Evidence on the therapeutic role of thiolutin in imiquimod-induced psoriasis-like skin inflammation in mice.

INTRODUCTION: A recent study confirmed that thiolutin (THL), as a potent inflammasome inhibitor, plays a promising therapeutic role in multiple inflammatory disease models. However, the effect of THL on psoriasis has not been reported so far. METHODS: A psoriasiform dermatitis model was prepared by applying 5% imiquimod (IMQ) cream on mice. A total of 36 mice were randomly divided into six groups: control, model, model + THL-L/M/H (THL, 1/2.5/5 mg/kg/day), model + methotrexate (1 mg/kg/day). Psoriasis area and severity index (PASI) scores were observed and calculated. The histological changes in skin, liver, and kidney tissues were observed by hematoxylin and eosin staining. Alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and blood creatinine were measured by automatic biochemistry analyzer. The size of the spleens was determined, and the proportion of Foxp3 + CD4+ regulatory T (Treg) cells in the spleens was tested by flow cytometry. The proinflammatory factors and nucleotide oligomerization domain nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome protein levels were examined by reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry, respectively. RESULTS: THL administration preeminently reduced the thickness, scaling, and erythema of the skin lesions, alleviated IMQ-induced psoriasiform lesions in mice, reduced the PASI score, and ameliorated histopathological changes in mouse skin. The spleen index was decreased by almost half and the proportion of Foxp3 + CD4+ Treg cells was increased after intervention by THL. THL intervention did not affect liver and kidney function, but decreased the expression levels of proinflammatory factors and NLRP3 inflammasome in the skin of psoriatic mice. CONCLUSIONS: THL may alleviate IMQ-induced psoriasis-like manifestations in mice by inhibiting NLRP3 inflammasome.

Chemotherapy-induced oral mucositis induced by low dose methotrexate: a case report and literature review / 口腔疾病防治

Objective@# To investigate the diagnosis and treatment for oral mucositis induced by low-dose methotrexate and to provide a reference for clinicians@*Methods @# A case of severe chemotherapy-induced oral mucositis caused by short-term use of low-dose methotrexate (the maximum cumulative dose within 1 week) was reported and reviewed in combination with the literature.@*Results@# The patient was treated with low-dose methotrexate (2.5 mg orally every other day at weeks 1, 2, and 4; the third week, 2.5 mg each time for 3 consecutive days for twice, with a maximum cumulativedose of 15 mg within a week). After irregular medication for approximately three weeks, the patient gradually developed severe erosion of the lips, pain, difficulty eating, and skin erosion on both legs. Methotrexate was stopped after admission, and local symptomatic treatments such as Kangfuxin solution were given. Recombinant human granulocyte colony-stimulating factor was used systemically when combined with neutropenia. After treatment, the chemotherapy-induced oral mucositis and skin lesions were improved. A literature review shows that chemotherapy-induced oral mucositis is a toxic reaction to high-dose methotrexate, while cases of severe chemotherapy-induced oral mucositis caused by low-dose methotrexate are rare. Studies have found that the more risk factors patients have, such as poor local oral conditions and systemic diseases such as liver and kidney dysfunction and diabetes, the higher the risk of chemotherapy-induced oral mucositis. Clinicians should cooperate with dentists to address oral diseases as much as possible before using chemotherapy drugs. In addition, when ordering patients to take methotrexate, we should pay attention to the patient's general condition and susceptibility factors, standardize the frequency and dose of administration, adopt personalized treatment plans, and give patients detailed medication education to prevent the occurrence of adverse consequences caused by medication errors. If methotrexate poisoning occurs, the drug should be stopped in time, detoxification and active symptomatic and supportive treatment should be given. Basic oral care, cryotherapy, laser therapy, nutritional support and analgesic drugs are common treatments for chemotherapy-induced oral mucositis. Systemic administration of granulocyte colony-stimulating factor may be considered when accompanied by neutropenia.@*Conclusion@# It is necessary to be alert to the occurrence of severe chemotherapy-induced oral mucositis caused by low-dose methotrexate in clinical practice.