红背山麻杆叶的化学成分研究(Ⅱ)——黄酮和苯乙醇苷类化合物

采用80％丙酮提取物的水萃取部位,利用凝胶、MCI、反相碳18、及 Toyopearl Butyl-650C 柱色谱进行分离纯化得到7个黄酮和3个苯乙醇苷类化合物。根据化合物的波谱数据分析鉴定为槲皮素(1)、槲皮苷(2)、异懈皮苷(3)、芦丁(4)、异牡荆素(5)、牡荆素(6)、木犀草素-7-O-α-L-鼠李糖(1→6)-β-D-葡萄糖苷(7)、2-phenethylβ-D-glucoside(8)、icariside D1(9)、2-苯乙基-D-芸香甙(10)。其中化合物1-3、5-6、8-10为首次从本属植物中分离得到。     

Src Regulates the Activity of the ING1 Tumor Suppressor

The INhibitor of Growth 1 (ING1) is stoichiometric member of histone deacetylase (HDAC) complexes and functions as an epigenetic regulator and a type II tumor suppressor. It impacts cell growth, aging, apoptosis, and DNA repair, by affecting chromatin conformation and gene expression. Down regulation and mislocalization of ING1 have been reported in diverse tumor types and Ser/Thr phosphorylation has been implicated in both of these processes. Here we demonstrate that both in vitro and in vivo, the tyrosine kinase Src is able to physically associate with, and phosphorylate ING1, which results in a nuclear to cytoplasmic relocalization of ING1 in cells and a decrease of ING1 stability. Functionally, Src antagonizes the ability of ING1 to induce apoptosis, most likely through relocalization of ING1 and down regulation of ING1 levels. These effects were due to both kinase-dependent and kinase-independent properties of Src, and were most apparent at elevated levels of Src expression. These findings suggest that Src may play a major role in regulating ING1 levels during tumorigenesis in those cancers in which high levels of Src expression or activity are present. These data represent the first report of tyrosine kinase-mediated regulation of ING1 levels and suggest that kinase activation can impact chromatin structure through the ING1 epigenetic regulator.     

Association between depression and hospital outcomes among older men

Background:

Studies that have investigated the relation between depression and the type, nature, extent and outcome of general hospital admissions have been limited by their retrospective designs and focus on specific clinical populations. We explored this relation prospectively in a large, community-based sample of older men.

Methods:

A cohort of 5411 men aged 69 years and older enrolled in the Health in Men Study was assessed at baseline for depressive symptoms, defined as a score of 7 or higher on the 15-item Geriatric Depression Scale. Participants were followed for 2 years for occurrence and number of hospital admissions, type of hospital admission, length of hospital stay and inpatient death as recorded in the Western Australian Data Linkage System.

Results:

Of 339 men with depressive symptoms, 152 (44.8%) had at least 1 emergency hospital admission, compared with 1164 of 5072 (22.9%) nondepressed men (p < 0.001). In multivariate analyses, the presence of depressive symptoms was a significant independent predictor of hospital admission (hazard ratio 1.67, 95% confidence interval [CI] 1.38–2.01), number of hospital admissions (incidence rate ratio [IRR] 1.22, 95% CI 1.07–1.39) and total length of hospital stay (IRR 1.65, 95% CI 1.36–2.01).

Interpretation:

Participants with depressive symptoms were at higher risk of hospital admission for nonpsychiatric conditions and were more likely to have longer hospital stays and worse hospital outcomes, compared with nondepressed participants. These results highlight the potential to target this high-risk group to reduce the burden of health care costs in an aging population.Older people are the most frequent users of health services, and the progressive aging of the world’s population may lead to a saturation of available services. Therefore, we must find ways to reduce preventable admissions to hospital and uncover the factors associated with potentially preventable use of health services. An association between depression and hospital admission for nonpsychiatric conditions has been postulated, although the data have been limited to specific clinical populations and the interpretation of the results hampered by the retrospective study design and the use of self-reported outcomes.^1–8 Consequently, these findings cannot be easily generalized or used to develop data-driven interventions.We addressed this gap in the literature by using a community-based population survey with prospective data linkage to measure important health-related outcomes. Our main objective was to investigate whether community-dwelling older men with depressive symptoms were more likely than nondepressed men to be admitted to general hospitals. Our other aims were to determine whether the long-term clinical outcomes of these 2 groups differed in relation to the number of future hospital admissions, length of hospital stay and inpatient deaths.     

Dynamics of the "popcorn" Wolbachia infection in outbred Aedes aegypti informs prospects for mosquito vector control

Forty percent of the world's population is at risk of contracting dengue virus, which produces dengue fever with a potentially fatal hemorrhagic form. The wMelPop Wolbachia infection of Drosophila melanogaster reduces life span and interferes with viral transmission when introduced into the mosquito Aedes aegypti, the primary vector of dengue virus. Wolbachia has been proposed as an agent for preventing transmission of dengue virus. Population invasion by Wolbachia depends on levels of cytoplasmic incompatibility, fitness effects, and maternal transmission. Here we characterized these traits in an outbred genetic background of a potential target population of Ae. aegypti using two crossing schemes. Cytoplasmic incompatibility was strong in this background, and the maternal transmission rate of Wolbachia was high. The infection substantially reduced longevity of infected adult females, regardless of whether adults came from larvae cultured under high or low levels of nutrition or density. The infection reduced the viability of diapausing and nondiapausing eggs. Viability was particularly low when eggs were laid by older females and when diapausing eggs had been stored for a few weeks. The infection affected mosquito larval development time and adult body size under different larval nutrition levels and densities. The results were used to assess the potential for wMelPop-CLA to invade natural populations of Ae. aegypti and to develop recommendations for the maintenance of fitness in infected mosquitoes that need to compete against field insects.     

Mortality among People with Severe Mental Disorders Who Reach Old Age: A Longitudinal Study of a Community-Representative Sample of 37892 Men

Background

Severe mental illnesses are leading causes of disability worldwide. Their prevalence declines with age, possibly due to premature death. It is unclear, however, if people with severe mental disorders who reach older age still have lower life expectancy compared with their peers and if their causes of death differ.

Methods and Findings

Cohort study of a community-representative sample of 37892 Australian men aged 65–85 years in 1996–1998. Follow up was censored on the 31st December 2010. Lifetime prevalence of schizophrenia spectrum, bipolar, depressive and alcohol-induced disorder was established through record linkage. A subsample of 12136 consented to a face-to-face assessment of sociodemographic, lifestyle and clinical variables. Information about causes of death was retrieved from the Australian Death Registry. The prevalence of schizophrenia spectrum, bipolar, depressive and alcohol-induced disorders was 1.2%, 0.3%, 2.5% and 1.8%. The mortality hazard for men with a severe mental disorder was 2.3 and their life expectancy was reduced by 3 years. Mortality rates increased with age, but the gap between men with and without severe mental disorders was not attenuated by age. Cardiovascular diseases and cancer were the most frequent causes of death. The excess mortality associated with severe mental disorders could not be explained by measured sociodemographic, lifestyle or clinical variables.

Conclusions

The excess mortality associated with severe mental disorders persists in later life, and the causes of death of younger and older people with severe mental disorders are similar. Hazardous lifestyle choices, suboptimal access to health care, poor compliance with treatments, and greater severity of medical comorbidities may all contribute to this increased mortality. Unlike young adults, most older people will visit their primary care physician at least once a year, offering health professionals an opportunity to intervene in order to minimise the harms associated with severe mental disorders.