Excess Postexercise Oxygen Consumption and Interval Training

The effect of exercise intensity on excess postexercise oxygen consumption (EPOC) was determined in18 to 30 year old apparently healthy individuals. Subjects participated in 3 different exercise sessions; aerobic exercise, interval exercise (IE) and high intensity interval exercise (HIIE), on separate days. EPOC was measured one hour after each exercise while subjects were in supine position. ANOVA with repeated measurements was used to assess differences. The mean values (± SEM) for EPOC of aerobic exercise, IE and HIIE were 2.106(± 0.219), 2.846 (± 0.309) and 4.969 (± 0.522) l·hour -1. There was no significant difference (p \u3c 0.05) between mean EPOC of aerobic exercise and IE, however, a significant difference (p \u3c 0.05) was found in mean EPOC of HIIE when it was compared with both aerobic exercise and IE. These data suggest that exercise intensity has a significant effect on EPOC

Bisphenol A alters the function and expression of BK channels in vascular smooth muscle through membrane and nuclear signals

Bisphenol A (BPA) exposure has recently become a public health concern, and the safety of the utilization of BPA has attracted the attention of the scientific community, politicians, and the general population. Although BPA is banned from baby products in a few countries because infants and young children are particularly susceptible to endocrine disruption, recent studies have consistently indicated the association between urinary BPA concentration and cardiovascular diseases in adults. Therefore, adult exposure to this xenoestrogen is becoming a healthcare issue that cannot be ignored. We selected large conductance Ca2+/voltage sensitive potassium (BK) channels as one of the target proteins for BPA effects because the function and expression of BK channels are regulated by estrogen. Additionally, BK channels play an important role in vascular function and changes in BK expression are associated with disease. We hypothesized that BPA would differently affect BK channel function and expression via separate non-genomic and genomic mechanisms. The goals of our studies were 1) to characterize a novel, membrane-permeable, and economical antagonist called penitrem A to facilitate the study of BK channels, 2) to determine the mechanisms by which BPA increases BK channel activity and, 3) to determine the mechanisms by which BPA reduces vascular BK channel expression.;Current from patches of HEK 293 cells transfected with hSlo alpha or alpha + beta1 were blocked \u3e95% by penitrem A (IC50 6.4 vs. 64.4 nM; p\u3c0.05). Further, penitrem A inhibited BK channels in inside-out and cell-attached patches, whereas iberiotoxin could not. Inhibitory effects of penitrem A on whole-cell K+ currents were equivalent to iberiotoxin in canine coronary smooth muscle cells. Penitrem A enhanced sensitivity to K+-induced contraction in canine coronary arteries by 23 +/- 5% (p\u3c0.05) and increased the blood pressure response to phenylephrine in anesthetized mice by 36 +/- 11% (p\u3c0.05).;In cultured canine coronary artery smooth muscle cells (CASMC), acute BPA (10 microM) exposure increased BK channel currents 179 +/- 8% ( p\u3c0.05). Inside out recordings from native canine CASMCs showed that acute BPA increased BK channel open probability (Po) from 0.11 +/- 0.03 to 0.47 +/- 0.09 at +40 mV (p\u3c0.05). HEK cells transfected with BK alpha subunits alone were insensitive to acute BPA (currents at +100 mV were 101 +/- 13% of control) while acute BPA increased BK channel currents by 53 +/- 12% (p\u3c0.05) when cells were transfected with alpha and beta1 subunits. Similarly, single channel recordings indicated NPo was 123 +/- 20% of control in the BK alpha subunits alone with BPA, however, acute BPA increased NPo 201 +/- 41% in patches from cells expressing BK alpha and beta1 subunits. Thus, BK beta1 subunits facilitated BPA-induced BK channel activation and the effects of BPA were non-genomic, as these effects were observed in cell-free patches.;In contrast to the acute effects of BPA on BK channel activity, 48-72 hrs of BPA (10 microM) exposure decreased BK channel expression in A7r5 cells and cultured rat aorta. Western blot data indicated that BK alpha subunit protein content was 33 +/- 8% of control in BPA-treated aorta (p\u3c0.05). Patch clamp recording showed that whole cell current densities at +100 mV were 57 +/- 7% lower in aortic SMC treated with 10 microM BPA (p\u3c0.05) while whole cell current densities from aortic SMC treated with BPA + ICI 182780 (100 nM; an estrogen receptor blocker) were not different (101 +/- 14% of control). Penitrem A-sensitive current densities at 100 mV were 53.9 +/- 14.8, 12.0 +/- 3.0, and 48.4 +/- 10.1 pA/pF in DMSO, BPA and BPA + ICI 182780, respectively (p\u3c0.05). Thus, chronic BPA exposure decreased BK channel expression by estrogen receptor mediated signaling.;Our data indicate: 1) penitrem A is an economical alternative to iberiotoxin for BK channel analysis; 2) acute BPA exposure activates BK channel activity and BK beta1 subunits play a role in BPA induced BK channel activation; 3) chronic BPA exposure decreases vascular BK channel expression via estrogen receptor-dependent mechanisms. Although acute BPA exposure activates the BK channel through a non-genomic mechanism that could be beneficial for heart due to coronary dilation, longer BPA exposure decreases the number of functional BK channels through a genomic mechanism that could be detrimental to the heart. Thus, the overall effect of BPA exposure on vascular function may be harmful due to disruption of BK channel-mediated vascular regulation. Taken together, these results indicated BPA induced altered BK channel function and expression may be one of the mechanisms for the association between BPA exposure levels and cardiovascular diseases seen in epidemiological studies

