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Hemangioma is a common benign tumour that usually occurs on the skin of the head and neck, particularly among infants. The current clinical treatment against hemangioma is surgery excision, however, application of drug is a safer and more economical therapy for children suffering from hemangioma. As a natural sulfated polysaccharide rich in brown algae, fucoidan is widely recognized for anti-tumour bioactivity and dosage safety in humans. This study aims to demonstrate the anti-tumour effect and underlying mechanism of fucoidan against hemangioma in vivo and in vitro. We investigated the effects of fucoidan by culturing hemangioma cells in vitro and treating BALB/c mice bearing with hemangioma. At first, we measured the cell proliferation and migration ability through in vitro experiments. Then, we tested the expression of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathway-related biomarkers by western blot and qPCR. Furthermore, we applied ß-catenin-specific inhibitor, XAV939, to determine whether fucoidan suppressed EMT via the Wnt/ß-catenin pathway in hemangioma cells. In vivo experiments, we applied oral gavage of fucoidan to treat EOMA-bearing mice, along with evaluating the safety and efficacy of fucoidan. We found that fucoidan remarkably inhibits the proliferation and EMT ability of hemangioma cells, which is dependent on the Wnt/ß-catenin pathway. These results suggest that fucoidan exhibits tumour inhibitory effect on aggressive hemangioma via regulating the Wnt/ß-catenin signalling pathway both in vitro and in vivo, providing a new potent drug candidate for treating hemangioma.
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Hemangioma , Polissacarídeos , Via de Sinalização Wnt , beta Catenina , Animais , Criança , Humanos , Camundongos , beta Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Hemangioma/tratamento farmacológico , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Atopic dermatitis (AD) is a kind of chronic skin disease with inflammatory infiltration, characterized by skin barrier dysfunction, immune response dysregulation, and skin dysbiosis. Thymic stromal lymphopoietin (TSLP) acts as a regulator of immune response, positively associated with AD deterioration. Mainly secreted by keratinocytes, TSLP interacts with multiple immune cells (including dendritic cells, T cells, and mast cells), following induction of Th2-oriented immune response during the pathogenesis of AD. This article primarily focuses on the TSLP biological function, the relationship between TSLP and different cell populations, and the AD treatments targeting TSLP.
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Dermatite Atópica , Linfopoietina do Estroma do Timo , Humanos , Citocinas , Queratinócitos , Pele/patologiaRESUMO
D-mannose is a C-2 epimer of glucose, widely distributed in nature. Atopic dermatitis (AD) is a chronic inflammatory disease characterized by repetitious itching. The present study aimed to explore the protective effect and the underlying mechanism of D-mannose against the development of atopic dermatitis. We tested the effect of D-mannose by establishing DNCB (2,4-dinitrochlorobenzene)-induced AD mice models in vivo and culturing keratinocytes (HaCaT and NHEK) in vitro. The skin lesion severity was evaluated by histochemical staining. Cytokine expression levels were measured by real-time PCR and ELISA assay. The expression of the mammalian target of rapamycin (mTOR)/ nuclear transcription factor κB (NF-κB)-signaling-related molecules were determined by western blotting. Here, we found that topical supplementation of D-mannose remarkably attenuated skin lesions and recovered skin barrier function in AD mice model induced by DNCB. Furthermore, in vivo and in vitro experiments indicated that D-mannose inhibited tumor necrosis factor-α (TNF-α)-mediated increased expression of inflammatory cytokines. D-mannose also markedly downregulated TNF-α-stimulated activation of mTOR/NF-κB signaling pathway that was crucial for regulating the inflammatory condition. However, these effects were abolished by treatment with inhibitors of mTOR or NF-κB in HaCaT and NHEK. As far as we know, this is the first study uncovering the effective role of D-mannose via skin topical application. We found that D-mannose plays a regulatory role on inflammatory keratinocytes, suggesting its therapeutic utilization as a potential drug against atopic dermatitis.
