Significant prognostic values of nuclear genes encoding mitochondrial complex I subunits in tumor patients.

In cancer biology, it remains still open question concerning the oncogenic versus oncosuppressor behavior of metabolic genes, which includes those encoding mitochondrial complex I (CI) subunits. The prognostic value of nuclear genome mRNAs expression of CI subunits is to be evaluated in the tumor patients. We used the Kaplan Meier plotter database, the cBio Cancer Genomics Portal, and the Oncomine in which gene expression data and survival information were from thousands of tumor patients to assess the relevance of nuclear genome mRNAs level of CI subunits to patients' survival, as well as their alterations in gene and expression level in tumors. We presented that the relative expression level of overwhelming majority of the nuclear genes of CI subunits with survival significance (overall survival, relapse free survival, progression free survival, distant metastasis free survival, post progression survival, and first progression), had consistent effects for patients in each type of four tumors separately, including breast cancer, ovarian cancer, lung cancer, and gastric cancer. However, in gene level, frequent cumulative or individual alteration of these genes could not significantly affect patients' survival and the overexpression of the individual gene was not ubiquitous in tumors versus normal tissues. Given that reprogrammed energy metabolism was viewed as an emerging hallmark of tumor, thus tumor patients' survival might potentially to be evaluated by certain threshold for overall expression of CI subunits. Comprehensive understanding of the nuclear genome encoded CI subunits may have guiding significance for the diagnosis and prognosis in tumor patients.

Elemental carbon and polycyclic aromatic compounds in a 150-year sediment core from Lake Qinghai, Tibetan Plateau, China: influence of regional and local sources and transport pathways.

Elemental carbon (EC) and polycyclic aromatic compounds (PACs) are potential proxies for the reconstruction of change in human activities and the origin of air masses in historic times. In this study, the historic deposition of char and soot (the two subtypes of EC) and PACs in a 150-year sediment core from different topographic subbasins of Lake Qinghai on the Qinghai Tibetan Plateau (QTP) were reconstructed. The objective was to explore how the variations in the concentrations of EC and PACs, in the ratios of char to soot and of oxygenated polycyclic aromatic hydrocarbons (OPAHs) to parent PAHs, and in the composition of the PAC mixtures reflect historical changes in climate and human activity and the origin of air masses arriving at the QTP. The deposition fluxes of soot in the different subbasins were similar, averaging 0.18 (range of 0.15-0.25) and 0.16 (0.13-0.23) g m(-2) year(-1), respectively, but they varied for char (averaging 0.11 and 0.22 g m(-2) year(-1), respectively), suggesting ubiquitous atmospheric deposition of soot and local river inputs of char. The different vertical distributions of the char/soot ratios in the different subbasins can be interpreted in terms of the different transport mechanisms of char and soot. An abrupt increase in soot concentrations since 1980 coincides with results from the QTP ice cores that were interpreted to be indicative of soot transport from South Asia. Similar concentration patterns of PAHs with soot and 9,10-anthraquinone/anthracene (9,10-AQ/ANT) ratios all >2.0 suggest regional PAC sources. Increasing PAH/soot ratios and decreasing 9,10-AQ/ANT ratios since the beginning of the 1970s indicate increasing local emissions. The historical trends of these diagnostic ratios indicate an increase in the fossil-fuel contribution since the beginning of the 1970s. The increase of perylene concentrations with increasing core depth and the ratio of perylene to its penta-aromatic isomers indicate that perylene originates mainly from in situ biogenic diagenesis. We demonstrate that the concentrations of EC, char, soot, and PACs in sediments can be used to reconstruct local, regional, and remote sources and transport pathways of pollutants to the QTP.

Synergistic action of oncolytic herpes simplex virus and radiotherapy in pancreatic cancer cell lines.

BACKGROUND: Despite much research in chemotherapy and radiotherapy, pancreatic adenocarcinoma remains a fatal disease, highly resistant to all treatment modalities. Recent developments in the field of herpes simplex virus (HSV) engineering have allowed the generation of a number of promising virus vectors for treatment of many cancers, including pancreatic tumours. This study examined the use of one such virus, NV1023, in combination with radiation therapy in pancreatic cancer cell lines. METHODS: HSV therapy in combination with radiotherapy was investigated in pancreatic cancer cell lines Hs766T, Panc-1 and MIA PaCa-2. Multiple therapy effect analysis was performed by computerized simulation. Mechanisms underlying synergy, such as virus replication and apoptosis, were investigated. RESULTS: The combination of NV1023 and radiation yielded a synergistic oncolytic effect in all tested pancreatic cancer cell lines, with the greatest effect achieved in MIA PaCa-2. This effect was not mediated by an increase in rapid viral replication, but by a substantial increase in apoptosis. CONCLUSION: The synergistic oncolytic actions of HSV and radiotherapy observed in pancreatic cancer cell lines encourage further testing of this multimodality treatment.

