Sevoflurane, Propofol and Carvedilol Block Myocardial Protection by Limb Remote Ischemic Preconditioning

The effects of remote ischemic preconditioning (RIPC) in cardiac surgery have been inconsistent. We investigated whether anesthesia or beta-blockers interfere with RIPC cardioprotection. Fifty patients undergoing cardiac surgery were randomized to receive limb RIPC (four cycles of 5-min of upper arm cuff inflation/deflation) in the awake state (no-anesthesia; n = 17), or under sevoflurane (n = 17) or propofol (n = 16) anesthesia. In a separate crossover study, 11 healthy volunteers received either carvedilol or no medication prior to RIPC. Plasma dialysates were obtained and perfused through an isolated male Sprague⁻Dawley rat heart subjected to 30-min ischemia/60-min reperfusion, following which myocardial infarct (MI) size was determined. In the cardiac surgery study, pre-RIPC MI sizes were similar among the groups (39.7 ± 4.5% no-anesthesia, 38.9 ± 5.3% sevoflurane, and 38.6 ± 3.6% propofol). However, post-RIPC MI size was reduced in the no-anesthesia group (27.5 ± 8.0%; p < 0.001), but not in the anesthesia groups (35.7 ± 6.9% sevoflurane and 35.8 ± 5.8% propofol). In the healthy volunteer study, there was a reduction in MI size with RIPC in the no-carvedilol group (41.7 ± 4.3% to 30.6 ± 8.5%; p < 0.0001), but not in the carvedilol group (41.0 ± 4.0% to 39.6 ± 5.6%; p = 0.452). We found that the cardioprotective effects of limb RIPC were abolished under propofol or sevoflurane anesthesia and in the presence of carvedilol therapy

Interactions between Transmembrane Helices within Monomers of the Aquaporin AtPIP2;1 Play a Crucial Role in Tetramer Formation

Aquaporin (AQP) is a water channel protein found in various subcellular membranes of both prokaryotic and eukaryotic cells. The physiological functions of AQPs have been elucidated in many organisms. However, understanding their biogenesis remains elusive, particularly regarding how they assemble into tetramers. Here, we investigated the amino acid residues involved in the tetramer formation of the Arabidopsis plasma membrane AQP AtPIP2; 1 using extensive amino acid substitution mutagenesis. The mutant proteins V41A/E44A, F51A/L52A, F87A/I91A, F92A/I93A, V95A/Y96A, and H216A/L217A, harboring alanine substitutions in the transmembrane (TM) helices of AtPIP2; 1 polymerized into multiple oligomeric complexes with a variable number of subunits greater than four. Moreover, these mutant proteins failed to traffic to the plasma membrane, instead of accumulating in the endoplasmic reticulum(ER). Structure-based modeling revealed that these residues are largely involved in interactions between TM helices within monomers. These results suggest that inter-TM interactions occurring both within and between monomers play crucial roles in tetramer formation in the AtPIP2; 1 complex. Moreover, the assembly of AtPIP2; 1 tetramers is critical for their trafficking from the ER to the plasma membrane, as well as water permeability.1133Ysciescopu

Effects of delayed remote ischemic preconditioning on peri-operative myocardial injury in patients undergoing cardiac surgery - A randomized controlled trial

