Separation, characterization and anti-psoriasis effect of self-assembled nanoparticles from Shaoyao Gancao Decoction / 中国中药杂志

This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.

Abordagens terapêuticas do Condiloma Acuminado em crianças e adolescentes / Therapeutic approaches to Condyloma Acuminatum in children and adolescents

Objetivos: A infecção pelo papiloma vírus humano dos tipos 6 e 11 pode evoluir para Condiloma Acuminado. Sua transmissão é principalmente via sexual, de forma que a presença dessas verrugas em crianças deve ser consi-derada sinal de alarme para investigação de abuso. Eventualmente, contudo, ocorre por autoinoculação ou fômites. O tratamento é desafiador, dado que apesar do extenso arsenal, a recorrência se faz comum. A presente revisão siste-mática advém a comparar taxas de sucesso das estratégias terapêuticas, objetivando fornecer substrato para escolhaacertada no tratamento da doença em crianças e adolescentes. Métodos: Foi realizada Revisão Sistemática baseada no GuidelinePreferred Report Items for Systematic Reviews and Meta-Analyses (PRISMA), registrada na Plataforma PROSPERO sob identificação CRD42021262090. Resultados: 211 estudos foram encontrados nasdatabases con-sultadas, de forma que 30 atenderam as propostas de critérios estabelecidos na pesquisa sistematizada. Esses pas-saram extração de dados para síntese qualitativa, demonstrando eficácia de métodos não-invasivos a invasivos.Conclusões: Mediante bons resultados em resolução da doença e reduzidos efeitos adversos, a terapia mais popular entre os autores foi o Imiquimode. A pesquisa chamou atenção à necessidade de estudos mais robustos e metodo-logias mais complexas acerca das abordagens terapêuticas do Condiloma Acuminado em crianças e adolescentes. (AU)

Objectives: Infection with human papillomavirus types 6 and 11 can progress to Condyloma acuminata. Its transmission is mainly sexual, so these warts in children should be considered an alarm signal for abuse investigation. Eventually, however, it occurs by autoinoculation or fomites. Treatment is challenging, given that despite the extensive arsenal, recurrence is common. The present systematic review compares the success rates of therapeutic strategies, aiming to provide a substrate for the right choice in the treatment of the disease in children and adolescents. Methods: Asystematic review was performed based on the guideline for Preferred Report Items for Systematic Reviews and Meta-Analyses (PRISMA), registered on the PROSPERO Platform under identification CRD42021262090. Results: 211 studies were found in thedatabasesconsulted, and 30 met the proposed criteria established in the systematic research. These passed data extraction for qualitative synthesis, demonstrating the effectiveness of non-invasive to invasive methods. Conclusions: Due to good results in disease resolution and reduced adverse effects, the most popular therapy among the authors was Imiquimod. The research called attention to the need for more robust studies and more complex methodologies about the therapeutic approaches of Condyloma Acuminatum in children and adolescents. (AU)

Impacto Terapêutico da Associação do Uso de Imiquimode e Criocirurgia no Tratamento de Verrugas Subungueais e Periungueais: Relato de Caso / Therapeutic Impact of the Association of Imiquimod Use and Cryosurgery in the Treatment of Subungual and Periungual Warts: Case Report

Introdução: Habitualmente, as verrugas virais são causadas pelo papilomavírus humano (HPV) e, embora tenham tendência à resolu- ção espontânea, quando crônicas, conferem resistência terapêutica. Objetivo: Divulgar um caso de sucesso terapêutico da associação do uso de imiquimode e criocirurgia para verrugas virais periungueais e subungueais. Relato do caso: O relato é de um homem de 56 anos, com cinco anos de evolução de verrugas subungueais e periungueais distribuídas na maioria dos dedos das mãos. Anteriormente, foi tratado com antifúngicos pelo resultado micológico, sem sucesso. Foi submetido à biópsia subungueal, cujo anatomopatológico confirmou verruga plana. Foi proposto o tratamento combinado de imiquimode creme 5% e criocirurgia. Evoluiu com resolução completa das lesões virais. Conclusão: Os autores demonstram a importância dos achados anatomopatológicos no diagnóstico de verrugas virais recalcitrantes, bem como é ressaltada a eficácia da associação do uso de imiquimode e criocirurgia.

