AGE-BSA down-regulates endothelial connexin43 gap junctions

<p>Abstract</p> <p>Background</p> <p>Advanced glycation end products generated in the circulation of diabetic patients were reported to affect the function of vascular wall. We examined the effects of advanced glycation end products-bovine serum albumin (AGE-BSA) on endothelial connexin43 (Cx43) expression and gap-junction communication.</p> <p>Results</p> <p>In human aortic endothelial cells (HAEC) treated with a series concentrations of AGE-BSA (0-500 μg/ml) for 24 and 48 hours, Cx43 transcript and Cx43 protein were reduced in a dose dependent manner. In addition, gap-junction communication was reduced. To clarify the mechanisms underlying the down-regulation, MAPKs pathways in HAEC were examined. Both a MEK1 inhibitor (PD98059) and a p38 MAPK inhibitor (SB203580) significantly reversed the reductions of Cx43 mRNA and protein induced by AGE-BSA. Consistently, phosphorylation of ERK and p38 MAPK was enhanced in response to exposure to AGE-BSA. However, all reversions of down-regulated Cx43 by inhibitors did not restore the functional gap-junction communication.</p> <p>Conclusions</p> <p>AGE-BSA down-regulated Cx43 expression in HAEC, mainly through reduced Cx43 transcription, and the process involved activation of ERK and p38 MAPK.</p

The potential application of ultra-nanocrystalline diamond films for heavy ion irradiation detection

[[abstract]]The potential of utilizing the ultra-nanocrystalline (UNCD) films for detecting the Au-ion irradiation was investigated. When the fluence for Au-ion irradiation is lower than the critical value (fc = 5.0 × 1012 ions/cm2) the turn-on field for electron field emission (EFE) process of the UNCD films decreased systematically with the increase in fluence that is correlated with the increase in sp2-bonded phase (π*-band in EELS) due to the Au-ion irradiation. The EFE properties changed irregularly, when the fluence for Au-ion irradiation exceeds this critical value. The transmission electron microscopic microstructural examinations, in conjunction with EELS spectroscopic studies, reveal that the structural change preferentially occurred in the diamond-to-Si interface for the samples experienced over critical fluence of Au-ion irradiation, viz. the crystalline SiC phase was induced in the interfacial region and the thickness of the interface decreased. These observations implied that the UNCD films could be used as irradiation detectors when the fluence for Au-ion irradiation does not exceed such a critical value.[[incitationindex]]SCI[[booktype]]電子

Dub3 Inhibition Suppresses Breast Cancer Invasion and Metastasis by Promoting Snail1 Degradation

Snail1, a key transcription factor of epithelial–mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitroand in vivo. Our study reveals a critical Dub3–Snail1 signalling axis in EMT and metastasis, and provides an effective therapeutic approach against breast cancer

Psoas Abscess Caused by Non-Typhoid Salmonella in a Patient with Severe Aplastic Anemia

The clinical spectrum of infections caused by non-typhoid Salmonella spp. includes gastroenteritis, enteric fever, bacteremia, and extraintestinal localized complications, especially in immunocompromised hosts. Here we report a patient with severe aplastic anemia developing left iliopsoas abscess caused by non-typhoid Salmonella (NTS), which was successfully treated by prolonged antibiotic treatment and repeated debridement. Our data indicate that aplastic anemia is a risk factor for infection caused by NTS

Deep Chandra X-ray Imaging of a Nearby Radio Galaxy 4C+29.30: X-ray/Radio Connection

We report results from our deep Chandra X-ray observations of a nearby radio galaxy, 4C+29.30 (z=0.0647). The Chandra image resolves structures on sub-arcsec to arcsec scales, revealing complex X-ray morphology and detecting the main radio features: the nucleus, a jet, hotspots, and lobes. The nucleus is absorbed (N(H)=3.95 (+0.27/-0.33)x10^23 atoms/cm^2) with an unabsorbed luminosity of L(2-10 keV) ~ (5.08 +/-0.52) 10^43 erg/s characteristic of Type 2 AGN. Regions of soft (<2 keV) X-ray emission that trace the hot interstellar medium (ISM) are correlated with radio structures along the main radio axis indicating a strong relation between the two. The X-ray emission beyond the radio source correlates with the morphology of optical line-emitting regions. We measured the ISM temperature in several regions across the galaxy to be kT ~ 0.5 with slightly higher temperatures (of a few keV) in the center and in the vicinity of the radio hotspots. Assuming these regions were heated by weak shocks driven by the expanding radio source, we estimated the corresponding Mach number of 1.6 in the southern regions. The thermal pressure of the X-ray emitting gas in the outermost regions suggest the hot ISM is slightly under-pressured with respect to the cold optical-line emitting gas and radio-emitting plasma, which both seem to be in a rough pressure equilibrium. We conclude that 4C+29.30 displays a complex view of interactions between the jet-driven radio outflow and host galaxy environment, signaling feedback processes closely associated with the central active nucleus.Comment: ApJ in pres