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Dermatite Atópica , Manose , Animais , Humanos , Camundongos , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Dinitroclorobenzeno , Inflamação/metabolismo , Queratinócitos , Manose/uso terapêutico , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Pele/patologia , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Atopic dermatitis (AD) is a severe inflammatory skin disease caused by a combination of genetic, immune, and environmental factors. Intestinal microbiome disorders and changes in the immune microenvironment are associated with AD. We observed that gut bacterial metabolite enterolactone (ENL) was significantly reduced in AD model mice. Notably, patients with early childhood-onset AD exhibited decreased sera ENL level compared to the healthy controls, and the ENL level was negatively correlated with the SCORAD index. Secoisolariciresinol-diglycoside (SDG) is a natural dietary lignan of flaxseeds that can be converted by intestinal bacteria to ENL. Repeated applications of 2,4-dinitrochlorobenzene (DNCB) were performed on the ear and dorsal skin of mice to induce AD-like symptoms and skin lesions. Oral administration of SDG significantly decreased serum IgE levels and limited skin inflammation in the DNCB-induced AD mice. In addition, SDG treatment strongly limited the Th2 responses in AD mice. Moreover, we demonstrated that the IL-4 production was significantly suppressed by ENL under Th2 polarization conditions via the JAK-STAT6 signaling pathway in a concentration-dependent manner. We concluded that SDG and its derived metabolite ENL ameliorated AD development by reducing the Th2 immune response. These results suggested that SDG and ENL might be exploited as potential therapeutic candidates for AD treatment.
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Dermatite Atópica , Lignanas , 4-Butirolactona/análogos & derivados , Animais , Anti-Inflamatórios/farmacologia , Butileno Glicóis , Pré-Escolar , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno , Glucosídeos , Humanos , Imunidade , Lignanas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Pele/patologiaRESUMO
Cutaneous alterations are common in neonates and usually occur in the first few days of life. Most of these are transient and benign, appearing as physiological responses to birth. Skin pigmentation disorders are considered transitory dermatoses of newborn infants. Nail pigmentation manifests as asymptomatic brown to bluish-black skin pigmentation over the fingers and toes in newborns. Hyperpigmentation of the distal phalanx of both hands and feet is commonly found in dark-skinned newborns, but it is rare in fair-skinned newborns and East Asian populations. We herein describe a Chinese infant with transient neonatal hyperpigmentation of the proximal nail fold.
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Hiperpigmentação , Povo Asiático , China , Dedos , Humanos , Lactente , Recém-NascidoRESUMO
BACKGROUND: Primary intramedullary melanoma is a very rare tumor, most frequently occurring in the cervical and thoracic spinal cord. CASE SUMMARY: We present a rare case in which the primary intramedullary melanoma was located in the lumbar spine. A 56-year-old man complained of progressive intermittent pain in the lumbar area. Thoracic magnetic resonance imaging showed a spinal intramedullary tumor between the L3 and S1 levels. The tumor was resected entirely, and the diagnosis of malignant melanoma was confirmed by histopathology. CONCLUSION: Primary melanoma of the spinal cord, particularly intramedullary localization, has rarely been reported in the previous literature. We describe a primary malignant melanoma of the lumbar spinal cord and discuss the challenges associated with the diagnosis.
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PURPOSE: The purpose of this study was to use a murine model of psoriasis to examine the effect of total glycosides of paeony (TGP) on psoriatic skin lesions and on the expression of vascular endothelial growth factor (VEGF) in skin lesions and blood. METHODS: A murine model of psoriasis was produced by shaving the backs of the mice and applying 5% imiquimod cream, 50 mg, to the backs of the mice once a day. Mice were killed on day 8, and skin and blood samples were obtained for histopathological examination and analysis of VEGF mRNA expression. RESULTS: By day 8 of the application of imiquimod cream, skin lesions characteristic of psoriasis were evident, and histopathological examination of skin sections showed changes consistent with psoriasis (corneum thickening and parakeratosis, attenuation of the stratum granulosum, thickening of the stratum spinosum, and lengthening of the epidermal ridge). In the treatment group, 7 days of treatment with TGP resulted in resolution of the skin lesions, and histopathological examination showed the epidermis and dermis are approximately normal, without corneum thickening, hyperkeratosis, and parakeratosis. On day 7 of treatment, skin expression of VEGF mRNA was significantly lower in the treatment group than in the group that did not receive treatment (p < 0.05). Blood VEGF mRNA expression was not different between the groups. CONCLUSION: TGP is effective for the treatment of psoriasis and may act by decreasing lesion VEGF mRNA expression.