Aging influences multiple indices of oxidative stress in the heart of the Fischer 344/NNia x Brown Norway/BiNia rat

Here we report the influence of aging on multiple markers of oxidativenitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36- month) Fischer 344/NNiaHSd X Brown Norway/BiNia (F344/NXBN) rats. Compared to 6 month old rat hearts, indices of oxidative (superoxide anion (–O2 ·), 4-hyrdoxy-2- nonenal (4-HNE)) and nitrosative (protein nitrotyrosylation) stress were 34.1 ± 28.1%, 186 ± 28.1% and 94 ± 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r\u3e0.669; r\u3e0.710 and p\u3c0.01, respectively). Regression analysis showed that increases in cardiac oxidative-nitrosative stress with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in transcriptional (NF-κB) activities, signaling (mitogen activated protein kinases along with Src), apoptotic ( Bcl-2, Traf-2), and cellular stress (HSPs). These results suggest that the aging F344/NXBN heart may be highly suited for unraveling the molecular events that lead to age-associated alterations in cardiac oxidative stress

Local conformation and intermolecular interaction of rigid ring polymers are not always the same as the linear analogue: Cyclic amylose tris(phenylcarbamate) in θ solvents

Asano N., Kitamura S., Terao K.. Local conformation and intermolecular interaction of rigid ring polymers are not always the same as the linear analogue: Cyclic amylose tris(phenylcarbamate) in θ solvents. Journal of Physical Chemistry B, 117(32), 9576-9583, July 23, 2013. Copyright © 2013, American Chemical Society. https://doi.org/10.1021/jp406607w

Rigid cyclic polymer in solution: Cycloamylose tris(phenylcarbamate) in 1,4-dioxane and 2-ethoxyethanol

Terao K., Asano N., Kitamura S., et al. Rigid cyclic polymer in solution: Cycloamylose tris(phenylcarbamate) in 1,4-dioxane and 2-ethoxyethanol. ACS Macro Letters, 1(11), 1291-1294, October 18, 2012. Copyright © 2012, American Chemical Society. https://doi.org/10.1021/mz3004506

Silenced Expression of NFKBIA in Lung Adenocarcinoma Patients with a Never-smoking History

Nuclear factor of κ-light polypeptide gene enhancer in B cells inhibitor α (NFKBIA), which is a tumor suppressor gene, was found to be silenced in lung adenocarcinomas. We examined NFKBIA expression, mutations in the EGFR and K-ras genes, and EML4-ALK fusion in 101 resected lung adenocarcinoma samples from never-smokers. NFKBIA expression was evaluated using immunohistochemistry. NFKBIA expression was negative in 16 of the 101 samples (15.8%). EGFR and K-ras mutations and EML4-ALK fusion were detected in 61 (60.5%), 1 (1.0%), and 2 (2.0%) of the 101 samples, respectively, in a completely mutually exclusive manner. Negative NFKBIA expression was observed significantly more frequently among the tumors with none of the three genetic alterations compared to those with such alterations (p＝0.009). In addition, negative NFKBIA expression was significantly more frequent among the EGFR-wild type samples compared to the EGFR-mutant samples (p＝0.013). In conclusion, NFKBIA expression was silenced in adenocarcinomas without EGFR/K-ras mutations or EML4-ALK fusion, suggesting that the silencing of NFKBIA may play an important role in the carcinogenesis of adenocarcinomas independent of EGFR/K-ras mutations or EML4-ALK fusion

Cerium oxide nanoparticles attenuate acute kidney injury induced by intra-abdominal infection in Sprague-Dawley rats