Introduction: Viral warts are usually caused by the human papillomavirus (HPV), and although they tend to resolve spontaneously, when chronic, they confer therapeutic resistance. Aim: To report a case of therapeutic success of imiquimod and cryosurgery combination for periungual and subungual viral warts. Case Report: The report is of a 56-year-old man with five years of evolution of subungual and periungual warts distributed on most fingers of the hands. Previously, he received treatment with antifungal drugs due to the mycological result, but it was unsuccessful. He underwent a subungual biopsy, whose pathology confirmed the flat wart. A combined treatment of imiquimod cream 5% and cryosurgery was proposed. The patient evolved with complete resolution of the viral lesions. Conclusion: The authors demonstrate the importance of pathological findings in the diagnosis of recalcitrant viral warts, as well as the efficacy of the association of imiquimod and cryosurgery.

Effect of fire needling on imiquimod induced psoriasis-like lesion and STAT3 pathway in mice / 中国针灸

OBJECTIVE@#To observe the effect of fire needling on psoriasis-like lesion and the signal transducer and activator of transcription 3 (STAT3) pathway in mice and compare the therapeutic effect between different interventions of fire needling therapy (surrounding technique of fire needling, fire needling at "Dazhui" [GV 14] and "Zusanli" [ST 36]).@*METHODS@#Thirty male BALB/c mice were randomized into a blank group, a model group, a dexamthasone group, a surrounding technique group and an acupoint group, 6 mice in each one. Except the blank group, the mice in the rest groups were established as psoriasis-like lesion model by topical application with imiquimod cream, once daily, consecutively for 8 days. From day 4 to day 8, in the dexamthasone group, gastric infusion with 0.2 mL dexamthasone was administered, once daily. On day 4, 6 and 8, in the surrounding technique group, fire needling was exerted around the skin lesion; and fire needling was applied to "Dazhui" (GV 14) and "Zusanli" (ST 36) in the acupoint group, once a day. The changes in skin lesion on the dorsal parts of mice were observed in each group to score the psoriasis area and severity index (PASI). Using HE staining, the dermal morphological changes and epidermal thickness were observed in the mice of each group. The positive expression of proliferating cell-associated antigen Ki-67 was determined by immunofluorescence. Immunohistochemistry method was used to determine the expressions of , and T cells of skin tissue in each group. Using real-time PCR, the expressions of interleukin (IL)-17, IL-22, tumor necrosis factor α(TNF-α) mRNA were determined. Western blot method was adopted to determine the protein expressions of STAT3 and p-STAT3 in skin tissue in each group.@*RESULTS@#Compared with the blank group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all increased in the mice of the model group (P<0.01). Except for the erythema scores of the dexamethasone group and the surrounding technique group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all decreased in each intervention group as compared with the model group (P<0.01). The infiltration scores and the total scores in the dexamethasone group and the acupoint group were lower than those in the surrounding technique group respectively (P<0.01, P<0.05). In comparison with the blank group, Ki-67 positive cell numbers and the numbers of , and T cells in skin tissue were increased in the mice of the model group (P<0.01). Ki-67 positive cell numbers and the numbers of , and T cells were reduced in each intervention group as compared with the model group (P<0.01), and the numbers of and T cells in the acupoint group were less than the surrounding technique group (P<0.01). Compared with the blank group, the mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all increased in the model group (P<0.01). The mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all decreased in each intervention group as compared with the model group (P<0.01, P<0.05). The mRNA expressions of IL-17, IL-22 and TNF-α in the acupoint group, as well as mRNA expression of IL-17 in the surrounding technique group were all lower than the dexamethasone group (P<0.01), while, the mRNA expression of IL-22 in the acupoint group was lower than the surrounding technique group (P<0.01).@*CONCLUSION@#Fire needling therapy improves skin lesion severity in imiquimod induced psoriasis-like lesion of the mice, which is probably related to the inhibition of STAT3 pathway activation and the decrease of Th17 inflammatory factors expression. The systemic regulation of fire needling at "Dazhui" (GV 14) and "Zusanli" (ST 36) is superior to the local treatment.

Effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice / 中国针灸

OBJECTIVE@#To observe the effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice, and to explore the possible mechanism of moxibustion for psoriasis.@*METHODS@#A total of 32 male BALB/c mice were randomly divided into a normal group, a model group, a moxibustion group and a medication group, 8 mice in each group. Psoriasis model was induced by applying 5% imiquimod cream on the back for 7 days in the model group, the moxibustion group and the medication group. At the same time of model establishment, the moxibustion group was treated with suspension moxibustion on skin lesions on the back, 20 min each time, once a day; the medication group was treated with 1 mg/kg methotrexate tablet solution by gavage, once a day. Both groups were intervened for 7 days. The daily changes of skin lesions were observed, and the psoriasis area and severity index (PASI) score was evaluated; the histopathological changes of skin lesions were observed by HE staining; the positive expression of proliferating cell nuclear antigen (PCNA) and T lymphocyte surface marker CD3 were detected by immunohistochemistry; the expression level of serum interleukin (IL) -17A was detected by ELISA, and the relative expressions of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 mRNA in skin lesions were detected by real-time PCR.@*RESULTS@#The increased and hypertrophy scale, dry skin, red and swollen epidermis and obvious infiltration were observed in the model group, and each score and total score of PASI were higher than those in the normal group (P<0.01). The scale score, infiltration score, and total score of PASI in the moxibustion group were lower than those in the model group (P<0.01); the infiltration score and total score of PASI in the medication group were lower than those in the model group (P<0.01, P<0.05). The inflammatory cell infiltration in the model group was obvious, and the thickness of epidermal layer was increased compared with that in the normal group (P<0.01); the inflammatory cell infiltration and Munro micro abscess were decreased in the moxibustion group and the medication group, and the thickness of epidermal layer was decreased compared with that in the model group (P<0.01). Compared with the normal group, the positive cell number of PCNA and T was increased (P<0.01), and the body mass was decreased, and the spleen index was increased (P<0.01), and the expression of serum IL-17A and the relative expression of TNF-α, IL-1β and IL-6 mRNA in the skin lesions was increased in the model group (P<0.01). Compared with the model group, the positive cell number of PCNA and T was reduced (P<0.01), and the spleen index and the relative expression of TNF-α, IL-1β and IL-6 mRNA were reduced (P<0.01) in the moxibustion group and the medication group; the body mass of mice in the moxibustion group was higher than that in the model group (P<0.01); the content of serum IL-17A in the medication group was lower than that in the model group (P<0.01); the relative expression of TNF-α, IL-1β mRNA in the moxibustion group was higher than that in the medication group (P<0.01).@*CONCLUSION@#Moxibustion could effectively improve the scale and infiltration of skin lesions in psoriasis mice. Its mechanism may be related to inhibiting inflammatory response and regulating immunity.

Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61 / 中西医结合学报

OBJECTIVE@#Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.@*METHODS@#The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.@*RESULTS@#Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.@*CONCLUSION@#The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

Case of large lentigo maligna melanoma of the scalp treated with 5% and 3. 75% Imiquimod

Abstract The paper presents a case of lentigo maligna melanoma of the scalp in an elderly patient treated for the nodular part with surgery and the residual melanoma in situ with 5% Imiquimod and subsequently with 3.75% Imiquimod (each concentration for 4 months, 5 times per week), with complete regression of the lesion. 3.75% Imiquimod, which is already used for the treatment of actinic keratosis, could be a useful weapon with the same effectiveness and fewer side effects compared to 5% Imiquimod.

Tratamiento no quirúrgico, quirúrgico y reconstructivo del carcinoma basal de párpados / Non-surgical, surgical and reconstructive treatment of basal cell eyelid carcinoma

Se realizó una búsqueda sobre carcinoma basal de párpado, con el objetivo de describir el contexto actual del tratamiento quirúrgico, no quirúrgico y reconstructivo. Con el fin de eliminar el tumor con las menores secuelas funcionales y estéticas posibles, son aceptadas muchas opciones de tratamiento en el manejo actual de esta patología, que incluyen: tratamientos tópicos (imiquimod, interferones, vismodegib, sonidegib), procedimientos mínimamente invasivos (terapia fotodinámica), modalidades ablativas (curetaje, electrocauterización, criocirugía) y procedimientos altamente especializados (resección quirúrgica convencional, radioterapia o cirugía de Mohs). El tratamiento previo, el subtipo histológico, el sitio y el tamaño de la lesión deben considerarse en la planificación quirúrgica, porque se ha demostrado que afectan las tasas de curación. A partir de estos elementos, se desarrolló un algoritmo para el tratamiento del carcinoma basocelular que podría ayudar a elegir la técnica quirúrgica y los márgenes de seguridad, especialmente en lugares donde la cirugía micrográfica no está ampliamente disponible(AU)

