RESUMEN
Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer that has been on the rise in recent times, particularly among older individuals. Cornulin (CRNN) is increasingly recognized as an oncogene involved in developing various types of tumors. However, the precise contribution to cSCC remains unclear. Our study observed a significant increase in CRNN expression in cSCC samples compared to healthy skin. CRNN expression in the SCL-1 cell line derived from cSCC was reduced, leading to a halt in cell growth during the transition from the G1 phase to the S phase. This reduction inhibits cell division, promotes cell death, and decreases cell invasion and migration. CRNN overexpression has been found to enhance cell growth and prevent cells from undergoing natural cell death, and the cancer-promoting effects of CRNN are linked to AKT activation. Using a mouse xenograft model, we demonstrated that the inhibition of CRNN led to a decline in cSCC tumor growth in a living organism, providing evidence of CRNN's involvement in cSCC occurrence and development. This study establishes a foundation for evaluating the effectiveness of CRNN in treating cSCC, enabling further investigation in this area.
Asunto(s)
Carcinoma de Células Escamosas , Proliferación Celular , Proteínas Proto-Oncogénicas c-akt , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Animales , Línea Celular Tumoral , Ratones , Progresión de la Enfermedad , Movimiento Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones Desnudos , Invasividad NeoplásicaRESUMEN
Background: Both traditional Chinese medicine (TCM) and Western medicine are widely applied in the treatment of eczema, but there are few reports on integrated TCM and Western medicine for eczema. Objective: This meta-analysis carried out the evaluation on the efficacy of integrated TCM and Western medicine in the treatment of eczema. Methods: PubMed, Web of Science, Embase, CNKI, and Wanfang databases were searched for all possible randomized controlled trials from 2000 to 2021. A meta-analysis of the included studies was also performed using Stata16 software. Results: A total of 16 studies including 1946 patients were included. Compared with the control group, the pooled results of the 16 studies showed that effective rate in the treatment group was higher (OR = 4.50, 95% CI: 3.16-6.40, P < 0.05), and the pooled data of 15 studies revealed that the cure rate was increased in the treatment group (OR = 2.60, 95% CI: 2.13-3.18, P < 0.05). Additionally, compared with the control group, pooled data of 11 studies demonstrated that lesion area after treatment was reduced in the treatment group (SMD = -1.91; 95% CI: -2.51, -1.31; P < 0.05), and pooled data of 9 studies showed that the degree of pruritus after treatment in the treatment group was lower (SMD = -1.69; 95% CI: -2.07, -1.30; P < 0.05). Conclusion: In comparison with Western medicine alone, integrated TCM and Western medicine are a more effective treatment for eczema, which can not only significantly improve the effective rate and cure rate but also reduce the lesion area and degree of pruritus.
Asunto(s)
Medicamentos Herbarios Chinos , Eccema , China , Medicamentos Herbarios Chinos/uso terapéutico , Eccema/tratamiento farmacológico , Humanos , Medicina Tradicional China , Prurito/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Licochalcone A (Lico A) is a natural flavonoid belonging to the class of substituted chalcone that has various biological effects. Mast cells (MCs) are innate immune cells that mediate hypersensitivity and pseudo-allergic reactions. MAS-related GPR family member X2 (MRGPRX2) on MCs has been recognized as the main receptor for pseudo-allergic reactions. In this study, we investigated the anti-pseudo-allergy effect of Lico A and its underlying mechanism. Substance P (SP), as an MC activator, was used to establish an in vitro and in vivo model of pseudo-allergy. The in vivo effect of Lico A was investigated using passive cutaneous anaphylaxis (PCA) and active systemic allergy, along with degranulation, Ca2+ influx in vitro. SP-induced laboratory of allergic disease 2 (LAD2) cell mRNA expression was explored using RNA-seq, and Lico A inhibited LAD2 cell activation by reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence staining. Lico A showed an inhibitory effect on SP-induced MC activation and pseudo-allergy both in vitro and in vivo. The nuclear factor (NF)-κB pathway is involved in MRGPRX2 induced MC activation, which is inhibited by Lico A. In conclusion, Lico A inhibited the pseudo-allergic reaction mediated by MRGPRX2 by blocking NF-κB nuclear migration.