Spermine Synthase and MYC Cooperate to Maintain Colorectal Cancer Cell Survival by Repressing Bim Expression

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis and causes tumor regression, but these effects are profoundly attenuated by silencing Bim. These findings uncover a key survival signal in CRC through convergent repression of Bim expression by distinct SMS- and MYC-mediated signaling pathways. Thus, combined inhibition of SMS and MYC signaling may be an effective therapy for CRC

Plasma C-Reactive Protein and Endothelin-1 Level in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and associated with a worse survival and increased risk of hospitalization for exacerbation of COPD. However, little information exists regarding the potential role of systemic inflammation in pulmonary hypertension of COPD. The purpose of the present study was to investigate the degree of C-reactive protein (CRP) and endothelin-1 (ET-1) levels in COPD patient with and without pulmonary hypertension. The levels of CRP and ET-1 were investigated in 58 COPD patient with pulmonary hypertension and 50 patients without pulmonary hypertension. Pulmonary hypertension was defined as a systolic pulmonary artery pressure (Ppa) ≥35 mmHg assessed by Doppler echocardiography. Plasma CRP and ET-1 levels were significantly higher in patients with pulmonary hypertension than in patients without hypertension. There were significant positive correlations between the plasma ET-1 level and CRP level in the whole study groups. For COPD patients, systolic Ppa correlated significantly with plasma CRP levels and plasma ET-1 levels. These findings support a possibility that CRP and ET-1 correlate to pulmonary hypertension in COPD patients

Brain Cytosolic Phospholipase A2α Mediates Angiotensin II-Induced Hypertension and Reactive Oxygen Species Production in Male Mice

Abstract BACKGROUND Recently, we reported that angiotensin II (Ang II)-induced hypertension is mediated by group IV cytosolic phospholipase A2α (cPLA2α) via production of prohypertensive eicosanoids. Since Ang II increases blood pressure (BP) via its action in the subfornical organ (SFO), it led us to investigate the expression and possible contribution of cPLA2α to oxidative stress and development of hypertension in this brain area. METHODS Adenovirus (Ad)-green fluorescence protein (GFP) cPLA2α short hairpin (sh) RNA (Ad-cPLA2α shRNA) and its control Ad-scrambled shRNA (Ad-Scr shRNA) or Ad-enhanced cyan fluorescence protein cPLA2α DNA (Ad-cPLA2α DNA) and its control Ad-GFP DNA were transduced into SFO of cPLA2α+/+ and cPLA2α−/− male mice, respectively. Ang II (700 ng/kg/min) was infused for 14 days in these mice, and BP was measured by tail-cuff and radio telemetry. cPLA2 activity, reactive oxygen species production, and endoplasmic reticulum stress were measured in the SFO. RESULTS Transduction of SFO with Ad-cPLA2α shRNA, but not Ad-Scr shRNA in cPLA2α+/+ mice, minimized expression of cPLA2α, Ang II-induced cPLA2α activity and oxidative stress in the SFO, BP, and cardiac and renal fibrosis. In contrast, Ad-cPLA2α DNA, but not its control Ad-GFP DNA in cPLA2α−/− mice, restored the expression of cPLA2α, and Ang II-induced increase in cPLA2 activity and oxidative stress in the SFO, BP, cardiac, and renal fibrosis. CONCLUSIONS These data suggest that cPLA2α in the SFO is crucial in mediating Ang II-induced hypertension and associated pathogenesis. Therefore, development of selective cPLA2α inhibitors could be useful in treating hypertension and its pathogenesis