Nogo-B regulates migration and contraction of airway smooth muscle cells by decreasing ARPC 2/3 and increasing MYL-9 expression

<p>Abstract</p> <p>Background</p> <p>Abnormal proliferation, apoptosis, migration and contraction of airway smooth muscle (ASM) cells in airway remodeling in asthma are basically excessive repair responses to a network of inflammatory mediators such as PDGF, but the mechanisms of such responses remain unclear. Nogo-B, a member of the reticulum family 4(RTN4), is known to play a key role in arteriogenesis and tissue repair. Further studies are needed to elucidate the role of Nogo-B in airway smooth muscle abnormalities.</p> <p>Methods</p> <p>A mouse model of chronic asthma was established by repeated OVA inhalation and subjected to Nogo-B expression analysis using immunohistochemistry and Western Blotting. Then, primary human bronchial smooth muscle cells (HBSMCs) were cultured <it>in vitro </it>and a siRNA interference was performed to knockdown the expression of Nogo-B in the cells. The effects of Nogo-B inhibition on PDGF-induced HBSMCs proliferation, migration and contraction were evaluated. Finally, a proteomic analysis was conducted to unveil the underlying mechanisms responsible for the function of Nogo-B.</p> <p>Results</p> <p>Total Nogo-B expression was approximately 3.08-fold lower in chronic asthmatic mice compared to naïve mice, which was obvious in the smooth muscle layer of the airways. Interference of Nogo-B expression by siRNA resulted nearly 96% reduction in mRNA in cultured HBSMCs. In addition, knockdown of Nogo-B using specific siRNA significantly decreased PDGF-induced migration of HBSMCs by 2.3-fold, and increased the cellular contraction by 16% compared to negative controls, but had limited effects on PDGF-induced proliferation. Furthermore, using proteomic analysis, we demonstrate that the expression of actin related protein 2/3 complex subunit 5 (ARPC 2/3) decreased and, myosin regulatory light chain 9 isoform a (MYL-9) increased after Nogo-B knockdown.</p> <p>Conclusions</p> <p>These data define a novel role for Nogo-B in airway remodeling in chronic asthma. Endogenous Nogo-B, which may exert its effects through ARPC 2/3 and MYL-9, is necessary for the migration and contraction of airway smooth muscle cells.</p

Mean sojourn time, overdiagnosis, and reduction in advanced stage prostate cancer due to screening with PSA: implications of sojourn time on screening

This study aimed to assess the mean sojourn time (MST) of prostate cancer, to estimate the probability of overdiagnosis, and to predict the potential reduction in advanced stage disease due to screening with PSA. The MST of prostate cancer was derived from detection rates at PSA prevalence testing in 43 842 men, aged 50–69 years, as part of the ProtecT study, from the incidence of non-screen-detected cases obtained from the English population-based cancer registry database, and from PSA sensitivity obtained from the medical literature. The relative reduction in advanced stage disease was derived from the expected and observed incidences of advanced stage prostate cancer. The age-specific MST for men aged 50–59 and 60–69 years were 11.3 and 12.6 years, respectively. Overdiagnosis estimates increased with age; 10–31% of the PSA-detected cases were estimated to be overdiagnosed. An interscreening interval of 2 years was predicted to result in 37 and 63% reduction in advanced stage disease in men 65–69 and 50–54 years, respectively. If the overdiagnosed cases were excluded, the estimated reductions were 9 and 54%, respectively. Thus, the benefit of screening in reducing advanced stage disease is limited by overdiagnosis, which is greater in older men

Molecular origin of enhanced proton conductivity in anhydrous ionic systems

YesIonic systems with enhanced proton conductivity are widely viewed as promising electrolytes in fuel cells and batteries. Nevertheless, a major challenge toward their commercial applications is determination of the factors controlling the fast proton hopping in anhydrous conditions. To address this issue, we have studied novel proton-conducting materials formed via a chemical reaction of lidocaine base with a series of acids characterized by a various number of proton-active sites. From ambient and high pressure experimental data, we have found that there are fundamental differences in the conducting properties of the examined salts. On the other hand, DFT calculations revealed that the internal proton hopping within the cation structure strongly affects the pathways of mobility of the charge carrier. These findings offer a fresh look on the Grotthuss-type mechanism in protic ionic glasses as well as provide new ideas for the design of anhydrous materials with exceptionally high proton conductivity