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BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disorder leading to extensive fibrosis and microvascular injury. Macrovascular disease is well documented in other autoimmune rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. However, the link is unclear between SSc and macrovascular disease, particularly atherosclerotic cardiovascular disease (CVD). This meta-analysis aimed to investigate the association between SSc and CVD. METHODS: A thorough literature search was conducted in the Cochrane, Embase, Medline, and PubMed to identify all cohort studies comparing the risk of CVD with and without SSc. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular end points were calculated. The risk of bias of included studies was assessed by the Newcastle-Ottawa scale. RESULTS: Seven cohort studies with a total of 14,813 study participants were included. In a comparison of SSc patients versus non-SSc controls, the pooled HR for cardiovascular disease was 2.36 (95% CI 1.97-2.81); for peripheral vascular disease was 5.27 (95%CI 4.27-6.51); for myocardial infarction was 2.36 (95% CI 1.71-3.25); and for stroke was 1.52 (95% CI 1.18-1.96). CONCLUSION: This meta-analysis revealed that SSc was associated with an increased risk of CVD. Clinicians who manage patients with SSc should be aware of the increased cardiovascular burden and undertake preventive measures.
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Doenças Cardiovasculares/etiologia , Escleroderma Sistêmico/complicações , Estudos de Coortes , Humanos , Fatores de RiscoRESUMO
BACKGROUND: Wound healing is a complex physiological process that is crucial for reestablishing the epithelial barrier following injury. OBJECTIVE: The aim of this study was to demonstrate the efficacy of calcipotriol, a synthetic vitamin D3 analogue, in wound healing in an acute mice wound model. METHODS: An excision wound model was established in mice, and the wound healing activity of calcipotriol was evaluated. Human keratinocyte cell lines, HaCaT and NHEK, were utilized in in vitro skin wound healing model. Cytokine expression levels were measured by real-time PCR and ELISA assay. The expression of epithelial-mesenchymal transition (EMT)-associated molecules and the phosphorylation of Yes-associated protein (YAP) was determined by western blotting. RESULTS: The increase in re-epithelialization by calcipotriol treatment early in the wound was associated with the EMT process. A scratch assay using HaCaT and NHEK cells also showed that calcipotriol administration resulted in effective wound closure. We demonstrated that calcipotriol promoted keratinocyte migration by interfering with the Hippo pathway. Calcipotriol-mediated enhancement of cell migration is related to downregulated phosphorylation of YAP and increased levels of YAP and PDZ-binding motif (TAZ). Mechanistically, we defined that calcipotriol facilitated the crosstalk between the YAP/TAZ and TGF-ß/Smad signaling pathways, eliciting EMT in keratinocytes during the wound healing process. CONCLUSIONS: These results suggest that the positive effect of calcipotriol on keratinocyte migration is mediated by the induction of EMT via the regulation of Hippo pathway, which promotes the acceleration of wound closure.
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Calcitriol/análogos & derivados , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Reepitelização/efeitos dos fármacos , Pele/lesões , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Calcitriol/farmacologia , Proteínas de Ciclo Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Células HaCaT , Via de Sinalização Hippo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Queratinócitos , Masculino , Camundongos , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Fatores de Transcrição/metabolismo , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAPRESUMO
Psoriasis is a chronic immune-mediated inflammatory cutaneous disorder with Th17 cells and Th17-related cytokines playing an important role in its development. 2'-FL (2'-fucosyllactose), which makes up about 30% of all HMOs (human milk oligosaccharides) in blood type secretor positive maternal milk, plays an essential role in supporting aspects of immune development and regulation. To explore the immunomodulatory effect of 2'-FL in psoriasis, we employed the imiquimod (IMQ)-induced psoriasis-like mouse model. Our data showed that mice administered with 2'-FL exhibited attenuated skin damage and inflammation, characterized by significantly decreased erythema and thickness and reduced recruitment of pro-inflammatory cytokines, when compared to control mice. The alleviated skin inflammation in 2'-FL treated mice was associated with a reduced proportion of Th17 cells and decreased production of Th17-related cytokines. Furthermore, we have demonstrated that 2'-FL reduced the phosphorylation of STAT3 in the skin tissue from mice with IMQ stimulation, which could account for the decreasing recruitment of Th17 cells. In vitro studies showed that 2'-FL inhibited differentiation of Th17 cells, phosphorylation of STAT3, and RORγt mRNA levels in T cells under Th17 polarization. Our results indicate that 2'-FL ameliorates IMQ-induced psoriasis by inhibiting Th17 cell immune response and Th17-related cytokine secretion via modulation of the STAT3 signaling pathway.