Asunto(s)
Chalconas , Hipersensibilidad , Degranulación de la Célula , Chalconas/farmacología , Humanos , Hipersensibilidad/tratamiento farmacológico , Mastocitos , FN-kappa B , Proteínas del Tejido Nervioso , Receptores Acoplados a Proteínas G/genética , Receptores de NeuropéptidoRESUMEN
Imidazolidinyl urea (IU) is used as an antimicrobial preservative in cosmetic and pharmaceutical products. IU induces allergic contact dermatitis, however, the mechanism has not yet been elucidated. Mas-related G protein-coupled receptor-X2 (MRGPRX2) triggers drug-induced pseudo-allergic reactions. The aims of this study were to determine whether IU activated mast cells through MRGPRX2 to further trigger contact dermatitis. Wild-type (WT) and KitW-sh/HNihrJaeBsmJNju (MUT) mice were treated with IU to observe its effects on local inflammation and mast cells degranulation in vivo. Laboratory of allergic disease 2 cells were used to detect calcium mobilization and release of inflammatory mediators in vitro. WT mice showed a severe local inflammatory response and contact dermatitis, whereas only slight inflammatory infiltration was observed in MUT mice. Thus, MRGPRX2 mediated the IU-induced activation of mast cells. However, histamine, a typical allergen, was not involved in this process. Tryptase expressed by mast cells was the major non-histaminergic inflammatory mediator of contact dermatitis. IU induced anaphylactic reaction via MRGPRX2 and further triggering non-histaminergic contact dermatitis, which explained why antihistamines are clinically ineffective against some chronic dermatitis.
RESUMEN
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Several previous studies have shown that fibulin-3 participates in the occurrence and development of various tumors; however, its role in cSCC remains unknown. In the present study, we observed that the expression of fibulin-3 was downregulated in cSCC tissues compared with normal skin tissues, which was due to fibulin-3 promoter methylation. In vitro, knockdown of fibulin-3 in cSCC cell lines A431 and SCL-1 cells promoted cell proliferation, protected cells against apoptosis and enhanced migration and invasion abilities. Conversely, overexpression of fibulin-3 inhibited cell proliferation by promoting growth arrest during the G1/S phase transition, induced apoptosis, and reduced migration and invasion abilities. These anticarcinogenic effects of fibulin-3 were associated with inhibition of the AKT signaling pathway. Through a mouse xenograft model, we found that fibulin-3 overexpression inhibited the cSCC tumor growth in vivo. Our results suggest that fibulin-3 has anti-tumorigenic activities in cSCC. Downregulation of fibulin-3 is involved in cSCC development and it may serve as a novel therapeutic target of this disease.
Asunto(s)
Carcinogénesis/genética , Carcinoma de Células Escamosas/genética , Proteínas de la Matriz Extracelular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Carcinogénesis/patología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Metilación de ADN , Regulación hacia Abajo , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Piel/patología , Neoplasias Cutáneas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and infiltration of inflammatory cells. CRNN is a major component of the cornified cell envelope and implicated in several epithelial malignancies. Here, we show that CRNN expression was increased in the lesioned epidermis from the patients with psoriasis vulgaris and skin lesions from the imiquimod (IMQ)-treated mice. Expression of CRNN in cultured keratinocytes (HEKa and HaCaT) was also induced by M5, a mixture of five pro-inflammatory cytokines (i.e., IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α). Lentiviral expression of CRNN increased cell proliferation by inducing cyclin D1. Conversely, knockdown of CRNN by small interfering RNA suppressed G1/S transition and attenuated the M5-induced proliferation. In addition, CRNN overexpression increased the phosphorylation and activation of phosphoinositide 3-kinase and Akt. Inactivation of the phosphoinositide 3-kinase and Akt pathways using small interfering RNA or selective inhibitors (LY294002 and MK2206) reduced the proliferative effects of CRNN. Furthermore, topical use of anti-psoriatic calcipotriol effectively decreased expression of CRNN, inhibited the Akt activation and improved the IMQ-stimulated psoriasis-like pathologies. Taken together, these results suggest that induced expression of CRNN may contribute to the pathogenesis of psoriasis.
