Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer. Patients with TNBC have poor clinical outcome as they are non-responsive to current targeted therapies. There is an urgent need to identify new therapeutic targets and develop more effective treatment options for TNBC patients. Osthole, a natural product from C. monnieri, has been shown to inhibit certain cancer cells. However, the mechanisms of action as well as its effect on TNBC cells are not currently known. We investigated the effect of osthole in cultured TNBC cells as well as in a xenograft model of TNBC growth. We also used a high-throughput proteomics platform to identify the direct binding protein of osthole. We found that osthole inhibited the growth of a panel of TNBC cells and induced apoptosis in both cultured cells and TNBC xenografts. We used a high-throughput proteomics platform and identified signal transducer and activator of transcription 3 (STAT3) as a potential binding protein of osthole. We further show that osthole suppressed STAT3 in TNBC cells to inhibit growth and induce apoptosis. Overexpressing STAT3 in TNBC reduced the effectiveness of osthole treatment. These results provide support for osthole as a potential new therapeutic agent for the management of TNBC. Moreover, our results indicate that STAT3 may be targeted for the development of novel anti-TNBC drugs.

Keloid, a prevalent pathological skin lesion, presents significant challenges in terms of treatment efficacy. Photodynamic therapy (PDT), an increasingly popular adjuvant treatment, has shown significant potential in the management of various disorders, including cancer. However, the therapeutic potential of indocyanine green-mediated photodynamic therapy (ICG-PDT) for keloids has not yet been demonstrated. In this study, we divided the experimental groups into control group, Photothermal Therapy group, Photodynamic Therapy group, and Combined Therapy group. The in vitro investigation aimed to optimize the clinical application of PDT for keloid treatment by elucidating its underlying mechanism. Subsequently, on this basis, we endeavored to manage a clinical case of keloid by employing surgical intervention in conjunction with modified ICG-PDT. Our investigation revealed an unexpected outcome that ICG-PDT maximally inhibited the cellular activity and migration of keloid fibroblasts only when photodynamic mechanism took effect. Additionally, the induction of autophagy and apoptosis, as well as the inhibition of collagen synthesis, were particularly evident in this experimental group. Furthermore, the above therapeutic effect could be achieved at remarkably low drug concentrations. Building upon the aforementioned experimental findings, we successfully optimized the treatment modality for the latest case and obtained a more favorable treatment outcome. This study investigated the mechanism of ICG-PDT treatment and optimized the in vivo treatment regimen, demonstrating the significant therapeutic potential of ICG-PDT treatment in clinical keloid treatment.

ObjectiveTo evaluate the effectiveness and safety of deucravacitinib in Chinese patients with moderate-to-severe plaque psoriasis.MethodsThis retrospective study included 41 patients with moderate-to-severe plaque psoriasis treated with deu-cravacitinib 6 mg once daily for 16 weeks at the First Affiliated Hospital of Wenzhou Medical University between January and September 2024. Effectiveness was assessed by the psoriasis area and severity index (PASI), static physician’s global assessment (sPGA), palmoplantar psoriasis area and severity index (PPASI), modified nail psoriasis severity index (mNAPSI), and dermatology life quality index (DLQI) at baseline, week 4, week 8, week 12, and week 16. Adverse events were recorded during treatment. Laboratory parameters, including complete blood count, liver and kidney function, electrolytes, and lipids, were assessed at baseline, week 8, and week 16 to evaluate safety. Univariate and multivariate logistic regression analysis was performed to explore factors associated with achieving PASI75 at week 16, using baseline characteristics as independent variables.ResultsSignificant reductions from baseline in PASI and DLQI scores were observed from week 4 through week 16 (all P<0.01). Overall response rates for PASI75/90/100, sPGA 0/1, and DLQI 0/1 increased progressively over the treatment period. Response rates of PASI75/90/100 for the scalp, limbs, and trunk, PPASI75/90/100 for palmoplantar lesions, and mNAPSI75/90 for nail lesions increased progressively over time but with different trends. Scalp lesions improved most markedly from week 4, followed by the limbs, whereas improvements in trunk and palmoplantar lesions were relatively slower. Nail lesions responded more slowly, with only a minority of patients achieving marked improvement at week 16. Deucravacitinib demonstrated good tolerability and compatibility with concomitant medications. No severe adverse events were reported, indicating a favorable safety profile. Multivariate logistic regression analysis revealed no significant association between the achievement of PASI75 response at week 16 and patient age, body mass index (BMI), disease duration, or baseline PASI, sPGA, or DLQI scores (all P>0.05).ConclusionIn this real-world study of Chinese patients with moderate-to-severe plaque psoriasis, deucravacitinib demonstrated favorable effectiveness and safety over 16 weeks of treatment.