Fully understanding the complicated interplays among various chemical species and organelles is greatly important to unravel the mystery of life. However, fluorescent probes capable of visualizing ...multiple targets discriminatively are severely deficient, which extremely limit the investigation on intracellular interplays among various species. Towards this end and in consideration of the unique advantages of aggregation-induced emission luminogens (AIEgens), here we rationally designed and presented a single AIEgen, named TVQE, bearing lipophilic, cationic and hydrolyzable moieties, and this AIEgen was capable of illuminating mitochondria and lipid droplets with red and blue emission, respectively. In addition, TVQE was successfully used for evaluating cell viability due to its distinct two-color emission changes tuned by esterase-mediated hydrolysis. Of particular importance is that TVQE can selectively differentiate live, early apoptotic, late apoptotic, and dead cells by confocal microscopy and quantify cell viability statistically by flow cytometry.
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Hyperhomocysteinemia is an independent risk factor for cardiovascular disease and accelerates atherosclerosis in apoE–/– mice. Despite the observations that homocysteine causes endoplasmic reticulum ...(ER) stress and programmed cell death (PCD) in cultured human vascular endothelial cells, the cellular factors responsible for this effect and their relevance to atherogenesis have not been completely elucidated. We report here that homocysteine induces the expression of T-cell death-associated gene 51 (TDAG51), a member of the pleckstrin homology-related domain family, in cultured human vascular endothelial cells. This effect was observed for other ER stress-inducing agents, including dithiothreitol and tunicamycin. TDAG51 expression was attenuated in homozygous A/A mutant eukaryotic translation initiation factor 2α mouse embryonic fibroblasts treated with homocysteine or tunicamycin, suggesting that ER stress-induced phosphorylation of eukaryotic translation initiation factor 2α is required for TDAG51 transcriptional activation. Transient overexpression of TDAG51 elicited significant changes in cell morphology, decreased cell adhesion, and promoted detachment-mediated PCD. In support of these in vitro findings, TDAG51 expression was increased and correlated with PCD in the atherosclerotic lesions from apoE–/– mice fed hyperhomocysteinemic diets, compared with mice fed a control diet. Collectively, these findings provide evidence that TDAG51 is induced by homocysteine, promotes detachment-mediated PCD, and contributes to the development of atherosclerosis observed in hyperhomocysteinemia.
Recent evidence suggests a role for aberrant ceramide levels in the pathogenesis of cancer and chemoresistance and indicates that manipulation of tumor ceramide levels may be a useful strategy in the ...fight against breast cancer. This study demonstrates that alterations in the degree and position of unsaturation of bonds in the sphingoid backbone of d-erythro-N-octanoyl-sphingosine (Cer) affect the antiproliferative ability of ceramide analogs in breast cancer cells. The most potent analog of Cer we tested is (2S,3R)-(4E,6E)-2-octanoylamidooctadecadiene-1,3-diol (4,6-diene-Cer), which contains an additional trans double bond at C(6)-C(7) of the sphingoid backbone. 4,6-Diene-Cer exhibited higher potency than Cer in tumor necrosis factor (TNF)-alpha-resistant (IC(50) of 11.3 versus 32.9 microM) and TNF-alpha-sensitive (IC(50) of 13.7 versus 37.7 microM) MCF-7 cells. 4,6-Diene-Cer was also more potent than Cer in inducing cell death in MDA-MB-231 and NCI/ADR-RES breast cancer cell lines (IC(50) of 3.7 versus 11.3 microM, and 24.1 versus 86.9 microM, respectively). 4,6-Diene-Cer caused a prolonged elevation of intracellular ceramide levels in MCF-7 cells, which may contribute to its enhanced cytotoxicity. Furthermore, treatment of MCF-7 cells with Cer or 4,6-diene-Cer resulted in induction of apoptosis by 8 h via the mitochondrial pathway, as demonstrated by release of cytochrome c, loss of membrane asymmetry (measured by Annexin V staining), and a decrease in the mitochondrial membrane potential. Importantly, both Cer and 4,6-diene-Cer displayed selectivity toward transformed breast cells over nontransformed breast epithelial cells. These data suggest that these and other novel ceramide analogs represent potential therapeutic agents in breast cancer treatment.
