseline survey and by one dermatologist during follow-up. Criterion validity and reproducibility were assessed using Spearman correlation coefficients (r). Responsiveness was assessed by comparing the percentage changes in PGA × BSA (PGA × ΔBSA [%]) between patients grouped by disease improvement. The receiver operating characteristic (ROC) curve was used to determine the threshold of PGA × ΔBSA for disease improvement, anchored by 50% and 75% reduction in Psoriasis Area Severity Index (PASI). RESULTS: A total of 276 patients participated in the baseline survey, of whom 93 were followed. PGA × BSA highly correlated with PASI (r = 0.94), Simplified PASI (SPASI, r = 0.93), and Psoriasis Log-based Area and Severity Index (PLASI, r = 0.90) measured at baseline, indicating good criterion validity. The between-evaluator consistency of PGA × BSA was r = 0.95, indicating high reproducibility. PGA × ΔBSA highly correlated with both ΔPASI (r = 0.86) and ΔPLASI (r = 0.85), suggesting good responsiveness. The threshold of ΔPGA × BSA for disease improvement was 57% and 73%, as indicated by 50% and 75% reduction in PASI, respectively. CONCLUSION: PGA × BSA demonstrates good biometric properties and may be used to measure the severity of psoriasis among Chinese patients.

15.
Psychol Res Behav Manag ; 12: 97-106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30799963

RESUMO

Background: Previous observational studies have shown comorbidity between psoriasis and psychological disorders. However, the evidence of the efficacy of psychological interventions, including cognitive behavioral therapy (CBT) and other treatments, on psoriasis is still debated. Objectives: The aim of this study was to systematically review the psychological interventions used in the treatment of psoriasis and to meta-analyze the efficacy of psychological interventions on psoriasis with respect to area and severity reduction. Materials and methods: A systematic review and meta-analysis were conducted. PubMed, Web of Science, EMbase, and major Chinese academic journal databases were searched for articles published before January 2018. Studies of randomized controlled trials (RCTs) that applied psychological interventions in the treatment of psoriasis and used area and severity as the outcome measures were meta-analyzed. The pooled mean difference between groups was estimated using either fixed-effects models or random-effects models in the presence of heterogeneity. Subgroup analysis was performed by method of intervention and severity of psoriasis. Results: Out of the 4,152 potentially relevant studies, 8 RCTs were included. The pooled mean difference was -1.36 (95% CI: -2.52 to -0.19; P=0.02). The pooled estimate was -1.80 (95% CI: -2.57 to -1.03; P<0.001) for CBT intervention and was -0.70 (95% CI: -2.39 to 0.99; P=0.42) for non-CBT intervention. The pooled estimates for mild and moderate-to-severe psoriasis were -1.95 (95% CI: -3.91 to 0.00; P=0.05) and -0.61 (95% CI: -1.61 to 0.38; P=0.23), respectively. Conclusion: CBT is effective in the treatment of psoriasis in terms of area and severity reduction. Systemic treatment does not further enhance the efficacy of CBT. The effect of the psychological intervention is stronger in patients with moderate-to-severe psoriasis.

16.
Acta Derm Venereol ; 99(3): 321-326, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30521061

RESUMO

The association of atopic dermatitis and chronic spontaneous urticaria with socioeconomic status has been little studied. The aim of this study was to investigate the prevalence of skin diseases and their association with socioeconomic status in adolescents in China. A cross-sectional study was conducted at Central South University, Changsha, China. All newly enrolled students underwent dermatological examination and completed a survey. Socioeconomic status was measured in terms of parental education level and income. Two-level logistic regression models were used. A total of 8,226 students consented to participate. On dermatological examination, moderate to severe acne (10.2%) had the highest prevalence, followed by chronic spontaneous urticaria (2.7%), atopic dermatitis (2.5%), and tinea (1.7%). Socioeconomic status was positively associated with the prevalence of chronic spontaneous urticaria (ptrend = 0.001) and atopic dermatitis (ptrend = 0.0094). Tinea was inversely associated with socioeconomic status (ptrend = 0.025). Higher parental socioeconomic status was associated with higher risk of atopic dermatitis and chronic spontaneous urticaria, but lower risk of tinea.


