Morphine enhances renal cell carcinoma aggressiveness through promotes survivin level.

BACKGROUND: Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. Unfortunately, the results obtained by these studies are still contradictory. METHODS: In this study, we investigated the effect of morphine in human clear cell renal cell carcinoma 786-O, RLC-310 cells and whether morphine affects on tumor growth in human clear cell renal cell carcinoma 786-O, RLC-310 cells. The cell proliferation was determined by MTT assay, cell proliferation, migration and invasion assays. Immunofluorescence staining and Q-PCR was used to determine the Survivin expression. RESULTS: It was shown that morphine enhances proliferation of 786-O, RLC-310 cells, whereas morphine promoted the growth and aggressive phenotype of 786-O and RLC-310 cells in vitro though Survivin-dependent signaling. CONCLUSIONS: Our data showed that morphine promotes RCC growth and increases RCC progression via over-expression of Survivin.

Neuroprotective effects of a Smoothened receptor agonist against postoperative cognitive dysfunction by promoting autophagy in the dentate gyrus of aged rats.

Objectives: To investigate the effect of purmorphamine (PUR), a Shh co-receptor Smoothened (Smo) agonist, on postoperative cognitive dysfunction (POCD) rat models. Methods: Eighteen-month-old male Sprague-Dawley rats were subjected to intramedullary fixation of a tibial fracture with 7% chloral hydrate anesthesia to mimic human clinical surgery. PUR was administered via an intraperitoneal injection at a dose of 15mg/kg/day for 3 consecutive days at 6 h after surgery. The aged rats were sacrificed after performing a Morris water maze test 1, 3, and 7 days postoperatively to evaluate the expression of related proteins at the appointed time. Results: Compared to the POCD + vehicle group and sham + PUR group, the POCD + PUR group restored neurological deficit (P = 0.01). PUR administration induced upregulation of Shh expression on postoperative day 1 (P = 0.02), which continued on the third day (P = 0.008) but dropped by the 7th day (P = 0.03). Immunofluorescent analysis, similar to western blot analysis, showed a significant increase in the autophagy-marker LC3 (P = 0.006) as well as p62 degradation (P = 0.000) in the dentate gyrus of the aged rats (P = 0.000) after PUR treatment. Importantly, LC3 was mainly found in the presynaptic and postsynaptic membranes of the hippocampus. Conclusions: These results indicate a link between Shh and autophagy in the rat model of POCD, providing new insights into Shh signaling pathway-mediated mechanisms of neuroprotection and cognitive repair after POCD. It also provides a potential entry point for the development of clinical drugs.

Population-Based Incidence, Mortality, And Survival For Gastrointestinal Cancers During 2006-2016 In Wuhan, Central China.

OBJECTIVE: Incidence and mortality rates of malignant tumors in China are higher than global averages, especially for gastrointestinal (GI) cancers. To advance understanding of the epidemiology of GI cancers and to seek clues for cancer control, this study compared the incidence, mortality, and survival for GI cancers among residents of Wuhan (central China) and Chinese Americans. METHODS: A population-based study of cancer epidemiology was carried out on Wuhan residents and Chinese Americans. Data were collected from the Cancer Registry of Jiang'an District in Wuhan and the Surveillance, Epidemiology, and End Results (SEER) program. Joinpoint regression analyses were used to examine trends in the incidence and mortality of GI cancers in Wuhan. Furthermore, we estimated age-specific rates of incidence and mortality and survival rates of GI cancers in both populations. RESULTS: Among male GI cancer patients, mortality rates exhibited a significant increasing trend during 2006-2016 in Wuhan, with an annual percentage change (APC) of 7.4% (95% CI 1.7%-13.3%). Among female patients, the incidence of GI cancers showed a declining trend (APC -2.3%, 95% CI -3.4% to -1.3%) during 2006-2013, then escalated with an APC of 6.2% (95% CI 2.3%-10.2%) during 2013-2016. Both male and female patients with esophageal cancer in Wuhan experienced better survival than Chinese Americans. However, survival rates for the other three GI cancers in Wuhan were relatively lower than Chinese Americans. CONCLUSION: Escalating trends were observed in incidence among women and mortality among men with GI cancers. In addition, the survival rates of GI cancer patients in Wuhan were lower than Chinese Americans. As such, additional efforts are needed to control GI cancers in Wuhan, central China.

Nrf2/antioxidant defense pathway is involved in the neuroprotective effects of Sirt1 against focal cerebral ischemia in rats after hyperbaric oxygen preconditioning.

Sirtuin 1 (Sirt1) is a class III histone deacetylase involved in neuroprotection induced by hyperbaric oxygen preconditioning (HBO-PC) in animal models of ischemia. However, the underlying mechanisms remain to be illustrated. In the present study, rats exposed to middle cerebral artery occlusion (MCAO) were used to establish an ischemic stroke model. The infarct volume ratio, neurobehavioral score, and expressions of Sirt1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and superoxide dismutase 1 (SOD1) were evaluated at 7 days after reperfusion, and the level of malondialdehyde (MDA) was used to assess oxidative stress. HBO-PC increased the expression of Sirt1 and reduced infarct volume ratio and neurobehavioral deficit in MCAO rats. Meanwhile, HBO-PC also increased expression of Nrf2, HO-1, and SOD1 and decreased MDA content. Furthermore, either Sirt1 or Nrf2 knockdown by short interfering RNA (siRNA) inhibited the expression of Nrf2, HO-1, and SOD1 and eliminated the neuroprotective effects of HBO-PC. Taken together, the results suggest that the Nrf2/antioxidant defense pathway is involved in the long lasting neuroprotective effects of Sirt1 induced by HBO-PC against transient focal cerebral ischemia.