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Anti-Inflamatórios/uso terapêutico , Psoríase/tratamento farmacológico , Trissacarídeos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Citocinas/imunologia , Feminino , Imiquimode , Camundongos Endogâmicos C57BL , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Psoríase/induzido quimicamente , Psoríase/imunologia , Psoríase/patologia , Fator de Transcrição STAT3/imunologia , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Trissacarídeos/farmacologiaRESUMO
BACKGROUND: Current guidelines recommend local excision margin (EM) with 1 to 2 cm on primary Merkel cell carcinoma (MCC) sites. OBJECTIVE: We compared survival outcomes of patients with MCC who were treated with different surgical interventions. METHODS: A retrospective analysis of MCC cases in the Surveillance, Epidemiology, and End Results database was performed using the Kaplan-Meier, competing risk, and Cox proportional hazards regression model analyses. Influence of age, T stage, American Joint Committee on Cancer stage, adjuvant radiotherapy, and other subgroups were also analyzed by pairwise log rank test. RESULTS: Our results indicated a significant association between local destruction method and inferior survival, while an EM >2 cm showed significantly higher overall survival. In addition, the competing risk analysis depicted a similar trend as the Kaplan-Meier analysis, and considerably reduced estimated cumulative incidence. Further subgroup pairwise analysis demonstrated that the EM >2 cm method had better survival in patients who were <60 years of age, having smaller tumor diameters (T1 and T2) or having undergone adjuvant radiotherapy (P < .05). In contrast, different EMs did not show any significant association with survival rate in patients ≥75 years of age or stage III tumors. LIMITATIONS: This study was not prospectively randomized without relapse data. CONCLUSIONS: It is challenging to make optimal EM recommendations, because surgical options may depend on individual case situations. Further prospective randomized studies are warranted.
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Carcinoma de Célula de Merkel/mortalidade , Carcinoma de Célula de Merkel/cirurgia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/patologia , Procedimentos Cirúrgicos Dermatológicos , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Psoriasis is a chronic, relapsing inflammatory skin disorder. Numerous experimental evidence and therapeutic evidence have shown that the innate immune response is critical for the pathogenesis and development of psoriasis. Mannan-binding lectin (MBL), a prototypic pattern recognition molecule of the innate immune system, plays an essential role in the host defense against certain infections and also appears to be a major regulator of inflammation. In this study, we investigated the function of MBL on the course of experimental murine imiquimod (IMQ)-induced psoriasis. Our data showed that MBL-deficient (MBL-/- ) mice exhibited attenuated skin damage characterized by greatly decreased erythema compared with wild-type control mice during the early stages of IMQ-induced psoriasis-like skin inflammation. The reduced skin inflammation in MBL-/- mice was associated with the decreased infiltration of neutrophils. Furthermore, we have determined that MBL deficiency limited the chemokine CXCL1 production from skin keratinocytes upon IMQ stimulation, which might be responsible for the impaired skin recruitment of neutrophils. Additionally, we have provided the data that MBL protein promotes the IMQ-induced expression of CXCL1 and activation of MAPK/NF-κB signalling pathway in human keratinocyte HaCaT cells in vitro. In summary, our study revealed an unexpected role of MBL on keratinocyte function in skin, thus offering a new insight into the pathogenic mechanisms of psoriasis.
