ABSTRACT
Hexabromocyclododecane (HBCD) is a persistent organic pollutant (POP). HBCD is found in the blood and tissues of most populations and causes a range of toxicological damage to tissues and cells. However, the toxicological effects of HBCD on chondrocytes are not fully understood. Here, we evaluated the toxicological effects of HBCD on chondrocytes and cartilaginous tissue. For this, a model of primary cartilage cells was established. Chondrocytes were exposed to different concentrations of HBCD. Western blot, indirect immunofluorescence, ELISA and other biochemical experiments were performed to analyze the toxicological effects of HBCD on chondrocytes/articular cartilage tissue. Cell proliferation assays showed that HBCD caused a reduction in the proliferative capacity of chondrocytes, and further work indicated that HBCD induces chondrocyte death. Further experiments demonstrated that HBCD caused an inflammatory response in chondrocytes by evaluating the levels of inflammatory factors. We found that HBCD led to PANoptosis in chondrocytes by detecting panapoptosis-related marker molecules, and experimental data indicated that apoptosis markers (cleaved caspase-3/7), pyroptosis markers (caspase-1/GSDMD-N) and necroptosis markers (pMLKL/RIPK3) were upregulated after HBCD treatment. Subsequent experiments illustrated that HBCD activated the DAMP sensor NLRP3, which then mediated ZBP1-induced PANoptosis. In the in vivo model, the experimental animals were administered HBCD at 25, 50 and 100 µg/kg/week for 15 weeks. We found that HBCD led to an inflammatory response in articular cartilage tissue. The safranin O-fast green assay showed a certain degree of damage to cartilage tissue under HBCD treatment. Furthermore, HBCD resulted in an increase in MMP13 expression and a downregulation of COL2 expression in chondrocytes/cartilaginous tissues. HBCD decreased the exercise ability of mice in vivo. These data indicate that HBCD leads to chondrocyte damage. In summary, this study lays the foundation for further exploration of the toxicological effects of HBCD on bone and joints.
Subject(s)
Cartilage, Articular , Chondrocytes , Mice , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolismABSTRACT
Objective:To investigate the value of ultrasound in evaluating pathologically complete response(pCR) of neoadjuvant chemotherapy(NAC) for breast cancer.Methods:A retrospective analysis was performed in 67 breast cancer patients who received NAC in the Second Affiliated Hospital of Harbin Medical University from January 2018 to December 2019. Ultrasound examination was performed before and after NAC, and two-dimensional, color and elastic images were stored for subsequent analysis. According to the operation pathological results after NAC, the patients were divided into two groups, pCR group and npCR group, using the Miller-Payne criteria as the evaluation criteria. Chi-square test was used to compare the ultrasound characteristics of breast masses in pCR group and npCR group before NAC. The accuracy, sensitivity, specificity, positive predicative value(PPV) and negative predicative value(NPV) of pCR were analyzed using ROC curve. The difference of pCR estimated by ultrasound in different molecular types was also analyzed.Results:①Of the 67 patients, 16 achieved pCR and 51 achieved npCR. Among the 16 pCR patients, 11(68.8%) were evaluated correctly and 5(31.2%) were wrong.Among the 51 npCR patients, 49(96.1%) were evaluated correctly and 2(3.9%) were wrong. ②There was no statistically significant difference between pCR and npCR in ultrasound features of pre-NAC breast masses( P>0.05). ③After the whole process of NAC, the accuracy, sensitivity, specificity, PPV and NPV were 89.6%, 68.8%, 96.1%, 84.6%, and 90.7%, respectively; The area under ROC curve was 0.824. ④The diagnostic efficiency of pCR estimated by ultrasound was higher for Luminal B and HER-2 breast cancer. Conclusions:The accuracy of pCR after NAC evaluated by ultrasound is 89.6%, with different diagnostic efficiency in different molecular types.
ABSTRACT
Objective To investigate the chemical constituents of marine sponge Mycale sp.collected from the South China Sea.Methods The ethyl acetate extract of the marine sponge Mycale sp.was separated and purified by repeated column chromatography on silica gel, Sephadex LH-20 and reversed-phase high-performance liquid chromatography (RP-HPLC).The structures of these compounds were identified by means of various modern spectroscopic techniques and comparison with their physicochemical properties to reported data.The tumor cell growth inhibitory activities of these compounds against human breast cancer cell lines MCF-7 and human lung cancer cell lines PC9 were tested by Cell Counting Kit-8 (CCK-8) method.Results Ten compounds were isolated and identified as cyclo-(Pro-Ile)(1),cyclo-(Pro-Leu)(2),cyclo-(Ile-Leu)(3),cyclo-(Phe-Pro)(4),cyclo-(Phe-Val)(5),cyclo-(Phe-Leu)(6),cyclo-(Phe-Ile)(7), 2′-deoxythymidine (8), thymine (9), 5-hydroxy-3,4-dimethyl-5-pentyl-2(5H)-furanone (10).These compounds showed weak tumor cell growth inhibitory activities toward cells MCF-7 and PC9 in vitro.Conclusion Compounds 1, 2, 4, 5, 6, 7 and 10 were isolated from the sponge Mycale sp.for the first time.It is the first time to report the antitumor activity evaluation for compounds 1~10.