A bibliographic search was conducted about basal eyelid carcinoma with the purpose of describing the current context of surgical, non-surgical and reconstructive treatment. Current management of this condition includes many treatment options aimed at removing the tumor with the least possible functional and esthetic sequels. Among them are the following: topical medication (imiquimod, interferons, vismodegib, sonidegib), minimally invasive procedures (photodynamic therapy), ablative therapy (curettage, electrocauterization, cryosurgery) and highly specialized procedures (conventional surgical resection, radiotherapy or Mohs surgery). Surgical planning should consider the previous treatment, the histological subtype, and the site and size of the lesion. These factors have been shown to affect cure rates. Based on these elements, an algorithm was developed for the treatment of basal cell carcinoma which may be useful in selecting the surgical technique and safety margins, particularly in settings where micrographic surgery is not widely available(AU)

Acné queloideo de la nuca: excelente respuesta al tratamiento con imiquimod 5% / Keloid acne of the nape: excellent response to treatment with imiquimod 5%

El acné queloideo de la nuca (AKN) o foliculitis esclerosante es un proceso inflamatorio crónico del folículo piloso en la región de la nuca. Su incidencia es baja y su etiología desconocida. Afecta con mayor frecuencia a hombres de mediana edad y de raza negra. A lo largo del tiempo se han utilizado diferentes modalidades terapéuticas con resultados variables. Presentamos el caso de un paciente con AKN que mostró una excelente respuesta al uso diario de imiquimod 5% tópico durante ocho semanas

Keloid acne of the neck (AKN) or sclerosing folliculitis of the nape of the neck is a chronic inflammatory process of the nape region. Its incidence is low and its etiology is unknown. It mainly affects brown-black males in middle age. Different treatment modalities have been used with different responses. We present the case of a patient with AKN who presented an excellent response to the daily use of topical imiquimod 5% for eight weeks

Efficacy of imiquimod 5% cream as first-line management in cutaneous leishmaniasis caused by Leishmania mexicana

Abstract Cutaneous leishmaniasis (CL) involves several differential diagnoses as it lacks a gold standard diagnostic test. Its diagnosis is easier in endemic regions; however, many cases come from travelers to endemic areas. A 22-year-old patient, who had recently visited Oaxaca, Mexico, developed two asymptomatic ulcers weeks later on the left auricle and the nose. Leishmania mexicana was identified using polymerase chain reaction. The patient was treated with imiquimod 5% cream three times/week, providing favorable results after 12 weeks, without relapse 2 months after therapy. To our knowledge, this is the first case of CL due to L. mexicana effectively treated with imiquimod.

Acantholytic pityriasis rubra pilaris associated with topical use of imiquimod 5%: case report and literature review

Abstract Topical use of immune response modifiers, such as imiquimod, has increased in dermatology. Although its topical use is well tolerated, it may be associated with exacerbations of generalized cutaneous inflammatory diseases, possibly through the systemic circulation of pro-inflammatory cytokines. This report describes a case of development of pityriasis rubra pilaris, a rare erythematous-papulosquamous dermatosis, in a woman aged 60 years during treatment with imiquimod 5% cream for actinic keratosis. It evolved with erythrodermic conditions and palmoplantar keratoderma, presenting progressive clinical resolution after the introduction of methotrexate. The authors emphasize the importance of recognizing possible systemic reactions associated with the topical use of imiquimod.

4'-O-ß-D-glucosyl-5-O-methylvisamminol ameliorates imiquimod-induced psoriasis-like dermatitis and inhibits inflammatory cytokines production by suppressing the NF-κB and MAPK signaling pathways

