A new novel mutation in FBN1 causes autosomal dominant Marfan syndrome in a Chinese family

Purpose: Screening of mutations in the fibrillin-1 (FBN1) gene in a Chinese family with autosomal dominant Marfan syndrome (MFS). Methods: It has been reported that FBN1 mutations account for approximately 90% of Autosomal Dominant MFS. FBN1 mutations were analyzed in a Chinese family of 36 members including 13 MFS patients. The genomic DNAs from blood leukocytes of the patients and their relatives were isolated and the entire coding region of FBN1 was amplified by PCR. The sequence of FBN1 was dertermined with an ABI 3100 Genetic Analyzer. Results: A previously unreported the missense mutation G214S (caused by a 640 A -> G heterozygous change) in FBN1 was identified in the Chinese family. The mutation was associated with the disease phenotype in patients, but not detected in their relatives or in the 100 normal controls. Conclusions: This is the first report of molecular characterization of FBN1 in the MFS family of Chinese origin. Our results expand the spectrum of FBN1 mutations causing MFS and further confirm the role of FBN1 in the pathogenesis of MFS. Direct sequencing of the mutation in FBN1 may be used for diagnosis of MFS.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000301238300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry & Molecular BiologyOphthalmologySCI(E)PubMed10ARTICLE10-1181-861

Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice

AbstractExposure to ionizing radiation (IR) increases the production of reactive oxygen species (ROS) not only by the radiolysis of water but also through IR-induced perturbation of the cellular metabolism and disturbance of the balance of reduction/oxidation reactions. Our recent studies showed that the increased production of intracellular ROS induced by IR contributes to IR-induced late effects, particularly in the hematopoietic system, because inhibition of ROS production with an antioxidant after IR exposure can mitigate IR-induced long-term bone marrow (BM) injury. Metformin is a widely used drug for the treatment of type 2 diabetes. Metformin also has the ability to regulate cellular metabolism and ROS production by activating AMP-activated protein kinase. Therefore, we examined whether metformin can ameliorate IR-induced long-term BM injury in a total-body irradiation (TBI) mouse model. Our results showed that the administration of metformin significantly attenuated TBI-induced increases in ROS production and DNA damage and upregulation of NADPH oxidase 4 expression in BM hematopoietic stem cells (HSCs). These changes were associated with a significant increase in BM HSC frequency, a considerable improvement in in vitro and in vivo HSC function, and complete inhibition of upregulation of p16Ink4a in HSCs after TBI. These findings demonstrate that metformin can attenuate TBI-induced long-term BM injury at least in part by inhibiting the induction of chronic oxidative stress in HSCs and HSC senescence. Therefore, metformin has the potential to be used as a novel radioprotectant to ameliorate TBI-induced long-term BM injury

Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice

Senescent cells (SCs) accumulate with age and after genotoxic stress, such as total-body irradiation (TBI)1–6. Clearance of SCs in a progeroid mouse model using a transgenic approach delays several age-associated disorders7, suggesting that SCs play a causative role in certain age-related pathologies. Thus, a ‘senolytic’ pharmacological agent that can selectively kill SCs holds promise for rejuvenating tissue stem cells and extending health span. To test this idea, we screened a collection of compounds and identified ABT263 (a specific inhibitor of the anti-apoptotic proteins BCL-2 and BCL-xL) as a potent senolytic drug. We show that ABT263 selectively kills SCs in culture in a cell type– and species-independent manner by inducing apoptosis. Oral administration of ABT263 to either sublethally irradiated or normally aged mice effectively depleted SCs, including senescent bone marrow hematopoietic stem cells (HSCs) and senescent muscle stem cells (MuSCs). Notably, this depletion mitigated TBI-induced premature aging of the hematopoietic system and rejuvenated the aged HSCs and MuSCs in normally aged mice. Our results demonstrate that selective clearance of SCs by a pharmacological agent is beneficial in part through its rejuvenation of aged tissue stem cells. Thus, senolytic drugs may represent a new class of radiation mitigators and anti-aging agents

Serum Levels of Adipocyte Fatty Acid-Binding Protein Are Associated with the Severity of Coronary Artery Disease in Chinese Women

BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) has been described as a novel adipokine, playing an important role in the development of metabolic syndrome, type 2 diabetes and atherosclerosis. In this study, we investigated the relationship between serum levels of A-FABP and the presence and severity of coronary artery disease (CAD) in Chinese subjects. METHODOLOGY/PRINCIPAL FINDINGS: Circulating A-FABP level was determined by ELISA in 341 Chinese subjects (221 men, 120 women) who underwent coronary angiography. A-FABP levels in patients with CAD were significantly higher compared with non-CAD subjects (P = 0.029 in men; P = 0.031 in women). Serum A-FABP increased significantly in multi-vessel diseased patients than in non-CAD subjects (P = 0.011 in men, P = 0.004 in women), and showed an independent correlation with coronary atherosclerosis index (standardized β = 0.173, P = 0.025). In multiple logistic regression analysis, serum A-FABP was an independent risk factor for CAD in women (OR = 5.637, 95%CI: 1.299-24.457, P = 0.021). In addition, amino terminal pro-brain natriuretic peptide (NT-proBNP) was demonstrated to be positively and independently correlated with A-FABP (standardized β = 0.135, P = 0.027). CONCLUSIONS/SIGNIFICANCE: Serum A-FABP is closely associated with the presence and severity of CAD in Chinese women

A Research Review on Pricing Influencing Factors of Supply Chain Financial Services

Supply chain finance, as a kind of innovative financial products, has attracted extensive attention of the industry. In the context of capital operation, it is the most important to study the supply chain finance. Adopting content analysis method, this article combs the research on factors that affect supply chain financial service pricing from six dimensions of Supply Chain Finance: risk, return, regulation, guarantee, customer relationship and macro policy, expects to provide a theoretical basis for enterprises to set the loan price, and some guidance for financing enterprises to choose appropriate products

Synthesis of Benzothiophene-Fused Pyran Derivatives via Piperidine Promoted Domino Reaction

A new domino reaction between thioaurones and malononitrile has been reported. This reaction allows efficient access to benzothiophene-fused pyran derivatives in good yields under mild reaction conditions. The substrate scope is broad; a series of benzothiophene-fused pyran derivatives have been synthesized