Assuntos
Dermatite Atópica/epidemiologia , Pais , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Urticária/epidemiologia , Adolescente , Distribuição por Idade , China/epidemiologia , Doença Crônica , Estudos Transversais , Dermatite Atópica/diagnóstico , Dermatite Atópica/economia , Escolaridade , Feminino , Inquéritos Epidemiológicos , Humanos , Renda , Masculino , Pais/educação , Prevalência , Medição de Risco , Fatores de Risco , Determinantes Sociais da Saúde/economia , Urticária/diagnóstico , Urticária/economia , Adulto Jovem
17.
J Pediatr ; 204: 256-262.e3, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30274928

RESUMO

OBJECTIVES: To investigate the association of soft drink consumption and the intake of sugar from soft drinks with the prevalence of acne in adolescents. STUDY DESIGN: This was a university-based epidemiologic investigation that included 8226 students who underwent health examinations and a questionnaire survey inquiring about the intake of soft drinks. Skin diseases were diagnosed by certificated dermatologists during the health examination. Two-level logistic and generalized additive models were used to estimate the associations, and aORs were presented as the effect size. RESULTS: A total of 8197 student survey responses were analyzed. Frequent intake (≥7 times per week) of carbonated sodas (aOR 1.61, 95% CI 0.96-2.72), sweetened tea drinks (aOR 2.52, 95% CI 1.43-4.43), and fruit-flavored drinks (aOR 1.90, 95% CI 1.18-3.07) was associated with moderate-to-severe acne after adjustments for confounders. The occasional intake of fruit-flavored drinks (1-2 times per week) had a weak protective effect on acne (aOR 0.86, 95% CI 0.74-0.99). The intake of sugar from any soft drinks showed a nonlinear association with acne (P < .01), and sugar intake ≥100 g/d was significantly associated with moderate-to-severe acne (aOR 3.12, 95% CI 1.80-5.41). CONCLUSIONS: Daily soft drink consumption significantly increases the risk of moderate-to-severe acne in adolescents, especially when the sugar intake from any type of soft drink exceeds 100 g per day.


Assuntos
Acne Vulgar/epidemiologia , Bebidas Gaseificadas/efeitos adversos , Açúcares da Dieta/efeitos adversos , Acne Vulgar/etiologia , Adolescente , Grupo com Ancestrais do Continente Asiático , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
18.
Int J Oncol ; 53(6): 2397-2408, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272281

RESUMO

Cluster of differentiation (CD)147, as a transmembrane glycoprotein, is highly expressed in a variety of tumors. Accumulating evidence has demonstrated that CD147 serves critical roles in tumor cell death and survival; however, the underlying mechanism requires further investigation. In the present study, it was revealed that CD147 knockdown significantly increased melanoma cell apoptosis. In addition, downregulation of CD147 reversed the malignant phenotype of melanoma, as demonstrated by the induction of tumor cell apoptosis in a xenograft mouse model. In addition, a human apoptosis antibody array was performed and 9 differentially expressed apoptosis-related proteins associated with CD147 were identified, including insulin-like growth factor-binding protein 2 (IGFBP2). Additionally, CD147 knockdown was observed to significantly decreased IGFBP2 expression at the mRNA and protein levels in melanoma cells. Providing that IGFBP2 is a downstream molecule in the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, the effects of CD147 on this particular pathway were investigated. Interestingly, the expression of phosphorylated (p)-AKT and p­mechanistic target of rapamycin was attenuated, whereas PTEN was markedly upregulated in CD147-underexpressing melanoma cells. Furthermore, application of a PI3K­specific inhibitor also decreased IGFBP2 expression. Importantly, IGFBP2 was highly expressed in clinical tissues of melanoma compared with the control group, and its expression exhibited a positive association with CD147. The present study revealed that CD147 served a critical role in mediating the apoptosis of melanoma cells via IGFBP2 and the PTEN/PI3K/AKT signaling pathway. IGFBP2 and CD147 were observed to be overexpressed in clinical melanoma tissues; IGFBP2 was shown to be positively associated with CD147 expression, suggesting that CD147 may be considered as a potential therapeutic target for chemotherapy or prevention for in melanoma.