Psoriasis is a chronic inflammatory skin disorder in humans, and the inflammatory reaction plays an important role in development and onset of psoriasis. 4'-O-β-D-glucosyl-5-O-methylvisamminol (4GMV) is one of the major active chromones isolated from Saposhnikoviae divaricata (Turcz.) Schischk, which has been reported to exhibit excellent anti-inflammatory activities. However, the possible therapeutic effect on psoriasis and underlying mechanism has not been reported. Thus, the aim of this study was to investigate the protective effect of 4GMV on the imiquimod (IMQ)-induced psoriasis-like lesions in BALB/c mice and the anti-inflammatory effect on the lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. The results demonstrated that 4GMV decreased IMQ-induced keratinocyte proliferation and inflammatory cell infiltration. Moreover, 4GMV treatment significantly inhibited the production of NO, PEG 2, and cytokines such as interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and IL-22 in LPS-stimulated RAW264.7 macrophages. 4GMV also suppressed the LPS-upregulated protein expressions of iNOS and COX-2 in a dose-dependent manner. Furthermore, qRT-PCR analysis showed that 4GMV down-regulated the mRNA level of IL-1β and IL-6 expression. Further studies by western blot indicated that 4GMV inhibited the activation of upstream mediator NF-κB by suppressing the expression of TLR4 and the phosphorylation of IκBα and p65. The phosphorylation of JNK, p38, and ERK were also markedly reversed by 4GMV in LPS-treated RAW264.7 macrophages. Taken together, these results demonstrated that 4GMV showed a protective effect in IMQ-induced psoriasis-like mice and inhibited inflammation through the NF-κB and MAPK signaling pathways, indicating that 4GMV might be a potential therapeutic drug for psoriasis.

Small interfering RNA targeting of keratin 17 reduces inflammation in imiquimod-induced psoriasis-like dermatitis / 中华医学杂志(英文版)

BACKGROUND@#Psoriasis is a common chronic inflammatory skin disease with 2% to 3% prevalence worldwide and a heavy social-psychological burden for patients and their families. As the exact pathogenesis of psoriasis is still unknown, the current treatment is far from satisfactory. Thus, there is an urgent need to find a more effective therapy for this disease. Keratin 17 (K17), a type I intermediate filament, is overexpressed in the psoriatic epidermis and plays a critical pathogenic role by stimulating T cells in psoriasis. Therefore, we hypothesized that inhibiting K17 may be a potential therapeutic approach for psoriasis. This study aimed to investigate the therapeutic effect of K17-specific small interfering RNA (siRNA) on mice with imiquimod (IMQ)-induced psoriasis-like dermatitis.@*METHODS@#Eight-week-old female BALB/c mice were administered a 5% IMQ cream on both ears to produce psoriatic dermatitis. On day 3, K17 siRNA was mixed with an emulsion matrix and applied topically to the left ears of the mice after IMQ application every day for 7 days. The right ears of the mice were treated in parallel with negative control (NC) siRNA. Inflammation was evaluated by gross ear thickness, histopathology, the infiltration of inflammatory cells (CD3+ T cells and neutrophils) using immunofluorescence, and the expression of cytokine production using real-time quantitative polymerase chain reaction. The obtained data were statistically evaluated by unpaired t-tests and a one-way analysis of variance.@*RESULTS@#The severity of IMQ-induced dermatitis on K17 siRNA-treated mice ears was significantly lower than that on NC siRNA-treated mice ears, as evidenced by the alleviated ear inflammation phenotype, including decreased ear thickness, infiltration of inflammatory cells (CD3+ T cells and neutrophils), and inflammatory cytokine/chemokine expression levels (interleukin 17 [IL-17], IL-22, IL-23, C-X-C motif chemokine ligand 1, and C-C motif chemokine ligand 20) (P < 0.05 vs. the Blank or NC siRNA groups). Compared to the NC siRNA treatment, the K17 siRNA treatment resulted in increased K1 and K10 expression, which are characteristic of keratinocyte differentiation (vs. NC siRNA, K17 siRNA1 group: K1, t = 4.782, P = 0.0050; K10, t = 3.365, P = 0.0120; K17 siRNA2 group: K1, t = 4.104, P = 0.0093; K10, t = 4.168, P = 0.0042; siRNA Mix group: K1, t = 3.065, P = 0.0221; K10, t = 10.83, P < 0.0001), and decreased K16 expression, which is characteristic of keratinocyte proliferation (vs. NC siRNA, K17 siRNA1 group: t = 4.156, P = 0.0043; K17 siRNA2 group: t = 2.834, P = 0.0253; siRNA Mix group: t = 2.734, P = 0.0250).@*CONCLUSIONS@#Inhibition of K17 expression by its specific siRNA significantly alleviated inflammation in mice with IMQ-induced psoriasis-like dermatitis. Thus, gene therapy targeting K17 may be a potential treatment approach for psoriasis.

Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyper-proliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. METHODS: HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. RESULTS: Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. CONCLUSIONS: Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.

A case of chronic and relapsing paget disease of the vulva

Abstract Extramammary Paget disease is a rare neoplastic condition that more commonly affects postmenopausal Caucasian women. Although the vulvar area is the most frequently affected location, it corresponds solely to 1 to 2% of all vulvar malignancies. A 72-year-old female patient was observed in our outpatient clinic with a 2-year history of an erythematous and pruritic plaque on the vulva. Histopathology and immunohistochemistry studies were compatible with extramammary Paget disease of the vulva. Associated neoplastic conditions were excluded. Due to multiple relapses, the patient was submitted to three surgical interventions, including a total vulvectomy, and to external radiotherapy. The present case illustrates the chronic and recurrent nature of extramammary Paget disease despite aggressive procedures as well as the challenge in obtaining tumor-free resection margins.

Prevalencia y manejo de condilomas en población consultante en Chile: estudio "DIACON" / Prevalence and management of condylomas in consulting population in Chile: "DIACON study"

Resumen Introducción: Los condilomas o verrugas genitales (VG) son la infección de transmisión sexual (ITS) más diagnosticada en los centros de ITS en Chile, pero no existen estadísticas poblacionales. Objetivos: Describir la prevalencia de VG en pacientes de 18-60 años que acuden a consulta ambulatoria de dermatología, ginecología y urología; características demográficas de los pacientes y prácticas de diagnóstico y tratamiento. Material y Métodos: A una muestra de especialistas chilenos estratificados por región, población y sexo de pacientes se les proporcionó un diario de registro y aplicó un cuestionario. Resultados: Prevalencia VG grupo total: 2,4%; en grupo etario 18-34 años: 3,7%; en grupo etario 35-60 años: 1,29% (p = 0,0000). La edad media de los pacientes con VG fue 29,4 años en mujeres y 32,7 años en hombres (p = 0,019); la distribución por edad fue diferente según sexo y sistema de salud. La inspección visual fue el método diagnóstico más frecuente y la crema de imiquimod el tratamiento más común. Hubo diferencias en el uso de herramientas diagnósticas y terapéuticas según sexo del paciente, especialidad del médico y sistema de salud. Conclusiones: Existe una alta prevalencia de VG, que debería ser tomada en cuenta para planificar las intervenciones de salud pública para abordar este problema.

Introduction: Condylomas or genital warts (GW) are the most frequently diagnosed sexually transmitted infection (STI) in STI centers in Chile, but there are no population statistics available. Objectives: To describe the prevalence of GW in patients from 18-60 years of age who attend outpatient dermatology, gynecology and urology practice; the demographic characteristics of the patients and the diagnostic and treatment tools. Methods: A sample of Chilean specialists stratified by region, population and gender of patients was provided with a logbook and answered a questionnaire. Results: The GW prevalence was 2.44% for the whole group; 3.76% for the 18-34 age group and 1.29% for the 35-60 years group (p = 0.0000). The average age of patients with GW was 29.4 years in women and 32.7 years in men (p = 0.019). The distribution by age was different according to gender and health system. Visual inspection was the most frequent diagnostic method used and imiquimod cream the most common treatment, however, there were differences in the use of diagnostic and therapeutic tools according to the patient's gender, specialty of the doctor and health system. Conclusions: The high prevalence of GW confirmed the need and importance of public health interventions to address this problem.

Giant condylomata acuminata of Buschke-Lowenstein: Surgical method as effective treatment and Imiquimod as adjuvant therapy in an immunocompetent patient / Condiloma acuminado gigante de Buschke-Lowenstein: Método cirúrgico como tratamento eficaz e Imiquimode como terapia adjuvante em uma paciente imunocompetente

Introduction: Giant condylomata acuminata, also known as Buschke-Lowenstein tumor is a rare form of tumor of the anogenital condylomata acuminata, which is a sexually transmitted infection (STI) caused by the human papillomavirus (HPV). Objective: To report a case of giant condylomata acuminata in an immunocompetent patient. Case report: The patient was referred to the Outpatient Clinic for Sexually Transmitted Infections and AIDS at a public hospital in the city of Vitória, Espírito Santo State, Brazil, reporting the onset of progressive growth verrucous lesions on the external genitalia for four months. The patient underwent surgical ablation, and giant condylomata diagnostic confirmation was obtained through histopathology. She was treated with 5% imiquimod cream in routine applications for eight consecutive weeks to avoid recurrence and was also vaccinated for HPV after the procedure. Conclusion: Surgery excision is the treatment of choice in extensive genital condylomata lesions to exclude malignancy. Imiquimod use as adjuvant therapy for reducing recurrence seems to be adequate.

