Corilagin relieves atherosclerosis via the toll-like receptor 4 signaling pathway in vascular smooth muscle cells.

INTRODUCTION: Corilagin possesses a diverse range of pharmacologic bioactivities. However, the specific protective effects and mechanisms of action of corilagin in the context of atherosclerosis remain unclear. In this study, we investigated the impact of corilagin on the toll-like receptor (TLR)4 signaling pathway in a mouse vascular smooth muscle cell line (MOVAS) stimulated by oxidized low-density lipoprotein (ox-LDL). Additionally, we examined the effects of corilagin in Sprague-Dawley rats experiencing atherosclerosis. METHODS: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining. RESULTS: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques. CONCLUSION: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.

Corilagin alleviates atherosclerosis by inhibiting NLRP3 inflammasome activation via the Olfr2 signaling pathway in vitro and in vivo.

Introduction: Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production. Methods: To investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE-/- mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein. Results: The vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway. Discussion: Our findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis.

Development and validation of a prognostic nomogram model in primary cutaneous and subcutaneous soft tissue angiosarcoma.

OBJECTIVE: The current study aimed to investigate the prognosis and treatment of primary cutaneous angiosarcoma (PCA) and primary subcutaneous angiosarcoma (PSCA), and tried to develop a prognostic nomogram model of them. METHODS: A total of 1763 cases retrieved from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Survival analyses were performed to explore the prognosis of patients and the effects of different treatment methods. All data were randomly allocated into a training set and a testing set to develop and validate the nomogram model. RESULTS: The findings showed that age, sex, grade, tumor size, multiple primary malignant tumors, stage, primary site surgery (PSS), radiotherapy (RT), and chemotherapy (CT) were correlated with prognosis (p < .05). The nomogram achieved good accuracy in predicting the prognosis. PSS + RT + CT showed the best prognosis for patients in stages I, II, and III (p < .05). CONCLUSION: PCA and PSCA are rare with poor prognoses. Patients undergoing PSS may not gain survival benefits from combining with RT or (and) CT, whereas PSS + RT + CT should be actively performed in earlier stages to improve the prognosis of patients. The nomogram model can be used to predict the overall survival rate and guide better treatment.

Clinical Characteristics-Assisted Risk Stratification for Extent of Thyroidectomy in Patients With 1-4 cm Solitary Intrathyroidal Differentiated Thyroid Cancer.

Background: Differentiated thyroid cancer (DTC) is the most common type of thyroid cancer. The 2015 American Thyroid Association (ATA) guidelines recommend that lobectomy is suitable for solitary intrathyroidal DTC (SI-DTC) of 1-4 cm. However, some SI-DTC patients with other high-risk characteristics still have poor prognosis and require more aggressive surgical methods. This study aimed to explore the clinical characteristics that are important for the identification and treatment of high-risk patients with SI-DTC of 1-4 cm. Methods: The study cohort was obtained from the SEER database, consisting of data between 2004 and 2013. The outcome measures were thyroid carcinoma-specific mortality (CSM) and all-cause mortality (ACM). Patient survival curves were examined using Kaplan-Meier analyses with log-rank tests and Cox proportional hazards regression analyses. Hazard ratios (HRs) were used to show the magnitude of the effect of disease stage on DTC-specific patient mortality. Results: The study included 55,947 patients with SI-DTC of 1-4 cm and 4,765 patients with DTC >4 cm. Tumor size, surgical approach, age, sex, race, and radiation exposure were independent risk factors for CSM and ACM. SI-DTC patients with female, age ≤45, and 1 cm< tumor size ≤2 cm were at low risk of CSM [HR = 0.014 (0.002-0.115)] and ACM [HR = 0.115 (0.077-0.171)] when stratified by age, sex, and tumor size. Compared to T3 patients, CSM was not significantly different in male patients, age >45, 2 cm< tumor size ≤3 cm [HR = 0.839 (0.414-1.700)] and male patients, age >45, 1 cm< tumor size ≤2 cm [HR = 0.751 (0.410-1.377)]. Furthermore, compared to T3 patients without extrathyroidal extension (ETE) and lymph node metastasis (LNM), more subgroups of SI-DTC of 1-4 cm had a similar prognosis. In addition, patients with SI-DTC of 1-4 cm showed similar rates of CSM and ACM to T3 patients without ETE, LNM, and distant metastasis (DM). Similar results were obtained when we set the age cut-off value as 55 years, according to the 8th edition of AJCC TNM system. Conclusions: Our study demonstrated that sex, age, and tumor size clearly differentiate SI-DTC of 1-4 cm into low-and high-risk categories. Survival rates were significantly lower in subgroups containing old males with larger tumors compared to younger females with small tumors. Total thyroidectomy may be favored in these high-risk subgroup patients.

Single Hormone Receptor-Positive Metaplastic Breast Cancer: Similar Outcome as Triple-Negative Subtype.

Background: Metaplastic breast cancer (MBC) is a rare and aggressive subtype of the breast. To understand the characteristics and prognosis of single hormone receptor-positive (HR+) MBC (estrogen receptor-positive [ER+]/progesterone receptor-negative [PR-] and ER-/PR+), we compared these tumors to double HR+ tumors as well as HR- tumors. Patients and Methods: The Surveillance, Epidemiology, and End Results database was used to analyze MBC between 1975 and 2016. The effect of HR status was evaluated using a multivariate Cox regression model. Results: We included 3369 patients with a median follow-up time of 42 months (range 0-322 months). In this study, 280 (8.3%) cases were double HR+ tumors, 2597 (77.1%) were double HR- tumors, and 492 (14.6%) cases were single HR+ tumors, of which 159 (4.7%) cases were ER-/PR+ tumors and 333 (9.9%) were ER+/PR- tumors. On multivariate Cox analysis, the prognosis was related to age, race/ethnicity, tumor grade, TNM stage, and surgery. HR status remained no impact on breast cancer-specific survival (BCSS). In the Kaplan-Meier curve, HR status was not associated with better BCSS or overall survival (OS). In patients without HER2 overexpression, the BCSS and OS of ER+/PR- and ER-/PR+ tumors were not significantly different from that of ER-/PR- and ER+/PR+ tumors. The difference remains no significant in patients with HER2 overexpression. Conclusions: In comparison with both ER-/PR- and ER+/PR+ tumors, we have identified clinically and biologically distinct features of single HR+ tumors. In patients with or without HER2 overexpression, the prognosis of single HR+ tumors was similar to ER-/PR- and ER+/PR+ tumors.