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Quimiocina CXCL1/biossíntese , Quimiotaxia de Leucócito , Queratinócitos/metabolismo , Lectina de Ligação a Manose/fisiologia , Neutrófilos/fisiologia , Psoríase/imunologia , Animais , Linhagem Celular Transformada , Quimiocina CXCL1/genética , Derme/imunologia , Derme/patologia , Feminino , Humanos , Imiquimode/toxicidade , Inflamação , Queratinócitos/efeitos dos fármacos , Lectina de Ligação a Manose/deficiência , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/imunologia , Lectina de Ligação a Manose/farmacologia , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/imunologia , Camundongos , Camundongos Knockout , Psoríase/induzido quimicamente , Psoríase/metabolismo , Organismos Livres de Patógenos Específicos , Regulação para CimaRESUMO
Purpose: Melanoma is the most aggressive and life-threatening cutaneous cancer. To explore new treatment strategies, it is essential to identify the mechanisms underlying melanoma tumorigenesis and metastasis. Methods: In the current study, we demonstrated altered expression of long non-coding RNA (lncRNA) and messenger RNA (mRNA) in melanoma using data from the Cancer Genome Atlas (TCGA) database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) analyses were conducted. We also constructed a functional lncRNA-mRNA regulatory network and Kaplan-Meier analysis. Results: We identified 246 differentially expressed (DE) lncRNAs and 856 DEmRNAs. A total of 184 DElncRNAs and 428 DEmRNAs were upregulated in metastatic melanoma, while all others were downregulated. Additionally, we investigated the co-expression pattern of 363 genes, among which 26 upregulated lncRNAs, 9 down- regulated lncRNAs, 49 upregulated mRNAs and 151 downregulated mRNAs were identified as being co-expressed with others. Survival analysis suggested high levels of 14 lncRNAs and 10 mRNAs may significantly increase or decrease overall survival. These differentially expressed genes are also potentially prognostic in melanoma. Conclusion: Our findings observe potential roles for lncRNAs and mRNAs during melanoma progression and provide candidate biomarkers for further studies.
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Atopic dermatitis (AD) is a common chronic inflammatory skin disease that is often associated with skin barrier dysfunction leading to a higher frequency of bacterial and viral skin infections. Toll-like receptor (TLR) 4 on resident skin cells was involved in sensing pathogens and eliciting pathogen-specific innate and adaptive immune responses. Previous studies have demonstrated that TLR4 was linked to AD severity in context of pathogen infection. However, the immune regulatory role of TLR4 in AD remains to be defined. We here investigated the immune regulatory function of TLR4 in AD induced by repeated epicutaneous application of a hapten, 2,4-dinitrochlorobenzene (DNCB). Our results showed that TLR4-deficient (TLR4-/- ) mice exhibited more severe AD symptoms than WT mice after DNCB challenge. The DNCB-treated TLR4-/- mice also displayed higher expression levels of inflammatory cytokines and stronger Th2 response than WT counterparts. Moreover, the skin expression of thymic stromal lymphopoietin (TSLP), an important potential contributor to allergic inflammation, was significantly elevated in TLR4-/- mice compared with that in WT mice upon DNCB administration. Furthermore, we demonstrated that the migration of langerin-positive dendritic cells (DCs) into draining lymph nodes was enhanced in TLR4-/- mice following DNCB challenge, which is partially dependent on the production of pro-inflammatory cytokine TNF-α. Together, these results determined that TLR4 affected the hapten-induced skin inflammation in the absence of exogenous pathogen infection, suggesting that TLR4 not only regulates infection but also may serve as a modulator of the immune response during AD development.
