Wnt-frizzled信号通路与心血管疾病关系的研究进展

Many researches have focused on the wnt- frizzled cascade in the recent years, while much work has been done in neoplastic diseases and embryology, the role of the wnt- frizzled signal transduction pathway in cardiovascular diseases has only recently begun to be explored. It plays a very important role in many physiological and pathophysiological processes, such as its transduction pathway, the healing after myocardial infarction, the proliferation, differentiation and orientation of cardiomyocytes, angiogenesis/neovascularization, cardiac hypertrophy and heart failure, the deposition of the extracellular matrix and so on. This article is aimed at its relation with myocardial infarction and the role of this pathway in cardiovascular diseases.     

The techniques of low density lipoprotein apheresis:a review

Today,the primary disease thatendangers the life of people in the world is car-diac disease.One of the main reasons that cause cardiovascular diseases isatherosclerosis ( AS) .Many researches show that elevated levels and oxidation oflow- density lipoprot…     

Implications of oral biofilms in medically at risk persons

There is the need to understand the composition of oral biofilms so that appropriate preventive and treatment regimens,including using appropriate antimicrobials,can be developed further.Additionally,when the systemic effects from specific microorganisms in oral biofilms are better understood,more targeted preventive treatment options may be recommended for persons at high risk for potential systemic diseases such as cardiovascular disease,and for aspiration pneumonia.Hence,the possible association between periodontopathic microorganisms,and also between cariogenic microorganisms in high caries risk persons,and systemic diseases requires further research involving metagenomic and large well-designed clinical studies.Effective preventive oral care is important for reducing potential systemic diseases.     

Relationship between Radiosensitivity and Telomere Length in Human Carcinoma Cell Lines

1 Introducion Radiotherapy has long been used as a curative treatment for many cancers. The sensitivity to the irradiation differs in various cancers, and relates to the individual radiotherapy protocol for each patient who suffered from malignancys. So what we will do is to find some definite indicators for radiosensitivity in order to make the individual treatment available. The length of telomere which is known as the "miototic clock" to determine the cell division ability[1]. Radiosensitivity is correlated with the cell division ability, therefore it maybe hypothesized that there is some intrinsic relationship between telomere length and radiosensitivity. In order to explore if the telomere length could be a valid indicator for radiosensitivity, we investigated the correlation between the radiosensitivity and telomere length with or without the pretreatment of azidothymidine (AZT), a telomerase inhibitor which can shorten the telomere, in several carcinoma cell lines.     

Heart＇omicsin＇AGEing （HOMAGE）：design,research objectives and characteristics of the common database

Heart failure is common in older people and its prevalence is increasing.The Heart ＇omics＇ in AGEing（HOMAGE） project aims to provide a biomarker approach that will improve the early diagnosis of heart failure.A large clinical database,based on（1） prospective population studies or（2） cross-sectional,prospective studies or randomized controlled trials（RCTs） of patients at risk for or with overt cardiovascular disease will be constructed to determine most promising ＇omics＇-based biomarkers to identify the risk of developing heart failure and/or comorbidities.Population studies,patient cohorts and RCTs are eligible for inclusion in the common database,if they received ethical approval to obtain and share data and have baseline information on cardiovascular risk factors.Currently,the HOMAGE database includes 43,065 subjects,from 20 studies in eight European countries,including healthy subjects from three population studies in France,Belgium and Italy（n = 7,124）,patients with heart failure（n = 4,312） from four cohorts in the UK,Spain and Switzerland and patients at high risk for cardiovascular disease（n = 31,629） in 13 cohorts.It is anticipated that more partners will join the consortium and enlarge the pooled data.This large merged database will be a useful resource with which to identify candidate biomarkers that play a role in the mechanism underlying the onset and progression of heart failure.     

Secondary metabolite credentials of Evolvulus alsinoides by high performance thin layer chromatography (HPTLC)

Plants and plant-based products are the bases of many modern pharmaceuticals that are current in use today for various diseases.The aim of the study was to investigate the biochemical constituents and high performance thin layer chromatography(HPTLC) finger printing of the ethanolic extract of Evolvulus alsinoides.Phytochemical screening was done by standard procedures and HPTLC method was also established to analyze alkaloids,flavonoids and phenolic compounds from the ethanolic extract of Evolvulus alsinoides.Preliminary phytochemical screening showed that ethanol extracted more secondary metabolites than other solvents.HPTLC fingerprinting analysis showed the presence of various alkaloids,flavonoids and phenols(quercetin) in the ethanolic extract.It can be concluded that Evolvulus alsinoides may serve as a source of potent antioxidants that may be used in the prevention of various diseases such as cancer,diabetes and cardiovascular diseases due to the presence of phenolic compounds.HPTLC finger print of Evolvulus alsinoides may be useful in the differentiation of the species from adulterants and act as a biochemical marker for this medicinally important plant in the pharmaceutical industry and plant systematic studies.     