BACKGROUND: Remote ischemic preconditioning (RIPC) has two time windows for organ protection: acute and delayed. Previous studies have mainly focused on the acute time window to evaluate organ protection by RIPC. We evaluated myocardial protection by delayed RIPC in adult patients undergoing cardiac surgery. METHODS: A total of 160 adult patients undergoing cardiac surgery with cardiopulmonary bypass were randomized to receive either delayed RIPC (four cycles of 5 min of ischemia followed by 5 min of reperfusion by inflation to 200 mm Hg and deflation of a blood pressure cuff on the upper arm) or the control treatment 24–48 h before surgery. The primary endpoint was post-operative troponin I levels serially measured for 72 h. Secondary endpoints included post-operative serum creatinine levels, acute kidney injury, and composite complications. RESULTS: There were no significant differences in post-operative troponin I values. The incidence of acute kidney injury, defined by the Acute Kidney Injury Network staging system, was lower in the delayed RIPC group compared to the control group (30.0% vs. 47.5%; relative risk, 0.768; 95% confidence interval, 0.599–0.985; p = 0.023). Moreover, the occurrence of composite complications was lower in the delayed RIPC group compared with the control group (65.0% vs. 81.3%; relative risk, 0.536; 95% confidence interval, 0.311–0.924; p = 0.020). CONCLUSIONS: While RIPC did not provide cardioprotective effects in patients undergoing cardiac surgery, it appeared to reduce acute kidney injury, as well as the rate of composite complications

Proteomic profile of KSR1-regulated signalling in response to genotoxic agents in breast cancer

Kinase suppressor of Ras 1 (KSR1) has been implicated in tumorigenesis in multiple cancers, including skin, pancreatic and lung carcinomas. However, our recent study revealed a role of KSR1 as a tumour suppressor in breast cancer, the expression of which is potentially correlated with chemotherapy response. Here, we aimed to further elucidate the KSR1-regulated signalling in response to genotoxic agents in breast cancer. Stable isotope labelling by amino acids in cell culture (SILAC) coupled to high-resolution mass spectrometry (MS) was implemented to globally characterise cellular protein levels induced by KSR1 in the presence of doxorubicin or etoposide. The acquired proteomic signature was compared and GO-STRING analysis was subsequently performed to illustrate the activated functional signalling networks. Furthermore, the clinical associations of KSR1 with identified targets and their relevance in chemotherapy response were examined in breast cancer patients. We reveal a comprehensive repertoire of thousands of proteins identified in each dataset and compare the unique proteomic profiles as well as functional connections modulated by KSR1 after doxorubicin (Doxo-KSR1) or etoposide (Etop-KSR1) stimulus. From the up-regulated top hits, several proteins, including STAT1, ISG15 and TAP1 are also found to be positively associated with KSR1 expression in patient samples. Moreover, high KSR1 expression, as well as high abundance of these proteins, is correlated with better survival in breast cancer patients who underwent chemotherapy. In aggregate, our data exemplify a broad functional network conferred by KSR1 with genotoxic agents and highlight its implication in predicting chemotherapy response in breast cancer

ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro

<p>Abstract</p> <p>Background</p> <p>Dengue virus (DENV) and West Nile virus (WNV), close siblings of the <it>Flaviviridae </it>family, are the causative agents of Dengue hemorraghic shock or West Nile meningoencephalitis respectively. Vaccines against these two flaviviruses are currently unavailable. Interferon- Stimulated Gene 15 (<it>ISG15</it>), encoding an ubiquitin-like protein, is significantly induced by type I interferons or viral infections. Its roles in viral infections, however, vary with viruses, being either anti- or pro-viral. The exact roles of ISG15 in DENV and WNV infections remain unknown. In the current study, we evaluated the relevancies of ISG15 to DENV and WNV infection of a mouse macrophage cell line RAW264.7.</p> <p>Findings</p> <p>Quantitative PCR showed that mouse <it>Isg15 </it>was dramatically induced in DENV or WNV- infected RAW264.7 cells compared with non-infected cells. <it>Isg15 </it>and two other Jak-Stat related genes, <it>Socs1 </it>and <it>Socs3</it>, were silenced using siRNA mediated RNA interference. The intracellular DENV and WNV loads, as determined by quantitative PCR, were significantly higher in <it>Isg15 </it>silenced cells than control cells. The expression levels of interferon beta 1 (<it>Ifnb1</it>) were increased significantly in <it>Isg15</it>, <it>Socs1 </it>or <it>Socs3 </it>siRNA treated cells. Further investigation indicated that protein modification by ISG15, so called ISGylation, was significantly enhanced in DENV-infected cells compared to that in non-infected cells.</p> <p>Conclusions</p> <p>These findings suggest that ISG15 plays an anti-DENV/WNV function via protein ISGylation.</p

