RESUMO
Purpose@#In this article, we aimed to investigate the influences of luteolin on inflammatory injury to cardiomyocytes induced by lipopolysaccharide (LPS). @*Materials and Methods@#H9c2 cells were pretreated with different concentrations of luteolin (10, 20, and 50 μM) for 12 h and then stimulated with 10 μg/mL LPS or no LPS for 6 h. Cell viability was detected by CCK-8 assay. Cell apoptosis was determined by flow cytometry. QRT-PCR and Western blotting were utilized to examine mRNA and protein levels. ELISA was used to determine the levels of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin (IL)-6, IL-1β, and IL-18 in cell supernatants among different groups of H9c2 cells. Immunofluorescence was applied to evaluate reactive oxygen species formation in H9c2 cells. M-mode images of echocardiography, the ejection fraction test, fractional shortening test, end-systolic volume test, and end-diastolic volume test of mouse heart function were obtained by ultrasonic electrocardiogram. @*Results@#Luteolin could alleviate inflammatory damage and inflammatory factor expression among LPS-induced H9c2 cells. Additionally, we found that luteolin decreased LPS-stimulated inflammatory damage in H9c2 cells by down-regulating NOD-like receptor family pyrin domain containing 3 (Nlrp3). Luteolin also improved myocardial function in mice treated with LPS and reduced myocardial relaxation. Luteolin reversed myocardial histological abnormalities in mice and reduced inflammation and cardiomyocyte apoptosis. Additionally, luteolin inhibited oxidative stress-mediated myocardial and systemic tissue damage in mice. Finally, luteolin reduced LPS-induced inflammatory damage in mouse cardiomyocytes by down-regulating Nlrp3. @*Conclusion@#We found that luteolin could reduce inflammatory damage to cardiomyocytes induced by LPS by down-regulating Nlrp3.
RESUMO
The objective of this study was to investigate the clinical pathological characteristics of breast cancer (BC) patients with secondary diabetes after systemic therapy without preexisting diabetes. A total of 1434 BC patients received systemic therapy and were analyzed retrospectively. Fasting plasma glucose (FPG) levels were monitored prior to the treatments, during the course of systemic therapy, and at the follow-up visits. Cox regression models were used to estimate the associations between the clinical pathological characteristics of BC and the cause-specific hazard of developing secondary diabetes. Among the 1434 BC patients, 151 had preexisting type 2 diabetes. Of the remaining 1283 patients with normal FPG levels prior to the systemic therapy, 59 developed secondary diabetes and 72 displayed secondary impaired fasting glucose (IFG) over a mean follow-up of 41 months. The prevalence of secondary type 2 diabetes in BC patients was 4.6 % (59/1283), which was obviously higher than that of the normal control group (1.4 %, P < 0.001). The percentage of older patients (P < 0.05), menopausal patients (P < 0.001), and obese patients (P < 0.01) tended to be lower in the secondary diabetic group. In addition, these patients with secondary diabetes had later pathological stages (P < 0.01), more lymph node metastasis (P < 0.05), negative estrogen receptor (ER) expression (P < 0.05), and smaller size of tumors (P < 0.05). After adjusting for age and BMI, the risk of developing secondary diabetes and IFG in subjects with later pathological stage BC (hazard ratio (HR) = 1.623; 95 % confidence interval (CI) 1.128-2.335 (P < 0.01)), negative progesterone receptor (PR) expression (HR = 0.530; 95 % CI 0.372-0.755 (P < 0.001)), positive human epidermal growth factor receptor 2 (HER2) expression (HR = 1.822; 95 % CI 1.230-2.700 (P < 0.01)), and more lymph node metastasis (HR = 1.595; 95 % CI 1.128-2.258 (P < 0.01)) was significantly higher. In conclusion, this study shows that an increase in the incidence of diabetes among breast cancer survivors after systemic therapy, especially the patients with later pathological stages, more lymph node metastasis, negative hormone receptor expression, and positive HER2 expression. Our study suggests that greater diabetes screening and prevention strategies among breast cancer patients after systemic treatment are needed in China.