Treatment of Chronic Periodontal Defects with Tissue Engineering: A Pilot Study in Dogs

1 IntroductionThe most desirable goal of periodontal therapy is to restore the architecture and function of the periodontal tissues, which lost due to inflammatory periodontal diseases or trauma. Although a variety of periodontal procedures advocated, the regenerative and reconstructive therapy with more predictability and less technique sensitivity is still lacking.Periodontal tissue engineering is becoming a new paradigm for periodontal regeneration. The in vitro experiments on periodontal t…     

Nigerian Population Research on Environment,Gene and Health （NIPREGH）-objectives and protocol

Sub-Saharan Africa is currently undergoing an epidemiological transition from a disease burden largely attributable to communicable diseases to that resulting from a combination of both communicable and chronic non-communicable diseases.Data on chronic disease incidence,lifestyle,environmental and genetic risk factors are sparse in this region.This report aimed at providing relevant information in respect to risk factors that increase blood pressure and lead to development of intermediate cardiovascular phenotypes.We presented the rationale,objectives and key methodological features of the Nigerian Population Research on Environment,Gene and Health（NIPREGH） study.The challenges encountered in carrying out population study in this part of the world and the approaches at surmounting them were also presented.The preliminary data as at 20 November 2013 showed that out of the 205 individuals invited starting from early April 2013,160（72 women） consented and were enrolled;giving a response rate of 78%.Participants＇ age ranged from 18 to 80 years,with a mean（SD） of 39.8（12.4） years and they were of 34 different ethnic groups spread over 24 states out of the 36 states that constitute Nigeria.The mean（SD） of office and home blood pressures were 113.0（15.2） mm Hg systolic,73.5（12.5） mm Hg diastolic and 117.3（15.0） mm Hg systolic,and 76.0（9.6） mm Hg diastolic,respectively.Forty-three（26.8%） participants were hypertensive and 8（5.0%） were diabetic.In addition to having the unique potential of recruiting a cohort that is a true representative of the entire Nigerian population,NIPREGH is feasible and the objectives realisable.     

心肌梗死后心室电重构的细胞和分子生物学机制

Arrhythmia is common in cardiovascular diseases, especially after myocardial infarction. This article reviews the electrophysiologic changes following myocardial infarction at different phases. Modulations of ion channel function that might contribute to electrical remodeling, such as cellular (autocrine/paracrine) factors and regulators of ion channel gene, are discussed. Unresolved problems in ventricular electrical remodeling after myocardial infarction are also considered.     

端粒耗损与心血管疾病

心血管疾病一直被认为是与年龄相关的退行性疾病,端粒随年龄增长而变短,是细胞老化的标志.最近,越来越多的研究表明端粒长度缩短与心血管疾病发生发展有关.该文仅就端粒耗损与心血管疾病相关性的研究进展作一综述,旨在为今后心血管疾病的预防和治疗提供新的思路.     

Telomerase activation: A potential key modulator for human healthspan and longevity

The elderly population is increasing progressively. Along with this increase the number of age related diseases, such as cardiovascular, neurodegenerative diseases, metabolic impairment and cancer, is also on the rise thereby negatively impacting the burden on health care systems. Telomere shortening and dysfunction results in cellular senescence, an irreversible proliferative arrest that has been suggested to promote organismal aging and disabling age-related diseases. Given that telomerase, the enzyme responsible for maintaining telomere lengths, is not expressed at levels sufficient to prevent telomere shortening in most of our cells, telomeres progressively erode with advancing age. Telomerase activation, therefore, might serve as a viable therapeutic strategy to delay the onset of cellular senescence, tissue dysfunction and organismal decline. Here we analyze the more recent findings in telomerase activation as a potential key modulator for human healthspan and longevity.     

血管老化在动脉粥样硬化中的研究进展

血管老化是血管的结构和功能随年龄增长呈现年龄依赖性的退行性改变,可导致心血管疾病的患病风险显著增加.动脉粥样硬化是多种心血管疾病的病理生理基础,血管老化在动脉粥样硬化的发生发展中发挥重要作用.有效评估血管老化对动脉粥样硬化性心血管疾病的临床诊疗意义重大.本文总结了血管老化的结构和功能性变化,阐述血管老化过程中血管细胞端...     

Telomere length and cardiovascular aging: the means to the ends?

Epidemiologic and other evidence clearly indicates that peripheral blood leukocyte telomere length, a systemic marker for biological aging, can be useful as a cardiovascular aging biomarker. Although telomere biology might yield new insights into the underlying molecular biology of vascular aging and even radically improve current cardiovascular risk stratification, the specific nature of the association between telomere length and cardiovascular disease still remains to be elucidated. Here, we review several candidate hypotheses and critically review supporting and contesting scientific evidence for the underlying theories. For each hypothesis, we discuss the potential implications. We conclude that the most promising theory is based on an acceleration of the telomere attrition rate due to cardiovascular aging related factors, possibly complemented by telomere mediated hematopoietic senescence.     