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Movimento Celular , Citocinas/genética , Células Dendríticas/fisiologia , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Receptor 4 Toll-Like/imunologia , Animais , Antígenos de Superfície/metabolismo , Citocinas/metabolismo , Células Dendríticas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Eosinófilos/imunologia , Feminino , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Mastócitos/imunologia , Camundongos , Camundongos Knockout , RNA Mensageiro/metabolismo , Células Th1/imunologia , Células Th2/imunologia , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Linfopoietina do Estroma do TimoRESUMO
The main aim of this study is to investigate the underlying relationship shared between microRNA-200a (miR-200a) and its link to concentrations of Th17 and Treg cells, mRNA expressions of their specific transcription factors retinoic acid-related orphan receptor γt (RORγt) and head box protein 3 (FOXP3) and relevant cytokines in patients with psoriasis vulgaris (PV). A total of 189 patients previously diagnosed with PV were selected as the experimental group, whilst 109 healthy individuals as the control group. According to the psoriasis area and severity index (PASI), subjects in the experimental group were assigned into the severe group (95 cases) and the moderate group (94 cases). CD4+ T and Th17/Treg cells were extracted. MiR-200a expression and RORγt and FoxP3 mRNA expressions were detected by qRT-PCR. Concentrations of Th17 and Treg cells were measured via flow cytometry. ELISA was conducted for serum IL-17, IL-23 and TGF-ß levels. Correlation analysis was completed in accordance with the Pearson method. Compared with the moderate group, higher miR-200a expression, RORγt mRNA expression, percentage of Th17, Th17/Treg ratio and levels of IL-17 and IL-23 exhibited in the severe group, whilst FoxP3 mRNA expression and, percentage of Treg as well as TGF-ß were lower. A same trend displayed when comparing the moderate group to the control group. We found that miR-200a expression, percentage of Th17, Th17/Treg ratio, IL-17 and IL-23 levels and RORγt mRNA expression are positively correlated with PASI grade, while the percentage of Treg, TGF-ß level and FoxP3 mRNA expression are negatively correlated with PASI grade. The results also displayed that the percentage of Th17, Th17/Treg ratio, IL-17 and IL-23 levels and RORγt mRNA expression are positively correlated with miR-200a expression, while the percentage seen in Treg and TGF-ßand FoxP3 mRNA expression are negatively correlated with miR-200a expression. Our results provided a strong evidence that up-regulation of microRNA-200a in CD4+ T cells may induce immune dysfunction through Th17/Treg cells and relevant cytokines in PV patients.
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Linfócitos T CD4-Positivos/metabolismo , Citocinas/metabolismo , MicroRNAs/metabolismo , Psoríase/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima/fisiologiaRESUMO
Acitretin has been a valuable option for the treatment of psoriasis, however, the molecular events of acitretin leading to the normalization of keratinocytes differentiation on psoriasis patients have not been fully explored. To investigate whether there were certain relationship between keratinocytes proliferation and JAK/STAT signaling pathways in psoriasis, and how acitretin modulated the signaling pathways. HaCaT cells, an in vitro immortal human keratinocyte cell line, was chosen as a in vitro model of psoriasis. The small interfering RNA targeting STAT1 (siRNA-STAT1) and STAT3 (siRNA-STAT3) were subsequently transfected into the HaCaT cells which were treated with or without acitretin. We found that HaCaT cells proliferation and the expression of STAT1 or STAT3 were inhibited by acitretin, siRNA-STAT1 and siRNA-STAT3. Our experimental data shows that acitretin might inhibit HaCaT cells proliferation in psoriasis by decreasing the expression of STAT- and STAT3-dependent mechanism.
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Atopic dermatitis (AD) is a common inflammatory skin disease with high rates of morbidity and is associated with erythema, pruritus, scaling of affected areas of skin. It is extremely important to introduce a therapeutic agent which has significant anti-inflammatory effect with less side-effect for treatment of AD. This study evaluated the effect of a natural compound from herbal extracts, the crude polysaccharide extracted from the white wax scale (CWPS), on AD-like mice. Repeated applications of 2,4-dinitrochlorobenzene (DNCB) were performed on ear and dorsal skin of BALB/c mice to induce AD-like symptoms and skin lesions. Oral administration of CWPS decreased serum IgE level and limited the infiltration of mast cells and eosinophils to the dermal tissues in the DNCB-induced AD mice. In addition, CWPS reduced Th1 and Th17 responses, leading to an attenuated cutaneous inflammatory response. Furthermore, in vitro study also demonstrated that CWPS limited T cell activation and cytokines (i.e. IFN-γ and IL-17) production induced by DNCB. We conclude that CWPS attenuates DNCB-induced AD-like skin lesion through modulating T cell-elicited immune responses and CD4+ T cell polarization, and could be exploited as a new therapeutic approach for AD.