Reconstruction of atmospheric soot history in inland regions from lake sediments over the past 150 years.

Historical reconstruction of atmospheric black carbon (BC, in the form of char and soot) is still constrained for inland areas. Here we determined and compared the past 150-yr records of BC and polycyclic aromatic compounds (PACs) in sediments from two representative lakes, Huguangyan (HGY) and Chaohu (CH), in eastern China. HGY only receives atmospheric deposition while CH is influenced by riverine input. BC, char, and soot have similar vertical concentration profiles as PACs in both lakes. Abrupt increases in concentrations and mass accumulation rates (MARs) of soot have mainly occurred since ~1950, the establishment of the People's Republic of China, when energy usage changed to more fossil fuel contributions reflected by the variations in the concentration ratios of char/soot and individual PACs. In HGY, soot MARs increased by ~7.7 times in the period 1980-2012 relative to the period 1850-1950. Similar increases (~6.7 times) were observed in CH. The increase in soot MARs is also in line with the emission inventory records in the literature and the fact that the submicrometer-sized soot particles can be dispersed regionally. The study provides an alternative method to reconstruct the atmospheric soot history in populated inland areas.

Hyperdynamic circulation of arteriovenous fistula preconditions the heart and limits infarct size.

BACKGROUND: Chronic arteriovenous fistulae (AVF) create sustained hyperdynamic circulation. It is not known whether hyperdynamic circulation alters myocardial sensitivity to ischemia and reperfusion injury. We tested the hypothesis that AVF activate molecular responses that increase tolerance to infarction in dogs. METHODS: Twelve dogs were divided into two groups: 1) AVF group, where an AVF in the femoral region was done; and 2) sham-operated group (each n = 6). After 8 weeks, left ventricular performance was determined from stroke work/end-diastolic length relationship. Myocardial biopsy was obtained to determine heat-shock protein 70 and adenosine triphosphate (ATP) pool. Left anterior descending coronary artery was occluded for 90 minutes at 37 degrees C, followed by 4 hours of reperfusion. Coronary blood flow was determined using different colored microspheres. RESULTS: The fistula group showed improvement of left ventricular performance (p = 0.03). The infarct size was significantly lower in the fistula group; it was 9.2+/-2.0% in the fistula group versus 28.4+/-5.2% in the sham group (p < 0.05). ATP depletion during ischemia was less in the fistula group (p = 0.02). Regional myocardial blood flow was significantly higher in the fistula group (p = 0.03). CONCLUSIONS: Peripheral AVF improve the left ventricular performance, and decrease infarct size and ATP depletion. This protective effect is caused by the development of collaterals in the coronary circulation without expression of heat-shock protein 70.

Measurement of hemoglobin synthesis rate in vivo using a stable isotope method.

We developed a method to measure hemoglobin synthesis rate (SynHb) in humans, assuming that free glycine in the red blood cell (RBC) represents free glycine in bone marrow for hemoglobin synthesis. The present rat study examines this assumption of the method and quantifies SynHb in rats. Sprague-Dawley rats (n = 9) were studied, [2-(13)C]glycine was intravenously infused over 24 h (2.5 mg kg(-1) h(-1)), blood was drawn for glycine and heme isolation, and bone marrow was harvested for glycine isolation. Isotopic enrichments of glycine and heme were measured, fractional hemoglobin synthesis rate (fSynHb% day(-1)) was calculated, and from this a value for SynHb (mg g(-1) day(-1)) was derived. Mean body weight was 446 +/- 10 g (mean +/- SE) and hemoglobin concentration was 14 +/- 0.5 g dl(-1). At 24 h, the mean isotopic enrichment, atom percentage excess (APE), of the RBC free glycine (1.56 +/- 0.18 APE) was similar to the bone marrow (1.68 +/- 0.15 APE). The rate of incorporation of (13)C into heme increased over time from 0.0004 APE/h between 6 and 12 h, to 0.0014 APE/h between 12 and 18 h, and 0.0024 APE/h between 18 and 24 h. Consequently, fSynHb (1.19 +/- 0.32, 2.92 +/- 0.66, and 4.22 +/- 0.56% day(-1), respectively) and SynHb (0.11 +/- 0.03, 0.28 +/- 0.05, and 0.42 +/- 0.05 mg g(-1) day(-1), respectively) showed similar patterns over the 24-h study period. We conclude that (1) enrichment of free glycine in the circulating RBC approximates enrichment of bone marrow free glycine for heme formation and (2) this pattern of hemoglobin synthesis rate is reflecting the characteristic release and gradual maturation of reticulocytes in the circulation.