Telomeres,sex, reactive oxygen species,and human cardiovascular aging

By undergoing erosion with each replicative cycle, telomeres chronicle the replicative history of human somatic cells in vitro and in vivo. In human beings the telomere is relatively short, inversely correlated with age, highly heritable, and longer in women than men. However, it is not established whether the dynamics of telomere attrition in vivo has a role in the biology of human aging. Telomere attrition may be modified by reactive oxygen species, the biology of which is governed by processes that are influenced by sex. Indices of cardiovascular aging in humans are correlated with telomere length and this relationship is characterized by sexual dimorphism. In the final analysis, the biology of reactive oxygen species may offer a common explanation for some interindividual variation in cardiovascular aging and age-dependent telomere attrition in humans.     

Pharmacologic manipulation of the ataxia-telangiectasia mutated gene product as an intervention in age-related disease

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by progressive ataxia, elevated cancer incidence, and premature aging. A-T cells, Atm-deficient mice, and individuals with A-T show increased oxidant sensitivity, genomic instability, altered IGF-1 and p53 signaling, and rapid telomere shortening compared to normal controls. The gene mutated in A-T, ATM, regulates DNA repair, IGF-1 and p53 signaling, age pigment removal, antioxidant capacity, and telomere maintenance - pathways involved in and often attenuated with aging. Interestingly, flavonoids with chemopreventative effects, such as quercetin, genistein, and epigallocatechin gallate activate ATM. Since ATM activates pathways which increase genomic stability, oxidant resistance, and/or telomere stability, and since many diseases of old age (i.e., cancer, cardiovascular and neurodegenerative disease), result from attenuation of these pathways, pharmacologic manipulation of ATM activity via flavonoid intake may prove useful in slowing the appearance of age-associated disease.     

Reduced telomere length variation in healthy oldest old

Telomeres protect against DNA degradation at the ends of linear chromosomes. The number of telomere repeats is reduced over time in human aging. Using flow FISH we have assessed telomere length in 134 exceptionally healthy seniors aged 85 or older who have never been diagnosed with cancer, cardiovascular disease, major pulmonary disease, diabetes or Alzheimer disease (the ‘Super-seniors’) and 47 randomly-ascertained mid-life individuals aged 40-50 years. We compared their telomere lengths to a reference interval based on 400 individuals aged 1-100 years and show that Super-seniors do not have exceptionally long telomeres for their age. Consistent with the known trend of telomere shortening over time; however, they have shorter telomeres than the younger control group.Furthermore, we show that variability in telomere length was lower in the Super-seniors than in the mid-life controls or the reference data. Reduced telomere length variation was observed for lymphocytes, CD45RA-positive T-cells and memory T-cells. These results suggest that individuals, some types of their somatic cells, or both, may be selected for an optimal rather than extreme telomere length. Selection of individuals and/or cells that have an optimal telomere repeat length could contribute to disease resistance and promote healthy aging.     

Telomeres and frailty

Associations between telomere length and various chronic diseases associated with ageing have led to the suggestion that telomere length may be an ageing biomarker. At the clinical level, the suggestion of using measurements of frailty as a measure of biological ageing has also been suggested. This study examines the hypothesis that telomere shortening may form the biological basis for frailty, using data obtained from a health survey of 2000 men and women aged 65 years and over, living in the community, and followed up for 4 years to determine survival. Frailty was measured using the frailty index, a summation of deficits covering physical, psychological, and functional domains. Telomere length was measured in 976 men and 1030 women, using real-time quantitative polymerase chain reaction. Women were more frail than men but had longer telomere length. In men only, there was a negative association between telomere length and age and a positive association between frailty index and mortality after adjusting for age. There was no correlation between telomere length and frailty index in either sex. While telomere length may be a biomarker of cellular senescence, this relationship may not be extrapolated to the functional level represented by the frailty phenotype.     

Stress and telomere shortening: Insights from cellular mechanisms

Short telomeres confer risk of degenerative diseases. Chronic psychological stress can lead to disease through many pathways, and research from in vitro studies to human longitudinal studies has pointed to stress-induced telomere damage as an important pathway. However, there has not been a comprehensive model to describe how changes in stress physiology and neuroendocrine pathways can lead to changes in telomere biology. Critically short telomeres or the collapse of the telomere structure caused by displacement of telomere binding protein complex shelterin elicit a DNA damage response and lead to senescence or apoptosis. In this narrative review, we summarize the key roles glucocorticoids, reactive oxygen species (ROS) and mitochondria, and inflammation play in mediating the relationship between psychological stress and telomere maintenance. We emphasis that these mediators are interconnected and reinforce each other in positive feedback loops. Telomere length has not been studied across the lifespan yet, but the initial setting point at birth appears to be the most influential point, as it sets the lifetime trajectory, and is influenced by stress. We describe two types of intergenerational stress effects on telomeres – prenatal stress effects on telomeres during fetal development, and ‘telotype transmission” –the directly inherited transmission of short telomeres from parental germline. It is clear that the initial simplistic view of telomere length as a mitotic clock has evolved into a far more complex picture of both transgenerational telomere influences, and of interconnected molecular and cellular pathways and networks, as hallmarks of aging where telomere maintenance is a key player interacting with mitochondria. Further mechanistic investigations testing this comprehensive model of stress mediators shaping telomere biology and the telomere-mitochondrial nexus will lead to better understanding from cell to human lifespan aging, and could lead to anti-aging interventions.