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Psoriasis is an autoimmune disease, which is characterized by aberrantly high levels of inflammation, but the underlying pathogenic mechanisms are still not fully understood. Signal transducer and activator of transcription 1 (STAT1) and STAT3, and the downstream proteins suppressor of cytokine signaling 1 (SOCS1) and SOCS3, have been implicated in psoriasis disease progression. Calcipotriol, a synthetic derivative of vitamin D, has been used clinically to treat psoriasis, but the mechanism of action that underlies the beneficial effects of calcipotriol is still being explored. The objective of this study was to determine whether STAT1 and STAT3 signaling is involved in calcipotriol treatment. Using an in vitro immortal human keratinocyte cell line, HaCaT cells, as a psoriasis model, we examined the molecular signaling induced by calcipotriol treatment. We found that calcipotriol treatment or silencing of either STAT1 or STAT3 inhibited proliferation of HaCaT cells. Calcipotriol downregulated the expression of STAT1 and STAT3 at the messenger RNA (mRNA) and protein levels. The levels of phosphorylated STAT1 and STAT3 were also decreased, suggesting calcipotriol treatment inhibited STAT1 and STAT3 activation. Calcipotriol-mediated STAT inhibition was further substantiated by the downregulation of SOCS1 and SOCS3 at the mRNA and protein expression levels. Taken together, our results suggest a novel molecular mechanism for calcipotriol-mediated treatment effects in psoriasis.
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Calcitriol/análogos & derivados , Regulação para Baixo/efeitos dos fármacos , Queratinócitos/citologia , Queratinócitos/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Calcitriol/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT3/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
A 76-year-old woman has got both lower limbs petechia and ecchymosis for 1 month, edema for 6 days and fever for 3 days. The patient suffered from purpura of both lower limbs, edema, arthralgia, recurrent fever, kidney damages, serositis, progressive reduction of platelet, moderate anemia and lymphadenopathy during the last two months. Laboratory examinations showed that her whole blood cells, platelet counts, serum albumin level and complements were all decreased and her titres of antibodies to double-stranded DNA (ds-DNA) were high. The patient had unequivocal SLE as she fulfilled seven American Rheumatism Association criteria (1997). Enzyme linked immunosorbent assays (ELISAs) for human immunodeficiency virus (HIV) was positive, while negative by Western blot analysis. A diagnosis of Systemic lupus erythematosus was made in view of the above findings. Because of the presence of autoantibodies and cross-reactivity, diagnosis of HIV infection should be cautious in patients with systemic autoimmune disease. The use of rigorous confirmatory testing by western blot analysis or immunofluorescence assay is therefore mandatory. More sensitive assays may be necessary to confirm the presence of HIV infection, such as gene amplification by the polymerase chain reaction, virus isolation and cultivation, the CD4 cell count and the ratio of CD4/CD8.
Assuntos
Infecções por HIV/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Idoso , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Reações Falso-Positivas , Feminino , HumanosRESUMO
BACKGROUND: Amphotericin B (AMB) is a polyene antibiotic with broad spectrum antifungal activity, but its clinical toxicities and poor solubility limit the wide application of AMB in clinical practice. Recently, new drug-loaded nanoparticles (NPs) - diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (PLGA-TPGS) - have received special attention for their reduced toxicity, and increased effectiveness of drug has also been reported. This study aimed to develop AMB-loaded PLGA-TPGS nanoparticles (AMB-NPs) and evaluate their antifungal effects in vitro and in vivo. METHODS: AMB-NPs were prepared with a modified nanoprecipitation method and then characterized in terms of physical characteristics, in vitro drug release, stability, drug-encapsulation efficiency, and toxicity. Finally, the antifungal activity of AMB-NPs was investigated in vitro and in vivo. RESULTS: AMB-NPs were stable and spherical, with an average size of around 110 nm; the entrapment efficacy was closed to 85%, and their release exhibited a typically biphasic pattern. The actual minimum inhibitory concentration of AMB-NPs against Candida albicans was significantly lower than that of free AMB, and AMB-NPs were less toxic on blood cells. In vivo experiments indicated that AMB-NPs achieved significantly better and prolonged antifungal effects when compared with free AMB. CONCLUSION: The AMB-PLGA-TPGS NP system significantly improves the AMB bioavailability by improving its antifungal activities and reducing its toxicity, and thus, these NPs may become a good drug carrier for antifungal treatment.