Introdução: O condiloma acuminado gigante, também conhecido tumor de Buschke-Lowenstein, é uma apresentação rara do condiloma acuminado anogenital, que é uma infecção sexualmente transmissível (IST) causada pelo papilomavírus humano (HPV). Objetivo: Relatar um caso de condiloma acuminado gigante em uma paciente imunocompetente. Relato de caso: A paciente foi encaminhada para o ambulatório de infecções sexualmente transmissíveis e AIDS de um hospital público na cidade de Vitória, Espírito Santo, Brasil, relatando o aparecimento de lesões verrucosas de crescimento progressivo na genitália externa por quatro meses. A paciente foi submetida à exérese cirúrgica e a confirmação diagnóstica de condiloma gigante foi obtida através da histopatologia. Ela foi medicada com imiquimode creme a 5% em aplicações rotineiras por oito semanas consecutivas para evitar recorrências e foi também vacinada contra o HPV após o procedimento. Conclusão: Exérese cirúrgica é o tratamento de escolha em lesões condilomatosas extensas para excluir malignidade. O uso de Imiquimode como terapia adjuvante para redução de recidivas mostrou-se adequado.

Multiple approaches to sexually transmitted infections: from diagnosis to treatment

ABSTRACT Sexually transmitted infections are mainly caused by viruses and bacteria. They are transmitted trough sexual intercourse, without a condom, with an infected individual. The anus, vagina, and mouth may become involved. This study aimed to present six clinical cases with the diagnosis of sexually transmitted infections, but in which different treatment approaches were required. This demonstrates the dynamic and unique character of the disease in each individual. That is, the behavior of sexually transmitted infections will vary not only according to its causative microorganism (virus or bacteria), but also according to the characteristics of the combination of etiologic agent and host.

RESUMO As infecções sexualmente transmissíveis são causadas, principalmente, por vírus e bactérias. Por meio do contato sexual, sem preservativo, com um indivíduo que esteja infectado. O ânus, a vagina e a boca podem se tornar órgãos acometidos. O objetivo deste trabalho é apresentar 06 casos clínicos com o diagnóstico de infecções sexualmente transmissíveis, mas que para serem tratados foram necessárias diferentes abordagens. Isso demonstra o caráter dinâmico e singular da doença em cada indivíduo. Ou seja, o comportamento das infecções sexualmente transmissíveis vai variar não somente conforme o seu microrganismo causador (vírus × bactéria), mas também de acordo com o conjunto (agente etiológico + hospedeiro).

Vegetative chronic genital herpes with satisfactory response to imiquimod

Abstract Vegetative chronic genital herpes is an atypical presentation of herpes simplex 2 that it is usually seen in patients coinfected with human immunodeficiency virus. Clinically, it is characterized by extensive ulcers that evolve to chronification and hypertrophic pseudotumor forms. Antiviral drugs are recommended for the treatment, and acyclovir is the most used one. Foscarnet is the treatment of choice to resistant cases, although treatment failure has been reported. We report a male patient, previously diagnosed with human immunodeficiency virus who developed vegetative chronic genital herpes resistant to acyclovir and successfully treated with imiquimod.

Interleukin-18 exacerbates skin inflammation and affects microabscesses and scale formation in a mouse model of imiquimod-induced psoriasis / 中华医学杂志(英文版)

BACKGROUND@#As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis.@*METHODS@#WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline; n = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC).@*RESULTS@#Acanthosis (98.46 ± 14.12 vs. 222.68 ± 71.10 μm, P < 0.01) and dermal cell infiltration (572.25 ± 47.45 vs. 762.47 ± 59.59 cells/field, P < 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83 ± 5112.09 vs. 4093.19 ± 2591.88 μm, P < 0.01) and scales (100,935.24 ± 41,167.77 vs. 41,604.41 ± 14,184.10 μm, P < 0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased.@*CONCLUSIONS@#IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.