Object To study the protective effect of crocetin on myocardial ischemia induced by isoproterenol (ISO). Methods Myocardial ischemia was induced by subcutaneous injection of ISO (30 mg/kg for two days, once a day). The experimental animals were randomly divided into the normal group, ISO group, positive control group and three crocetin groups (25, 50, 100 mg/kg). Cardiac indexes were examined. The level of LDH, CK, MDA in serum were measured. The content of MDA, GSH-Px and the ATPase activity heart and mitochondria were assayed by colorimetric analysis. The histopathological change of myocardia was investigated by HE staining. Results Compared with the model group, crocetin can significantly reduce the cardiac indexes, obviously decrease the level of MDA, LDH and CK in the serum. Crocetin can significantly increase the activities of Na +, K +-ATPase; Ca 2+ , Mg 2+ -APTase; GSH-Px. The histopathological changes confirmed the protective effects of crocetin on the myocardial injury. Conclusion Crocetin could alleviate the acute myocardial ischemia induced by ISO in rats.

At present,pancreatic ductal adenocarcinama (PDAC) is one of the deadliest malignant solid tumors,with poor prognosis and 5-year survival rate of 5％.Although understanding of the pathogenesis has greatly been improved for nearly two decades,there isn't a breakthrough in clinical therapy of the PDAC,and finding a new and effective therapy is badly needed.Genetic analysis showed that KRAS was one of the earliest and great probability mutated gene in the PDAC,played a significant role in initiation,progression,and metastasis of cancer,and predicted to being a good target of anti-PDAC.But a KRAS-targeted effective drug is lacking in clinic.The direct KRAS-targeted therapy will bright prospects.Meanwhile,locking localization and activity of cell membrane through post-translational modifications to KRAS combined with inhibiting KRAS downstream pathway is a good way of the KRAS-targeted PDAC therapy.

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.