The prevalence of autosomal dominant polycystic kidney disease (ADPKD): A meta-analysis of European literature and prevalence evaluation in the Italian province of Modena suggest that ADPKD is a rare and underdiagnosed condition

ADPKD is erroneously perceived as a not rare condition, which is mainly due to the repeated citation of a mistaken interpretation of old epidemiological data, as reported in the Dalgaard's work (1957). Even if ADPKD is not a common condition, the correct prevalence of ADPKD in the general population is uncertain, with a wide range of estimations reported by different authors. In this work, we have performed a meta-analysis of available epidemiological data in the European literature. Furthermore we collected the diagnosis and clinical data of ADPKD in a province in the north of Italy (Modena). We describe the point and predicted prevalence of ADPKD, as well as the main clinical characteristics of ADPKD in this region

Genotypes of autosomal dominant polycystic kidney disease in Japanese

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders. The prevalence of the ADPKD genotype in the Caucasian and Latin populations has been reported. Here, we used linkage analysis to demonstrate the prevalence of the genotype and the correlation between phenotypes and genotypes among 21 Japanese ADPKD families consisting of 96 individuals and including 57 affected members. Six polymorphic markers, each linked to either the polycystic kidney disease 1 (PKD1) or polycystic kidney disease 2 (PKD2) gene, were used for polymerase chain reaction analysis. Seventeen families (81%) showed linkage to PKD1, two families (10%) showed linkage to PKD2, and two families did not show linkage to either PKD1 or PKD2. One of the PKD1-linked families was indicated to have different mutations of PKD1 gene in the same family. PKD2-linked families did not have milder symptoms than PKD1-linked families

2,2 &apos;-Bis(1,3,4-thiadiazole)-Based pi-Conjugated Copolymers for Organic Photovoltaics with Exceeding 8% and Its Molecular Weight Dependence of Device Performance

A series of novel ��-conjugated copolymers based on 2,2��-bis(1,3,4-thiadiazole) (BTDz) have been developed. Among them, the BTDz-based donor-acceptor alternating copolymer with the (E)-1,2-di(3-(2-ethylhexyl)thiophene)vinylene donor unit (PBTDzTV) exhibited a high solubility and high crystallinity. PBTDzTVs favorably self-assembled, forming face-on and edge-on multibilayer structures in thin nanoscale films. The relative volume fractions of these structures varied depending on the polymer��s molecular weight. The higher molecular weight polymer formed a higher volume fraction of the face-on structure; in particular, the polymer with a 26.6 kDa of number-average molecular weight made only the face-on structure. The device performance was improved as the polymer molecular weight and the volume fraction of the face-on structure increased. The bulk-heterojunction photovoltaic device based on PBTDzTV:PC71BM demonstrated the high power conversion efficiency (PCE) of 8.04% when the device was fabricated with the highest molecular weight polymer having the face-on structure. ? 2017 American Chemical Society.1110sciescopu

Synthesis and Characterization of Polythiophenes Bearing Aromatic Groups at the 3-Position

Regioregular poly(3-(4&apos;-(3 &apos;&apos;,7 &apos;&apos;-dimethyloctoxy)phenyl)thiophene) (P3PhT) and poly(3-(4&apos;-(3 &apos;&apos;,7 &apos;&apos;-dimethyloctoxy)-3&apos;-pyridinyl)thiophene) (P3PyT) were successfully prepared with reasonably high molecular weights and low polydispersity indices by the Grignard metathesis (GRIM) polymerization. These polymers were found to be thermally stable up to 360-390 degrees C, depending on the phenyl or pyridinyl linker in the bristle. Both polymer films revealed a molecularly multilayer structure (i.e., lamellar structure) whose layers stacked normal to the film plane; each lamella consists of two sublayers, namely ordered and amorphous layers. The amorphous sublayer was composed of a bilayer formed from the bristles. The ordered sublayer in P3PhT consisted of laterally stacked 3-phenylthiophene backbone chains, whereas that of P3PyT consisted of thiophene backbone chains without the pyridinyl linker. These ordered sublayer formations led a longer pi-conjugation length. The enhanced pi-conjugation lengths were reflected in their optical and electronic properties, showing that both P3PhT and P3PyT exhibited a lower highest occupied molecular orbital (HOMO) level and lower energy band gap compared to those of poly(3-hexylthiophene) (P3HT). Overall, the structure and properties of P3PhT and P3PyT make them promising materials for advanced polymer solar cells having an excellent performance.X111720sciescopu