4'-O-methylbavachalcone alleviates ischemic stroke injury by inhibiting parthanatos and promoting SIRT3.

Cerebral ischemia-reperfusion injury (CIRI) can induce massive death of ischemic penumbra neurons via oxygen burst, exacerbating brain damage. Parthanatos is a form of caspase-independent cell death involving excessive activation of PARP-1, closely associated with intense oxidative stress following CIRI. 4'-O-methylbavachalcone (MeBavaC), an isoprenylated chalcone component in Fructus Psoraleae, has potential neuroprotective effects. This study primarily investigates whether MeBavaC can act on SIRT3 to alleviate parthanatos of ischemic penumbra neurons induced by CIRI. MeBavaC was oral gavaged to the middle cerebral artery occlusion-reperfusion (MCAO/R) rats after occlusion. The effects of MeBavaC on cerebral injury were detected by the neurological deficit score and cerebral infarct volume. In vitro, PC-12 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R), and assessed cell viability and cell injury. Also, the levels of ROS, mitochondrial membrane potential (MMP), and intracellular Ca2+ levels were detected to reflect mitochondrial function. We conducted western blotting analyses of proteins involved in parthanatos and related signaling pathways. Finally, the exact mechanism between the neuroprotection of MeBavaC and parthanatos was explored. Our results indicate that MeBavaC reduces the cerebral infarct volume and neurological deficit scores in MCAO/R rats, and inhibits the decreased viability of PC-12 cells induced by OGD/R. MeBavaC also downregulates the expression of parthanatos-related death proteins PARP-1, PAR, and AIF. However, this inhibitory effect is weakened after the use of a SIRT3 inhibitor. In conclusion, the protective effect of MeBavaC against CIRI may be achieved by inhibiting parthanatos of ischemic penumbra neurons through the SIRT3-PARP-1 axis.

Prognostic value of circulating tumor cells in esophageal cancer.

AIM: To perform a meta-analysis of the related studies to assess whether circulating tumor cells (CTCs) can be used as a prognostic marker of esophageal cancer. METHODS: PubMed, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival (OS). The meta-analysis was performed using the random effects model, with hazard ratio (HR), risk ratio (RR) and 95% confidence intervals (95%CIs) as effect measures. RESULTS: Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression (HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS (HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage (RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage (RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer. CONCLUSION: Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted.

TGF-ß1-509C/T polymorphism and the risk of ESCC in a Chinese Han population.

BACKGROUND: The studies investigating whether transforming growth factor (TGF)-ß1-509C/T polymorphism is associated with the risk of ESCC is inconsistent. METHODS: The TGF-ß1-509C/T genotypes were determined by using a polymerase chain reaction (PCR)-restriction fragment length polymorphism assay and DNA sequencing analysis. The differences in demographic variables and genotype distributions of TGF-ß1-509C/T polymorphism between ESCC patients and controls were calculated by Pearson's Chi square test. Associations between TGF-ß1-509C/T polymorphism genotypes and ESCC risk were estimated by OR and their 95% CIs computed using unconditional logistic regression model. RESULTS: There was a significant difference of TGF-ß1-509C/T polymorphism genotype distribution between ESCC group and control group (P<0.001). With the CC genotype as reference, the adjusted OR for CT genotype reached to 0.78 (95% CI: 0.65-0.89; P=0.041), and the adjusted OR for TT homozygous carriers was 0.52 (95% CI: 0.33-0.78; P=0.017). The T allele carriage also presented a lower risk for ESCC (adjusted OR=0.43; 95% CI, 0.29-0.71; P=0.009). CONCLUSION: TGF-ß1-509C/T polymorphism may contributes to ESCC susceptibility in Chinese population.

Nobiletin inhibited hypoxia-induced epithelial-mesenchymal transition of lung cancer cells by inactivating of Notch-1 signaling and switching on miR-200b.

Epithelial-mesenchymal transition (EMT) is an early step in the process of tumor metastasis. It is well known that tumor microenvironment affects malignancy in various carcinomas; in particular, that hypoxia induces EMT. Deregulated notch signaling also contributes a lot to the development of EMT in lung cancer. In this study, we investigated the use of Notch-1-inhibiting compound as novel therapeutic candidates to regulate hypoxia-induced EMT in lung cancer cells. According to previous screening, nobiletin was selected as a Notch-1 inhibitor. Hypoxia-induced EMT was characteristic of increased N-cadherin & vimentin expressions and decreased E-cadherin expressions. Treatment with nobiletin notably attenuated hypoxia-induced EMT, invasion and migration in H1299 cells, accompanied with reduced Notch-1, Jagged1/2 expressions and its downstream genes Hey-1 and Hes-1. Nobiletin treatment also promoted tumorsuppressive miR-200b level. Moreover, notch-1 siRNA prevented hypoxia-mediated cell migration and decreased Twist1, Snail1, and ZEB1/2 expressions, which are key EMT markers. Re-expression of miR-200b blocked hypoxia-induced EMT and cell invasion. Our findings suggest that downregulation of Notch-1 and reexpression of miR-200b by nobiletin might be a novel remedy for the therapy of lung cancer.

[Lung and heart-lung transplantation for Eisenmenger syndrome: report of 5 cases].

OBJECTIVE: To discuss the operative indications and peri-operational management of single lung transplantation (SLT) and heart-lung transplantation (HLT) for patients suffering from Eisenmenger's syndrome (ES). METHODS: From September.2002 to March.2006, four ES patients, 1 males and 3 females, aged 16 approximately 19, 2 with atrial septal defect and 2 with ventricular septal defect, underwent single right lung transplantation, and one patients, male, aged 43, who suffered heart failure secondary to an interventional occlusion for atrial septal defect underwent cardiac repair and HLT. RESULTS: Two patients, including the patient who received HLT and one, female, aged 15, who received SHT died of he died primary graft dysfunction on the 23rd day and 20th day post-operationally respectively. While the other 3 recipients kept a normal life for 5, 8, and 22 months respectively after operation with apparently decreased pulmonary artery pressure and improved cardiac-pulmonary functions. CONCLUSION: Lung transplantation companies with cardiac repair is effective in the therapy of ES. Donor-recipient matching in size, proper removal and protection of the donor lung, and appropriate postoperational management are the key procedures for those patients to survive.

[Effects of wrist-ankle acupuncture on functional states of the vegetative nerve in the recruit].

OBJECTIVE: To observe effects of wrist-ankle acupuncture on functional states of the vegetative nerve in the recruit. METHODS: Sixty recruits with the vegetative nerve balance index y > +0.56 determined with "Wenger-Chong Zhong Zhong Xiong"'s vegetative nerve balance factor assay were randomly divided into a treatment group and a control group. The treatment group were treated with wrist-ankle acupuncture and the control group with nothing. RESULTS: After treatment, 24 cases with y < +0.56 was found in the treatment group and 16 cases in the control group with a significant difference between the two groups (P < 0.05). CONCLUSION: Wrist-ankle acupuncture can better improve functional state of the vegetative nerve in the recruit.