Background Intra-abdominal infection or peritonitis is a cause for great concern due to high mortality rates. The prognosis of severe intra-abdominal infection is significantly diminished in the presence of acute kidney injury (AKI) which is often characterized by renal tubular cell death that can lead to renal failure. The purpose of the current study is to examine the therapeutic efficacy of cerium oxide (CeO2) nanoparticles for the treatment of peritonitis-induced AKI by polymicrobial insult. Results A one-time administration of CeO2 nanoparticles (0.5 mg/kg) in the absence of antibiotics or other supportive care, attenuated peritonitis-induced tubular dilatation and the loss of brush border in male Sprague–Dawley rats. These improvements in renal structure were accompanied by decreases in serum cystatin-C levels, reduced renal oxidative stress, diminished Stat-3 phosphorylation and an attenuation of caspase-3 cleavage suggesting that the nanoparticle treatment improved renal glomerular filtration rate, diminished renal inflammation and reduced renal apoptosis. Consistent with these data, further analysis demonstrated that the CeO2 nanoparticle treatment diminished peritonitis-induced increases in serum kidney injury molecule-1 (KIM-1), osteopontin, β-2 microglobulin and vascular endothelial growth factor-A (VEGF-A) levels. In addition, the nanoparticle attenuated peritonitis-induced hyperglycemia along with increases in blood urea nitrogen (BUN), serum potassium and sodium. Conclusion CeO2 nanoparticles scavenge reactive oxygen species and attenuate polymicrobial insult induced increase in inflammatory mediators and subsequent AKI. Taken together, the data indicate that CeO2 nanoparticles may be useful as an alternative therapeutic agent or in conjunction with standard medical care for the treatment of peritonitis induced acute kidney injury

Cerium oxide nanoparticles inhibit lipopolysaccharide inducedMAP kinase/NF-kB mediated severe sepsis

The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The data present here provides confirmation of cerium oxide nanoparticle treatments ability to prevent the LPS induced sepsis associated changes in physiological, blood cell count, inflammatory protein and growth factors in vivo. In vitro assays investigation the treated of macrophages cells with different concentrations of cerium oxide nanoparticle demonstrate that concentration of cerium oxide nanoparticles below 1 µg/ml did not significantly influence cell survival as determined by the MTT assay

Cerium oxide nanoparticle treatment ameliorates peritonitis-induced diaphragm dysfunction

The severe inflammation observed during sepsis is thought to cause diaphragm dysfunction, which is associated with poor patient prognosis. Cerium oxide (CeO2) nanoparticles have been posited to exhibit anti-inflammatory and antioxidative activities suggesting that these particles may be of potential use for the treatment of inflammatory disorders. To investigate this possibility, Sprague Dawley rats were randomly assigned to the following groups: sham control, CeO2 nanoparticle treatment only (0.5 mg/kg iv), sepsis, and sepsis+CeO2 nanoparticles. Sepsis was induced by the introduction of cecal material (600 mg/kg) directly into the peritoneal cavity. Nanoparticle treatment decreased sepsis-associated impairments in diaphragmatic contractile (Po) function (sham: 25.6±1.6 N/cm2 vs CeO2: 23.4±0.8 N/cm2, vs Sep: 15.9±1.0 N/cm2 vs Sep+CeO2: 20.0±1.0 N/cm2, P2 nanoparticles may improve diaphragmatic function in the septic laboratory rat

Aberrant Methylation of p21 Gene in Lung Cancer and Malignant Pleural Mesothelioma

Suppression of p21 has been implicated in the genesis and progression of many human malignancies. DNA methylation is an important mechanism of gene silencing in human malignancies. In this study, we examined the expression status and aberrant methylaion of p21 in lung cancers and malignant pleural mesotheliomas (MPM). We used 12 small cell lung cancer (SCLC) cell lines, 13 non-small cell lung cancer (NSCLC) cell lines, 50 primary NSCLCs, 6 MPM cell lines and 10 primary MPMs. The expression and methylation of p21 was examined by reverse transcription-PCR (RT-PCR), Western blotting and methylation-specific PCR (MSP) assay. Loss of p21 protein expression was observed in 7 SCLC cell lines (58.3%), 5 NSCLC cell lines (38.5%) and 3 MPM cell lines (50%) while mRNA expression was lost in 2 SCLC cell lines (16.7%), 2 NSCLC cell lines (15.4%) and none of the MPM cell lines. Aberrant methylation of p21 was found in 8.3% of SCLC cell lines, 30.2% of NSCLCs and 6.3% of MPMs. Among primary NSCLCs, methylation in adenocarcinomas was significantly more frequent than in squamous cell carcinomas. Loss of p21 expression was frequently observed in lung cancers and MPMs and aberrant methylation was one of the mechanisms of suppression of p21, especially in NSCLCs