Asunto(s)
Regulación de la Expresión Génica , Proteínas de la Membrana/genética , Proteínas de Neoplasias/genética , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Psoriasis/genética , ARN/genética , Piel/fisiopatología , Animales , Western Blotting , Proliferación Celular , Células Cultivadas , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Imiquimod/toxicidad , Queratinocitos/metabolismo , Queratinocitos/patología , Proteínas de la Membrana/biosíntesis , Ratones , Ratones Endogámicos BALB C , Proteínas de Neoplasias/biosíntesis , Psoriasis/metabolismo , Psoriasis/patología , Transducción de Señal , Piel/metabolismoRESUMEN
Shikonin, which is a major ingredient of the traditional Chinese herb Lithospermum erythrorhizon, possesses various biological functions, including antimicrobial, anti-inflammatory, and antitumor activities. The present study aimed to determine the molecular mechanisms underlying the effects of shikonin on HaCaT cell apoptosis. Treatment with shikonin significantly inhibited the viability of HaCaT cells in a dose and timedependent manner, and promoted cell cycle arrest at G0/G1 phase and apoptosis. In addition, shikonin treatment reduced the mitochondrial membrane potential and induced reactive oxygen species generation. The results of a western blot analysis demonstrated that shikonin significantly activated caspase 3 expression, downregulated Bcell lymphoma 2 (Bcl2) expression, and upregulated Bcl2associated X protein and Bcl2 homologous antagonist killer expression in a dosedependent manner in HaCaT cells. Furthermore, shikonin decreased extracellular signalregulated kinase (Erk) and Akt phosphorylation. These results indicated that shikonin may exert its antiproliferative effects by inducing apoptosis via activation of the mitochondrial signaling pathway and inactivation of the Akt and Erk pathways in HaCaT cells. Therefore, the present study suggested that shikonin may have potential as a component of therapeutic strategies for the treatment of skin diseases.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Apoptosis/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Naftoquinonas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Caspasas/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as agranular cluster of differentiation (CD)4+/CD56+ hematodermic neoplasm, is a rare and aggressive type of lymphoma, with only ~100 cases reported worldwide. BPDCN is a hematological malignancy derived from precursors of plasmacytoid dendritic cells and is clinically characterized by cutaneous manifestations involving the lymph nodes and peripheral blood, a leukemia-like dissemination and a poor prognosis. The present study reports the case of a 54-year-old male who presented with symptoms characteristic of BPDCN. Pathological and immunohistochemical analysis of abdominal skin lesion biopsies were used to determine a diagnosis of stage IIIE BPDCN. Although cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy was administered, the patient succumbed to BPDCN nine days after the discontinuation of chemotherapy. Thus, the period from BPDCN presentation to mortality was ≤3 months. The case reported in the present study was characterized by rapid development and poor prognosis, and displayed additional features of BPDCN, including systemic dissemination and a short survival period.
RESUMEN
Eccrine spiradenoma (ES) is a rare, benign adnexal neoplasm that may easily be mistaken for glomus lesions or angioleiomyoma due to its painfulness and florid vascularization. A 44-year-old male with a blue-colored, nodular tumor on the left knee, present for 10 years, was submitted for diagnosis. Dermatological examination was undertaken, followed by surgical excision of the subcutaneous lesion and histopathological examination of the tissue. Subjective symptoms included tenderness upon palpation and routine investigations were within normal limits. Immunohistochemical analysis of the tumor cells demonstrated positive staining for CK5/CK6, CK8/CK18, S100, as well as small vacuole-like positive for EMA, and was therefore diagnosed as ES. The results of the present study suggest that immunohistochemical assays may be helpful to clarify the diagnosis and differentiate ES from other painful subcutaneous tumors exhibiting similar clinical and histological presentations.