Age-Associated Sirtuin 1 Reduction in Vascular Smooth Muscle Links Vascular Senescence and Inflammation to Abdominal Aortic Aneurysm.

RATIONALE: Uncontrolled growth of abdominal aortic aneurysms (AAAs) is a life-threatening vascular disease without an effective pharmaceutical treatment. AAA incidence dramatically increases with advancing age in men. However, the molecular mechanisms by which aging predisposes individuals to AAAs remain unknown. OBJECTIVE: In this study, we investigated the role of SIRT1 (Sirtuin 1), a class III histone deacetylase, in AAA formation and the underlying mechanisms linking vascular senescence and inflammation. METHODS AND RESULTS: The expression and activity of SIRT1 were significantly decreased in human AAA samples. SIRT1 in vascular smooth muscle cells was remarkably downregulated in the suprarenal aortas of aged mice, in which AAAs induced by angiotensin II infusion were significantly elevated. Moreover, vascular smooth muscle cell-specific knockout of SIRT1 accelerated angiotensin II-induced formation and rupture of AAAs and AAA-related pathological changes, whereas vascular smooth muscle cell-specific overexpression of SIRT1 suppressed angiotensin II-induced AAA formation and progression in Apoe-/- mice. Furthermore, the inhibitory effect of SIRT1 on AAA formation was also proved in a calcium chloride (CaCl2)-induced AAA model. Mechanistically, the reduction of SIRT1 was shown to increase vascular cell senescence and upregulate p21 expression, as well as enhance vascular inflammation. Notably, inhibition of p21-dependent vascular cell senescence by SIRT1 blocked angiotensin II-induced nuclear factor-κB binding on the promoter of monocyte chemoattractant protein-1 and inhibited its expression. CONCLUSIONS: These findings provide evidence that SIRT1 reduction links vascular senescence and inflammation to AAAs and that SIRT1 in vascular smooth muscle cells provides a therapeutic target for the prevention of AAA formation.

High expression of COX5B is associated with poor prognosis in breast cancer.

BACKGROUND: Cytochrome c oxidase subunit VB (COX5B), a subunit of mammalian COX, takes roles in COX assembling and functions. Online database predicts high COX5B transcription may be associated with worse disease-free survival (DFS). However, the clinical implications of COX5B in breast cancer remain unclear. METHODS: We carried out immunohistochemistry on tissue microarrays of 244 patients with invasive ductal breast carcinoma to detected COX5B expression. RESULTS: Our results suggest that COX5B protein level might be associated with tumor size. COX5B overexpression indicated a worse DFS (p < 0.05) in breast cancer. Furthermore, high COX5B expression may act as an independent factor for worse DFS in breast cancer. CONCLUSIONS: Cumulatively, our findings suggest that COX5B might serve as an important prognostic factor for breast cancer.

Gypenosides protected the neural stem cells in the subventricular zone of neonatal rats that were prenatally exposed to ethanol.

Fetal alcohol spectrum disorder (FASD) can cause severe mental retardation in children who are prenatally exposed to ethanol. The effects of prenatal and early postnatal ethanol exposure on adult hippocampal neurogenesis have been investigated; however, the effects of prenatal ethanol exposure on the subventricular zone (SVZ) have not. Gypenosides (GPs) have been reported to have neuroprotective effects in addition to other bioactivities. The effects of GPs on neural stem cells (NSCs) in the FASD model are unknown. Here, we test the effect of prenatal ethanol exposure on the neonatal SVZ, and the protection potential of GPs on NSCs in FASD rats. Our results show that prenatal ethanol exposure can suppress the cell proliferation and differentiation of neural stem cells in the neonatal SVZ and that GPs (400 mg/kg/day) can significantly increase the cell proliferation and differentiation of neural stem cells inhibited by ethanol. Our data indicate that GPs have neuroprotective effects on the NSCs and can enhance the neurogenesis inhibited by ethanol within the SVZ of neonatal rats. These findings provide new evidence for a potential therapy involving GPs for the treatment of FASD.

[Research progress on effect of coumarins compounds in anti-tumor].

Coumarins are a group of important natural compounds, and have been found to have multi-biological activities such as anti-HIV, anti-tumor, anti-hypertension, anti-arrhythmia, anti-osteoporosis, assuaging pain, preventing asthma and antisepsis. One of which is its anti-tumor effect and that is a research focus on. Therefore, we believe that it is necessaryto carry out further studies on the effect of coumarins compounds in anti-tumor. Investigation should emphasize on improving techniques for extraction and separation, searching the effective precursory compound, and synthesizing and screening out courmarin derivatives with high activity and low toxicity. Here the recent research progress in anti-tumor effect of coumarins compounds is reviewed.

Resistance of Seven Cabbage Cultivars to Green Peach Aphid (Hemiptera: Aphididae).

The green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae), is an important pest of many crops in the world and a vector of more than 100 plant viruses. It is a major pest of Brassica vegetables such as Chinese cabbage in northern China. Chemical control is extensively used to manage this aphid around the world; however, development of insecticide resistance has been a major obstacle facing growers. Host plant resistance in Chinese cabbage against M. persicae has not been reported yet. In this study, we investigated the resistance categories in seven Chinese cabbage cultivars against M. persicae. The resistance categories of these cultivars included antixenosis, antibiosis, and tolerance related to leaf color and wax content. The cultivar 'Yuanbao' had antibiotic and tolerance effects on the aphid. The rate of intrinsic increase (rm) of M. persicae was lower on Yuanbao compared with the other six cultivars. Yuanbao also had the highest antibiosis against the aphid. The aphid preferred 'Qingan 80', which had the highest wavelength (green) in leaf color. The highest wax content was found in Yuanbao, which had a significantly negative correlation with the preference of M. persicae. The cabbage cultivar Yuanbao was resistant to M. persicae and could be used in the development of integrated pest management (IPM) programs against the aphid in the field.

