Abstract-Mutations in the bone morphogenetic protein type II receptor gene (BMPR2) are the major genetic cause of familial pulmonary arterial hypertension (FPAH). Although smooth muscle cell proliferation contributes to the vascular remodeling observed in PAH, the role of BMPs in this process and the impact of BMPR2 mutation remains unclear. Studies involving normal human pulmonary artery smooth muscle cells (PASMCs) suggest site-specific responses to BMPs. Thus, BMP-4 inhibited proliferation of PASMCs isolated from proximal pulmonary arteries, but stimulated proliferation of PASMCs from peripheral arteries, and conferred protection from apoptosis. These differences were not caused by differential activation of BMP signaling pathways because exogenous BMP-4 led to phosphorylation of Smad1, p38 MAPK , and ERK1/2 in both cell types. However, the proproliferative effect of BMP-4 on peripheral PASMCs was found to be p38 MAPK /ERK-dependent. Conversely, overexpression of dominant-negative Smad1 converted the response to BMP-4 in proximal PASMCs from inhibitory to proliferative. Furthermore, we confirmed that proximal PASMCs harboring kinase domain mutations in BMPR2 are deficient in Smad signaling and are unresponsive to the growth suppressive effect of BMP-4. Moreover, we show that the pulmonary vasculature of patients with familial and idiopathic PAH are deficient in the activated form of Smad1. We conclude that defective Smad signaling and unopposed p38 MAPK /ERK signaling, as a consequence of mutation in BMPR2, underlie the abnormal vascular cell proliferation observed in familial PAH. Key Words: vascular remodeling Ⅲ pulmonary hypertension Ⅲ transforming growth factor-␤ Ⅲ smooth muscle cells Ⅲ cell signaling P rimary, or idiopathic, pulmonary arterial hypertension (IPAH) is a rare disorder that is progressive and often fatal, leading to death within a median of 3 years from right ventricular failure without treatment. 1 The disease is characterized by vascular cell proliferation and obliteration of small pulmonary arteries by smooth muscle cells and myofibroblasts. 2 In addition, plexiform lesions comprising endothelial cells and myofibroblasts are found in Ϸ50% of cases. 3 Genetic studies have revealed heterozygous mutations in the BMPR2 gene encoding the type II bone morphogenetic protein receptor (BMPR-II), a member of the TGF-␤ superfamily of receptors, 4,5 underlying the familial form of the disease (FPAH). Subsequently, BMPR2 mutations were found in Ϸ25% of apparently sporadic cases of IPAH, many of which are examples of familial transmission with low disease gene penetrance. 6,7 Although these genetic studies point toward a critical role for the TGF-␤ superfamily in the regulation of pulmonary vascular cell growth and differentiation, the precise molecular mechanisms leading to disease pathogenesis remain to be elucidated.Signaling by BMP receptors involves heterodimerization of 2 transmembrane serine/threonine kinases: the constitutively active type II receptor, BMPR-II, and a corresponding type I re...

Contamination with pathogenic and infectious viruses severely threatens human health and animal husbandry. Current methods for disinfection have different disadvantages, such as inconvenience and contamination of disinfection by-products (e.g., chlorine disinfection). In this study, atmospheric surface plasma in argon mixed with air and plasma-activated water was found to efficiently inactivate bacteriophages, and plasma-activated water still had strong antiviral activity after prolonged storage. Furthermore, it was shown that bacteriophage inactivation was associated with damage to nucleic acids and proteins by singlet oxygen. An understanding of the biological effects of plasma-based treatment is useful to inform the development of plasma into a novel disinfecting strategy with convenience and no by-product.

No abstract

Reactive oxygen and nitrogen species produced by cold atmospheric plasma (CAP) are considered to be the most important species for biomedical applications, including cancer treatment. However, it is not known which species exert the greatest biological effects, and the nature of their interactions with tumor cells remains ill-defined. These questions were addressed in the present study by exposing human mesenchymal stromal and LP-1 cells to reactive oxygen and nitrogen species produced by CAP and evaluating cell viability. Superoxide anion (O2 −) and hydrogen peroxide (H2O2) were the two major species present in plasma, but their respective concentrations were not sufficient to cause cell death when used in isolation; however, in the presence of iron, both species enhanced the cell death-inducing effects of plasma. We propose that iron containing proteins in cells catalyze O2 − and H2O2 into the highly reactive OH radical that can induce cell death. The results demonstrate how reactive species are transferred to liquid and converted into the OH radical to mediate cytotoxicity and provide mechanistic insight into the molecular mechanisms underlying tumor cell death by plasma treatment.

No abstract

It is well established that atmospheric pressure glow discharges are capable of bacterial inactivation. Much less known is their ability to destruct infectious proteins, even though surgical instruments are often contaminated by both bacteria and proteinaceous matters. In this letter, the authors present a study of protein destruction using a low-temperature atmospheric dielectric-barrier discharge jet. Clear evidences of protein removal are presented with data of several complimentary experiments using scanning electron microscopy, electron dispersive x-ray analysis, electrophoresis, laser-induced fluorescence microscopy, and protein reduction kinetics. Considerable degradation is observed of protein fragments that remain on their substrate surface after plasma treatment.

No abstract

A novel method is developed to fabricate the polypyrrole (PPy) and graphene thin films on electrodes by electrochemical polymerization of pyrrole with graphene oxide (GO) as a dopant, followed by electrochemical reduction of GO in the composite film. The composite of PPy and electrochemically reduced graphene oxide (eRGO)-modified electrode is highly sensitive and selective toward the detection of dopamine (DA) in the presence of high concentrations of ascorbic acid (AA) and uric acid (UA). The sensing performance of the PPy/eRGO-modified electrode is investigated by differential pulse voltammetry (DPV), revealing a linear range of 0.1-150 μM with a detection limit of 23 nM (S/N = 3). The practical application of the PPy/eRGO-modified electrode is successfully demonstrated for DA determination in human blood serum.