The association between vascular stiffening and blood pressure is likely bidirectional. The present study was designed to examine temporal relationships among vascular stiffness, blood pressure progression, and hypertension. The Asymptomatic Polyvascular Abnormalities Community study is a community-based, prospective, long-term follow-up observational study. The present investigation is based on the baseline examinations (2010)(2011) and the first follow-up measurements (2012)(2013) included in the study. A total of 4025 participants were followed for an average of 27 months. Of 2153 participants free of hypertension at the baseline examination, 432 (20.07%) had incident hypertension. The authors observed that brachial-ankle pulse wave velocity (baPWV) was an independent predictor of incident hypertension. baPWV during baseline examination was positively associated with higher systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure during the first follow-up examination. baPWV but not blood pressure during baseline examination was associated with baPWV during the first follow-up examination. This study not only provides evidence that baPWV is an independent predictor of blood pressure progression and incident hypertension, but also provides evidence that blood pressure is not associated with baPWV after adjusting for baseline baPWV. J Clin Hypertens (Greenwich). 2015;17:582-591. ª 2015 Wiley Periodicals, Inc.Arterial stiffness and blood pressure (BP), which increase with age, are associated with increased morbidity and mortality of cardiovascular diseases.1,2 It is traditionally believed that elevated BP may cause structural and functional alterations in the walls of the central elastic arteries and accelerated conduit artery stiffening.3,4 Conversely, conduit artery stiffening may increase pressure pulsatility and thereby may increase systolic BP (SBP). Temporal relationships between vascular stiffness and BP remain incompletely elucidated. Moreover, arterial stiffness is increasingly recognized as an important prognostic index and potential therapeutic target in patients with hypertension. 5,6 The 2013 guidelines for the management of arterial hypertension acknowledge the potential role of arterial stiffness measurement in clinical management. 7Several previous observational studies have revealed that aortic stiffness predicts progression to hypertension in normotensive individuals. [8][9][10][11][12][13][14][15] However, assessment of aortic stiffness using echocardiography is not the most suitable method since specialized equipment and expertise is required. Carotid-femoral pulse wave velocity (cf-PWV) is considered a "gold-standard" method for assessing central artery stiffness, but the technique is hindered by the intimate nature of femoral pulse acquisition and is not the most suitable method for mass examination of individuals to identify those with increased risk of hypertension. Brachial-ankle pulse wave velocity (baPWV) is an alternatively developed technique with...

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Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

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Background and aim Upregulation of prolyl isomerase-1 (Pin1) protein expression and activity was associated with the pathogenesis of diabetic vasculopathy through induction of endothelial oxidative stress and inflammation. Moreover, VDR agonist protects against high glucose-induced endothelial apoptosis through the inhibition of oxidative stress. We aimed to explore the effects of the VDR agonist on diabetes-associated endothelial dysfunction and the role of Pin1 in this process. Methods Streptozocin-induced diabetic mice were randomly treated with vehicle, VDR agonist (10 μg/kg/d, i.g., twice a week), or Pin1 inhibitor, Juglone (1 mg/kg/d, i.p., every other day), for eight weeks. In parallel, human umbilical vein endothelial cells (HUVECs) exposed to high-glucose condition were treated with 1,25-dihydroxyvitamin D3 and Juglone or vehicle for 72 hours. Organ chamber experiments were performed to assess endothelium-dependent relaxation to acetylcholine. Circulatory levels of Pin1, SOD, MDA, IL-1β, IL-6, and NO in diabetic mice, Pin1 protein expression and activity, subcellular distribution of p66Shc, and NF-κB p65 in high glucose-cultured HUVECs were determined. Results Both VDR agonist and Juglone significantly improved diabetes-associated endothelial dysfunction and reduced high glucose-induced endothelial apoptosis. Mechanistically, the circulatory levels of SOD and NO were increased compared with those of vehicle-treated diabetic mice. Additionally, Pin1 protein expression and activity, p66Shc mitochondrial translocation, and NF-κB p65 in high glucose-cultured HUVECs were also inhibited by VDR agonist and Juglone. Knockdown of VDR abolished the inhibitory effects of VDR agonist on high glucose-induced upregulation of Pin1 protein expression and activity. Conclusions VDR agonist prevents diabetic endothelial dysfunction through inhibition of Pin1-mediated mitochondrial oxidative stress and inflammation.