UHRF1 promotes breast cancer progression by suppressing KLF17 expression by hypermethylating its promoter.

UHRF1 is an epigenetic regulator and perform pivotal functions in cell tumorigenesis. We found UHRF1 is increased in breast cancer and patients with high UHRF1 levels have poorer prognoses than those with low UHRF1 levels. However, the underlying mechanisms remain largely unknown. Here, we found overexpression UHRF1 indeed promoted cell proliferation and migration, whereas its downregulation had the opposite functions. In vivo, UHRF1 also accelerated tumor growth. Mechanistically, microarrays were performed in MDA-MB-231 sh-UHRF1 and NC cells and KLF17, with rich CpG islands on its promoter region, finally caused our attention. Then, the expression of UHRF1 and KLF17 was testified negatively correlated in breast cancer cell lines and tissues. Additionally, the inhibition of cell proliferation and migration by UHRF1 depletion can be rescued by KLF17 silencing, suggesting KLF17 is downstream gene of UHRF1. The potential mechanism is that overexpression UHRF1 increased methylation of CpG nucleotides on KLF17 promoter, while UHRF1 silence decreased methylation. Collectively, our results demonstrated that increased UHRF1 can promote breast cancer cell proliferation and migration via silencing of KLF17 expression through CpG island methylation on its promoter.

Comparison of patterns and prognosis among distant metastatic breast cancer patients by age groups: a SEER population-based analysis.

To investigate the effects of age at diagnosis on metastatic breast cancer and patients' prognosis, we collected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. We finally identified 4932 eligible metastatic breast cancer patients diagnosed between 2010-2013, including 850 younger patients (<50 years), 2,540 middle-aged patients (50-69 years) and 1,542 elder patients (>69 years). The results revealed that in stage IV patients, elder patients were more likely to have lung metastasis (P < 0.001) and less likely to have only distant lymphatic spread (P = 0.004). Higher proportion of younger (34.9%) and middle-aged (36.2%) patients had multiple metastatic sites than elder patients (28.3%) (P < 0.001). In survival analysis, younger patients presented the best prognosis, while elder patients had the worst both in overall survival (χ2 = 121.9, P < 0.001) and breast cancer-specific survival (χ2 = 69.8, P < 0.001). Age at diagnosis was an independent prognostic factor for metastatic breast cancer patients. Moreover, patients with bone metastasis only had superior survival compared to other metastatic patients (P < 0.001). Brain metastasis only group and multiple sites metastasis group had the poorest prognosis (P < 0.05). We hope the results will provide insights into a better understanding of distant metastatic breast cancer.

Clinicopathological characteristics and survival outcomes of male breast cancer according to race: A SEER population-based study.

To investigate the clinicopathological characteristics and survival outcomes of breast cancer in the male population, 8,607 cases of patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database, including white males (n = 7122), black males (n = 1111), and other males (American Indian/AK Native, Asian/Pacific Islander) (n = 374). Black male breast cancer patients were more likely to be in stages II-IV and have more advanced tumors. The rate of lymph node (LN) involvement at diagnosis was higher in black men than in whites and others. The ER- and PR-positive rates were lower in black men than in whites and others. The distant metastasis rate was higher in blacks than in whites and others. Furthermore, the overall survival (OR) rates and breast cancer-specific survival rates were significantly poorer in blacks than in whites and others (χ2 = 29.974, P < 0.001; χ2 = 7.285, P = 0.026, respectively). In a multivariate analysis, the results showed that race could also be a prognostic indicator (P < 0.001). Moreover, significant differences were also observed in OS among 1:1:1 matched white, black, and other groups (P < 0.001). Differences in outcomes may be partially explained by differences in tumor grades, LN status, and ER and PR status between the 3 groups. This study might provide insights into a better understanding of male breast cancer.

Calorie restriction protects against experimental abdominal aortic aneurysms in mice.

Abdominal aortic aneurysm (AAA), characterized by a localized dilation of the abdominal aorta, is a life-threatening vascular pathology. Because of the current lack of effective treatment for AAA rupture, prevention is of prime importance for AAA management. Calorie restriction (CR) is a nonpharmacological intervention that delays the aging process and provides various health benefits. However, whether CR prevents AAA formation remains untested. In this study, we subjected Apoe-/- mice to 12 wk of CR and then examined the incidence of angiotensin II (AngII)-induced AAA formation. We found that CR markedly reduced the incidence of AAA formation and attenuated aortic elastin degradation in Apoe-/- mice. The expression and activity of Sirtuin 1 (SIRT1), a key metabolism/energy sensor, were up-regulated in vascular smooth muscle cells (VSMCs) upon CR. Importantly, the specific ablation of SIRT1 in smooth muscle cells abolished the preventive effect of CR on AAA formation in Apoe-/- mice. Mechanistically, VSMC-SIRT1-dependent deacetylation of histone H3 lysine 9 on the matrix metallopeptidase 2 (Mmp2) promoter was required for CR-mediated suppression of AngII-induced MMP2 expression. Together, our findings suggest that CR may be an effective intervention that protects against AAA formation.