Xu J.,Hebei United University |
Tian W.,Hebei United University |
Ma X.,Workers Hospital |
Guo J.,Hebei United University |
And 4 more authors.
Cell Biochemistry and Biophysics | Year: 2011
Although Akt is reported to play a role in morphine's cardioprotection, little is known about the mechanism underlying morphine-induced Akt activation. This study aimed to define the molecular mechanism underlying morphine-induced Akt activation and to determine if the mechanism contributes to the protective effect of morphine on ischemia/reperfusion injury. In cardiac H9c2 cells, morphine increased Akt phosphorylation at Ser 473, indicating that morphine upregulates Akt activity. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling, was not involved in the action of morphine on Akt activity. Morphine decreased the activity of PP2A, a major protein Ser/Thr phosphatase, and inhibition of PP2A with okadaic acid (OA) mimicked the effect of morphine on Akt activity. The effects of morphine on PP2A and Akt activities were inhibited by the reactive oxygen species (ROS) scavenger N-(2-mercaptopropionyl)glycine (MPG) and the mitochondrial K ATP channel closer 5-hydroxydecanoate (5HD). In support, morphine could produce ROS and this was reversed by 5HD. Finally, the cardioprotective effect of morphine on ischemia-reperfusion injury was mimicked by OA but was suppressed by 5HD or MPG, indicating that protein phosphatases and ROS are involved in morphine's protection. In conclusion, morphine upregulates Akt activity by inactivating protein Ser/Thr phosphatases via ROS, which may contribute to the cardioprotective effect of morphine. © 2011 Springer Science+Business Media, LLC.
Munoz C.,University of Antofagasta |
Perez M.,University of Antofagasta |
Orrego P.R.,University of Antofagasta |
Osorio L.,University of Antofagasta |
And 14 more authors.
International Journal for Parasitology | Year: 2012
In this work, evidence for a critical role of Trichomonas vaginalis protein phosphatase 1 gamma (TvPP1γ) in proliferation and attachment of the parasite to the mammalian cell is provided. Firstly, proliferation and attachment of T. vaginalis parasites to HeLa cells was blocked by calyculin A (CA), a potent PP1 inhibitor. Secondly, it was demonstrated that the enzyme activity of native and recombinant TvPP1γ proteins was inhibited by CA. Thirdly, reverse genetic studies confirmed that antisense oligonucleotides targeted to PP1γ but not PP1α or β inhibited proliferation and attachment of trichomonads CA-treated parasites underwent cytoskeletal modifications, including a lack of axostyle typical labelling, suggesting that cytoskeletal phosphorylation could be regulated by a CA-sensitive phosphatase where the role of PP1γ could not be ruled out. Analysis of subcellular distribution of TvPP1γ by cell fractionation and electron microscopy demonstrated the association between TvPP1γ and the cytoskeleton. The expression of adhesins, AP120 and AP65, at the cell surface was also inhibited by CA. The concomitant inhibition of expression of adhesins and changes in the cytoskeleton in CA-treated parasites suggest a specific role for PP1γ -dependent dephosphorylation in the early stages of the host-parasite interaction. Molecular modelling of TvPP1γ showed the conservation of residues critical for maintaining proper folding into the gross structure common to PP1 proteins. Taken together, these results suggest that TvPP1γ could be considered a potential novel drug target for treatment of trichomoniasis. © 2012 Australian Society for Parasitology Inc..
Song W.-G.,Workers Hospital |
Wang Y.-F.,Workers Hospital |
Wang R.-L.,Workers Hospital |
Qu Y.,Hebei University |
And 5 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2013
Objective: This work aims to investigate the therapeutic regimen of brain metastatic cancers and the relationship between clinical features and prognosis. Methods: Clinical data of 184 patients with brain metastatic cancers were collected and analysed for the relationship between survival time and age, gender, primary diseases, quantity of brain metastatic foci, their position, extra cranial lesions, and therapeutic regimens. Results: The average age of onset was 59.1 years old. The median survival time (MST) was 15.0 months, and the patients with breast cancer as the primary disease had the longest survival time. Females had a longer survival time than males. Patients with meningeal metastasis had extremely short survival time. Those with less than 3 brain metastatic foci survived longer than patients with more than 3. The MST of patients receiving radiotherapy only and the patients receiving chemotherapy only were all 10.0 months while the MST of patients receiving combination therapy was 16.0 months. Multiple COX regression analysis demonstrated that gender, primary diseases, and quantity of brain metastatic foci were independent prognostic factors for brain metastatic cancers. Conclusions: Chemotherapy is as important as radiotherapy in the treatment of brain metastatic cancer. Combination therapy is the best treatment mode. Male gender, brain metastatic cancers originating in the gastrointestinal tract, more than 3 metastatic foci, and involvement of meninges indicate a worse prognosis.
Chen H.,Capital Medical University |
Dai J.,Capital Medical University |
Dai J.,Beijing Neurosurgery Institute |
Zhang X.,Capital Medical University |
And 18 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2013
The present study attempted to explore modulated hypothalamus-seeded resting brain network underlying the cardiovascular system in primary hypertensive patients after short-term acupuncture treatment. Thirty right-handed patients (14 male) were divided randomly into acupuncture and control groups. The acupuncture group received a continuous five-day acupuncture treatment and undertook three resting-state fMRI scans and 24-hour ambulatory blood pressure monitoring (ABPM) as well as SF-36 questionnaires before, after, and one month after acupuncture treatment. The control group undertook fMRI scans and 24-hour ABPM. For verum acupuncture, average blood pressure (BP) and heart rate (HR) decreased after treatment but showed no statistical differences. There were no significant differences in BP and HR between the acupuncture and control groups. Notably, SF-36 indicated that bodily pain (P = 0.005) decreased and vitality (P = 0.036) increased after acupuncture compared to the baseline. The hypothalamus-related brain network showed increased functional connectivity with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes. In conclusion, short-term acupuncture did not decrease BP significantly but appeared to improve body pain and vitality. Acupuncture may regulate the cardiovascular system through a complicated brain network from the cortical level, the hypothalamus, and the brainstem. © 2013 Hongyan Chen et al.