RESUMEN

Malassezia, the most abundant fungal commensal on the mammalian skin, has been linked to several inflammatory skin diseases such as atopic dermatitis, seborrheic dermatitis and psoriasis. This study reveals that epicutaneous application with Malassezia globosa (M. globosa) triggers skin inflammation in mice. RNA-sequencing of the resulting mouse lesions indicates activation of Interleukin-17 (IL-17) signaling and T helper 17 (Th17) cells differentiation pathways by M. globosa. Furthermore, our findings demonstrate a significant upregulation of IL-23, IL-23R, IL-17A, and IL-22 expressions, along with an increase in the proportion of Th17 and pathogenic Th17 cells in mouse skin exposed to M. globosa. In vitro experiments illustrate that M. globosa prompts human primary keratinocytes to secrete IL-23 via TLR2/MyD88/NF-κB signaling. This IL-23 secretion by keratinocytes is shown to be adequate for inducing the differentiation of pathogenic Th17 cells in the skin. Overall, these results underscore the significant role of Malassezia in exacerbating skin inflammation by stimulating IL-23 secretion by keratinocytes and promoting the differentiation of pathogenic Th17 cells.

Asunto(s)

Diferenciación Celular , Interleucina-23 , Queratinocitos , Malassezia , Células Th17 , Malassezia/inmunología , Queratinocitos/microbiología , Queratinocitos/inmunología , Queratinocitos/metabolismo , Células Th17/inmunología , Animales , Interleucina-23/metabolismo , Humanos , Ratones , Transducción de Señal , FN-kappa B/metabolismo , Receptor Toll-Like 2/metabolismo , Interleucina-17/metabolismo , Piel/microbiología , Piel/patología , Piel/inmunología , Modelos Animales de Enfermedad , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Células Cultivadas , Ratones Endogámicos C57BL , Interleucina-22

RESUMEN

Benvitimod has been successfully used in the treatment of psoriasis and atopic dermatitis (AD). However, the mechanism remains to be clarified. We aim to assess the effects of benvitimod on MC903-induced dermatitis in mice and to investigate the effects of benvitimod on filaggrin (FLG), involucrin (IVL), and loricrin (LOR) expressions and possible mechanism. MC903-induced mouse AD model was used to evaluate the effects of benvitimod. Filaggrin, involucrin, and loricrin protein and mRNA expressions in lesions of mice dermatitis were measured by Western blot and quantitative real-time PCR. In vitro, normal human epidermal keratinocytes (NHEKs) were cultured and benvitimod was used to treat NHEKs primed with IL-4 and IL-13. Then AHR and OVOL1 in NHEKs were knocked down to evaluate the role of AHR and OVOL1 in the effects of benvitimod. Topical treatment of benvitimod repaired skin barrier and alleviated skin inflammation in mouse AD model. This effect was inhibited by pretreatment with an AHR antagonist. Benvitimod upregulated the filaggrin, involucrin, and loricrin expressions in lesions of mouse AD model. In addition, benvitimod upregulated the filaggrin, involucrin, and loricrin expressions in NHEKs. Knockdown of AHR or OVO-like (OVOL)1 abrogated the upregulation of filaggrin, involucrin, and loricrin induced by benvitimod. Benvitimod attenuated MC903-induced mouse dermatitis and upregulated filaggrin, involucrin, and loricrin expressions via AHR-OVOL1 axis.

Asunto(s)

Dermatitis Atópica , Modelos Animales de Enfermedad , Proteínas Filagrina , Proteínas de Filamentos Intermediarios , Queratinocitos , Precursores de Proteínas , Receptores de Hidrocarburo de Aril , Regulación hacia Arriba , Proteínas Filagrina/metabolismo , Animales , Precursores de Proteínas/metabolismo , Precursores de Proteínas/genética , Ratones , Humanos , Queratinocitos/metabolismo , Queratinocitos/efectos de los fármacos , Proteínas de Filamentos Intermediarios/metabolismo , Proteínas de Filamentos Intermediarios/genética , Dermatitis Atópica/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Regulación hacia Arriba/efectos de los fármacos , Receptores de Hidrocarburo de Aril/metabolismo , Receptores de Hidrocarburo de Aril/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Células Cultivadas , Piel/patología , Piel/metabolismo , Piel/efectos de los fármacos , Ratones Endogámicos BALB C , Transducción de Señal/efectos de los fármacos , Proteínas de Unión al ADN , Factores de Transcripción

Asunto(s)

Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/genética , Melanoma/terapia , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/terapia , Metilación , Pronóstico , Inmunoterapia , ARN , Biomarcadores de Tumor , Melanoma Cutáneo Maligno

RESUMEN

Natural medicine has been widely used for clinical treatment and health care in many countries and regions. Additionally, extracting active ingredients from traditional Chinese medicine and other natural plants, defining their chemical structure and pharmacological effects, and screening potential druggable candidates are also uprising directions in new drug research and development. Physiologically based pharmacokinetic (PBPK) modeling is a mathematical modeling technique that simulates the absorption, distribution, metabolism, and elimination of drugs in various tissues and organs in vivo based on physiological and anatomical characteristics and physicochemical properties. PBPK modeling in drug research and development has gradually been recognized by regulatory authorities in recent years, including the U.S. Food and Drug Administration. This review summarizes the general situation and shortcomings of the current research on the pharmacokinetics of natural medicine and introduces the concept and the advantages of the PBPK model in the study of pharmacokinetics of natural medicine. Finally, the pharmacokinetic studies of natural medicine using the PBPK models are summed up, followed by discussions on the applications of PBPK modeling to the enzyme-mediated pharmacokinetic changes, special populations, new drug research and development, and new indication adding for natural medicine. This paper aims to provide a novel strategy for the preclinical research and clinical use of natural medicine.

Asunto(s)

Medicina , Preparaciones Farmacéuticas/química , Modelos Biológicos , Farmacocinética

RESUMEN

Trichilemmal carcinoma (TC) is a rare malignant cutaneous adnexal neoplasm originating from the outer root sheath of hair follicles, which occurs commonly in sun-exposed areas of the elderly. Here, we introduce a case of a 24-year-old woman with TC on her scalp.

RESUMEN

Mucormycosis is an opportunistic fungal infection driven by subphylum Mucormycotina. Cutaneous mucormycosis is the third most common presentation of mucormycosis, and its characterized presentation is an indurated plaque that rapidly evolves to necrosis. Trichophyton rubrum is one of the most common dermatophytes that mainly cause superficial infections and seldom induce deep infections. The present report presents a case of cutaneous fungal infection, in which two kinds of fungus were isolated, and the skin lesion mimicked pyoderma gangrenosum. Trichophyton rubrum was isolated from the crust and hyphae of subphylum Mucormycotina were found in dermal tissue. The irregular systemic and topical use of steroid therapy is the possible cause of the mixed fungal infection in this patient, suggesting the importance of regular steroid therapy.