Assuntos
Basigina/genética , Regulação para Baixo , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Melanoma/patologia , Animais , Apoptose , Basigina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/genética , Melanoma/metabolismo , Camundongos , Transplante de Neoplasias , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(8): 835-842, 2018 Aug 28.
Artigo em Chinês | MEDLINE | ID: mdl-30197310

RESUMO

OBJECTIVE: To explore the role of methotrexate (MTX) in regulating the number of regulatory T cells (Treg) and the mRNA expression of transcription factor Foxp3.
 Methods: 1) We analyzed the number of Treg and the mRNA expression of Foxp3 by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR) respectively in patients with psoriasis vulgaris, patients with psoriasis vulgaris after the 8-week treatment of MTX, and healthy people. 2) BALB/c female mice were smeared with imiquimod (IMQ) cream for 6 days. We recorded the change of the lesion in mice every day. The morphological changes of lesion in mice were evaluated by the psoriasis area and severity index (PASI) and HE staining. 3) The mouse model was randomly divided into a control group and an MTX group. The MTX group was treated with different doses of MTX (38.5 and 77.0 nmol/L) on the third day of this experiment. The morphological changes of lesion in mice were evaluated by PASI and HE staining. We tested the number of Treg and the expression level of Foxp3 mRNA in splenic lymphocytes.
 Results: 1) The number of Treg and the expression level of Foxp3 mRNA were lower in psoriasis vulgaris patients than those in the healthy control group (P<0.05). After 8-week treatment of MTX, the number of Treg was increased (P<0.05) and Foxp3 mRNA level was up-regulated (P<0.01). 2) Typical psoriasis-like skin lesions, such as red scaly skin plaque were found after topical application of IMQ. Both the number of Treg in the splenic lymphocytes of mice and the Foxp3 mRNA level of Treg were reduced by IMQ (P<0.01 and P<0.05). 3) Different doses of MTX for mice showed the ability to improve skin lesion, increase the number of Treg in the spleen of mice and Foxp3 mRNA level in psoriatic dermatitis of mice (P<0.05).
 Conclusion: MTX is able to regulate the number of Treg and Foxp3 mRNA expression in psoriasis.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Imunossupressores/farmacologia , Metotrexato/farmacologia , Psoríase/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Adjuvantes Imunológicos/farmacologia , Aminoquinolinas/farmacologia , Animais , Estudos de Casos e Controles , Feminino , Humanos , Imiquimode , Imunossupressores/administração & dosagem , Contagem de Linfócitos , Metotrexato/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/imunologia , Psoríase/metabolismo , Psoríase/patologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Baço/citologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo
20.
Oncol Lett ; 15(5): 7279-7290, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731886

RESUMO

Vacuolar H+-ATPase (V-ATPase) serves a key role in adjusting and maintaining the intracellular pH, as well as in regulating the drug resistance of tumor cells. In recent years, the expression level of V-ATPase has been considered to be able to predict the sensitivity of breast cancer cells to chemotherapy drugs. Cluster of differentiation 147 (CD147) is known to serve a key role in the development and progression of breast cancer. The present study aimed to identify the role CD147 and V-ATPase in chemoresistance in breast cancer, and to characterize the regulation of CD147 on V-ATPase. Firstly, the expression levels of CD147 and V-ATPase were detected in chemotherapy-resistance breast cancer samples. It was demonstrated that V-ATPase was highly expressed in chemotherapy-resistance breast cancer samples, and that its expression was correlated with CD147 expression. Subsequently, MCF-7 and MDA-MB-231 cells were used to study the regulatory effect of CD147 on the expression and function of V-ATPase. Gene transfection or small interfering RNA transfection were used to control the expression of CD147 in the two cell lines. The results revealed that the overexpression of CD147 increased the expression of V-ATPase in MCF-7 cells, whereas CD147 knockdown decreased V-ATPase expression in MDA-MB-231 cells. It was also observed that CD147 affected the V-ATPase activity, regulating the transmembrane pH gradient of cancer cells. These results demonstrated that CD147 was associated with the sensitivity of chemotherapeutic drugs of epirubicin and docetaxel, while pantoprazole was able to partially reverse the CD147-mediated chemoresistance in breast cancer. Therefore, the current study provided a possible mechanism for further examination of drug resistance in breast cancer.

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