Nanoparticulate TiO2-promoted PtRu/C catalyst for methanol oxidation: TiO2 nanoparticles promoted PtRu/C catalyst for MOR

To improve the electrocatalytic properties of PtRu/C in methanol electrooxidation, nanoparticulate TiO2-promoted PtRu/C catalysts were prepared by directly mixing TiO2 nanoparticles with PtRu/C. Using cyclic voltammetry, it was found that the addition of 10 wt% TiO2 nanoparticles can effectively improve the electrocatalytic activity and stability of the catalyst during methanol electro-oxidation. The value of the apparent activation energy (Ea) for TiO2-PtRu/C was lower than that for pure PtRu/C at a potential range from 0.45 to 0.60 V. A synergistic effect between PtRu and TiO2 nanoparticles is likely to facilitate the removal of CO-like intermediates from the surface of PtRu catalyst and reduce the poisoning of the PtRu catalysts during methanol electrooxidation. Therefore, we conclude that the direct introduction of TiO2 nanoparticles into PtRu/ C catalysts offers an improved facile method to enhance the electrocatalytic performance of PtRu/C catalyst in methanol electrooxidation.Web of Scienc

An Antireflective Nanostructure Array Fabricated by Nanosilver Colloidal Lithography on a Silicon Substrate

An alternative method is presented for fabricating an antireflective nanostructure array using nanosilver colloidal lithography. Spin coating was used to produce the multilayered silver nanoparticles, which grew by self-assembly and were transformed into randomly distributed nanosilver islands through the thermodynamic action of dewetting and Oswald ripening. The average size and coverage rate of the islands increased with concentration in the range of 50–90 nm and 40–65%, respectively. The nanosilver islands were critically affected by concentration and spin speed. The effects of these two parameters were investigated, after etching and wet removal of nanosilver residues. The reflection nearly disappeared in the ultraviolet wavelength range and was 17% of the reflection of a bare silicon wafer in the visible range

Nutrition, Diabetes and Tuberculosis in the Epidemiological Transition

BACKGROUND: Diabetes prevalence and body mass index reflect the nutritional profile of populations but have opposing effects on tuberculosis risk. Interactions between diabetes and BMI could help or hinder TB control in growing, aging, urbanizing populations. METHODS AND FINDINGS: We compiled data describing temporal changes in BMI, diabetes prevalence and population age structure in rural and urban areas for men and women in countries with high (India) and low (Rep. Korea) TB burdens. Using published data on the risks of TB associated with these factors, we calculated expected changes in TB incidence between 1998 and 2008. In India, TB incidence cases would have increased (28% from 1.7 m to 2.1 m) faster than population size (22%) because of adverse effects of aging, urbanization, changing BMI and rising diabetes prevalence, generating an increase in TB incidence per capita of 5.5% in 10 years. In India, general nutritional improvements were offset by a fall in BMI among the majority of men who live in rural areas. The growing prevalence of diabetes in India increased the annual number of TB cases in people with diabetes by 46% between 1998 and 2008. In Korea, by contrast, the number of TB cases increased more slowly (6.1% from 40,200 to 42,800) than population size (14%) because of positive effects of urbanization, increasing BMI and falling diabetes prevalence. Consequently, TB incidence per capita fell by 7.8% in 10 years. Rapid population aging was the most significant adverse effect in Korea. CONCLUSIONS: Nutritional and demographic changes had stronger adverse effects on TB in high-incidence India than in lower-incidence Korea. The unfavourable effects in both countries can be overcome by early drug treatment but, if left unchecked, could lead to an accelerating rise in TB incidence. The prevention and management of risk factors for TB would reinforce TB control by chemotherapy