Tremella-like structured MoO
2 consisting of nanosheets was obtained
via a Fe
2O
3-assisted hydrothermal reduction of MoO
3 in ethylenediamine aqueous solution. The as-prepared product was ...characterized and tested with scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV) and capacity measurement as anode material for lithium ion batteries. This structured MoO
2 shows very high reversible capacity (>600
mA
h
g
−1), good rate capability and cycling performance, presenting potential application as anode material for lithium ion batteries with high rate capability and high capacity.
Falls from ladders: age matters more than height Con, Jorge, MD; Friese, Randall S., MD; Long, Dustin M., PhD ...
The Journal of surgical research,
10/2014, Letnik:
191, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract Background Falls from ladders account for a significant number of hospital visits. However, the epidemiology, injury pattern, and how age affects such falls are poorly described in the ...literature. Materials and methods Patients ≥18 y who suffered falls from ladders over a 5½-y period were identified in our trauma registry. Dividing patients into three age groups (18–45, 46–65, and >66 y), we compared demographic characteristics, clinical data, and outcomes including injury pattern and mortality. The odds ratios (ORs) were calculated with the group 18–45 y as reference; group means were compared with one-way analysis of variance. Results Of 27,155 trauma patients, 340 (1.3%) had suffered falls from ladders. The average age was 55 y, with a male predominance of 89.3%. Average fall height was 9.8 ft, and mean Injury Severity Score was 10.6. Increasing age was associated with a decrease in the mean fall height ( P < 0.001), an increase in the mean Injury Severity Score ( P < 0.05), and higher likelihood of admission (>66 y: OR, 5.3; confidence interval CI, 2.5–11.5). In univariate analysis, patients in the >66-y age group were more likely to sustain traumatic brain injuries (OR, 3.4; CI, 1.5–7.8) and truncal injuries (OR, 3.6; CI, 1.9–7.0) and less likely to sustain hand and/or forearm fractures (OR, 0.3; CI, 0.1–0.9). Conclusions Older people are particularly vulnerable after falling from ladders. Although they fell from lower heights, the elderly sustained different and more severe injury patterns. Ladder safety education should be particularly tailored at the elderly.
Some FeTPP−Cl/carbon electrocatalysts, heat-treated at temperatures up to 800 °C, have been studied with cyclic voltammetry, x-ray photoelectron spectroscopy, extended X-ray absorption fine ...structure, and in situ Mössbauer spectroscopy. It appears that the heat treatment induces considerable site heterogeneity in electronic terms, although structurally the Fe−N4 moiety seems persistent. The data indicate that only part of these Fe−N4 sites contributes to the activity for the electrochemical reduction of O2 but that they operate according to the well-known redox mechanism.
Sildenafil, an inhibitor of cGMP-specific phosphodiesterase 5 (PDE5), is currently undergoing evaluation as an oral therapy for penile erectile dysfunction. The aims of this study were to investigate ...the mechanism of action of sildenafil on the neurogenic relaxation of human corpus cavernosum (HCC) in vitro and to determine the activity of sildenafil against a full range of PDE isozymes.
Strips of HCC tissue were precontracted with phenylephrine. Relaxation responses resulting from electrical field stimulation (EFS) were then determined in the presence and absence of sildenafil. The effects of sildenafil on PDE1 to 5 prepared from human tissues and PDE6 from bovine retina were determined by measuring the conversion of (
3) H-cGMP or (
3) H-cAMP to their respective (
3) H-5′-mononucleotides.
Sildenafil (0.001 to 1 micro M) enhanced the EFS-induced, nitric oxide (NO) dependent, relaxation of HCC in a concentration-dependent manner to a maximum of 3 times the pretreatment level at 1 micro M sildenafil. Compared with zaprinast, an early PDE5 inhibitor, sildenafil was approximately 240-fold more potent, inhibiting PDE5 from HCC with a geometric mean IC
50 of 3.5 nM. For sildenafil, IC
50 values for inhibition of PDE1 to 4 were 80 to more than 8500 times greater than that for PDE5 and the IC
50 for PDE6 (33 nM) was approximately 9-fold greater.
The data support the proposal that enhancement of penile erection by sildenafil in patients with erectile dysfunction involves potentiation of the NO-stimulated cGMP signal mediating relaxation of cavernosal smooth muscle during sexual stimulation. Sildenafil is a potent inhibitor of PDE5 from HCC, with high selectivity for PDE5 relative to other PDE isozymes.
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