Interleukin 23 (IL-23) belongs to interleukin 6 super-family [1]. IL-12/23 p40 is the common subunit for them, which is covalently linked to either a p19 subunit to form IL-23 or a p35 subunit to form IL-12 [2]. Both cytokines are mainly expressed by activating dendrite cells or macrophages under the stimulation of pathogens. IL-23 was also reported to be secreted by tumor associated macrophages in tumor microenvironment [3]. Interestingly, IL-23 spur different immune pathways [4]. IL-12 induces IFN-γ-producing Th1 cell development and enhances cytotoxic, anti-microbial and anti-tumor responses; whereas IL-23 expands Th17 cells, which is mainly involved in the pathology of autoimmunity and chronic inflammatory disease [5]. Although the role of Th17 in tumor progression remains controversial, the role of IL-23 in tumor incidence and metastasis was established in the mouse model. For example, mice lacking IL-23p19 were resistant to DMBA/TPA-induced skin papilloma [6-7]. Recently, IL-23 was also reported to promote carcinogenesis and metastasis in the 3′-methylcholanthrene induced fibrosarcoma through suppressing the innate immune response [8]. However, the role of IL-23 in metastatic prostate cancer is unclear. In this study, we found that IL-23 was highly expressed in metastatic prostate cancer cells. We further proved that IL-23 could directly promote prostate cancer metastasis via a STAT3/ROR gamma signal, so we further explored the relationship between IL-23 and STAT3/ROR gamma in prostate metastasis. We found that IL-23 and STAT3/ROR gamma were highly correlated in metastatic prostate cancer cell lines directed. STAT3 belongs to the signal transducer and activator of transcription (STAT) family of signal responsive transcription factors, which consists of seven members encoded by distinct genes. In non-stimulated cells, STAT3, like other STATs proteins, are kept in an inactive

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BackgroundThe importance of doxorubicin (Dox), as a potent antitumor antibiotic, is limited by the development of life-threatening cardiomyopathy. It has been shown that free radicals are involved in acute doxorubicin-induced toxicity. The aim of this study was to determine the protective effect of vitamin E and telmisartan in acute doxorubicin induced cardiotoxicity.MethodsThirty two male Sprague - Dawly rats were involved in this study and were randomly separated into 4 groups, eight rats in each group, one group received normal saline I.P as control and second group received doxorubicin 20 mg/kg I.P, the other two groups also received doxorubicin 20 mg/kg I.P as single dose after seven cumulative doses (for seven days) of vitamin E (100 mg/kg) and telmisartan (1 mg/kg) respectively. Immunofluorescent staining for monocytes infiltration and analyses of plasma by (ELISAs) for MCP-1and troponin I. Western immunoblotting assay for ICAM-1, while left ventricular function was analyzed by microcatheter, also estimated the level of oxidative stress parameters (MDA and Catalase) and cardiac enzymes activities (CK-MB and LDH) before starting drugs treatment and after treatment period by 48 hours.ResultsThe immunofluorescent staining showed that administration of vitamin E and telmisartan are attenuated of mononuclear cell infiltration; (p < 0.05 vs. Dox group), also reduced the level of chemokines MCP-1 and ICAM-1 expression compared with Dox group only, and there is marked reduction of myocardial troponin-I levels with improved LV function in vitamin E and telmisartan treated group. Doxorubicin treatment increased MDA, LDH, CK-MB levels significantly (P < 0.01), and were counteracted by administration of vitamin E and telmisartan, but did not significantly affect serum catalase activity.ConclusionsAntioxidant effect (Vitamin E and telmisartan) have been shown to decrease doxorubicininduced cardiotoxicity.

IntroductionEndotoxemia and the systemic inflammatory response syndrome have a significant impact on post-surgery outcome, particularly in the elderly. The cytokine response to endotoxin is altered by aging. We tested the hypothesis that vulnerability to endotoxemic cardiac depression increases with aging due to age-related augmentation of myocardial inflammatory responses.MethodsAdult (4 to 6 months) and old (20 to 22 months) C57/BL6 mice were treated with endotoxin (0.5 mg/kg, iv). Left ventricle (LV) function was assessed using a microcatheter system. Chemokines and cytokines in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells in the myocardium were examined using immunofluorescence staining.ResultsOld mice displayed worse LV function (cardiac output: 3.0 ± 0.2 mL/min versus 4.4 ± 0.3 mL/min in adult mice) following endotoxin treatment. The exaggerated cardiac depression in old mice was associated with higher levels of monocyte chemoattractant protein-1 (MCP-1) and keratinocyte chemoattractant (KC) in plasma and myocardium, greater myocardial accumulation of mononuclear cells, and greater levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) in plasma and myocardium. Neutralization of MCP-1 resulted in greater reductions in myocardial mononuclear cell accumulation and cytokine production, and greater improvement in LV function in old mice while neutralization of KC had a minimal effect on LV function.ConclusionOld mice have enhanced inflammatory responses to endotoxemia that lead to exaggerated cardiac functional depression. MCP-1 promotes myocardial mononuclear cell accumulation and cardiodepressant cytokines production, and plays an important role in the endotoxemic cardiomyopathy in old mice. The findings suggest that special attention is needed to protect the heart in the elderly with endotoxemia.

The present data proved the over-expression of Notch1/JAGD1 and its association with tumor progression in human cervical cancer, which might be a potential valuable biomarker for cervical cancer and further studies need.