Metabolomic analysis of human oral cancer cells with adenylate kinase 2 or phosphorylate glycerol kinase 1 inhibition.

The purpose of this study was to use liquid chromatography-mass spectrometry (LC-MS) with XCMS for a quantitative metabolomic analysis of UM1 and UM2 oral cancer cells after knockdown of metabolic enzyme adenylate kinase 2 (AK2) or phosphorylate glycerol kinase 1 (PGK1). UM1 and UM2 cells were initially transfected with AK2 siRNA, PGK1 siRNA or scrambled control siRNA, and then analyzed with LC-MS for metabolic profiles. XCMS analysis of the untargeted metabolomics data revealed a total of 3200-4700 metabolite features from the transfected UM1 or UM2 cancer cells and 369-585 significantly changed metabolites due to AK2 or PGK1 suppression. In addition, cluster analysis showed that a common group of metabolites were altered by AK2 knockdown or by PGK1 knockdown between the UM1 and UM2 cells. However, the set of significantly changed metabolites due to AK2 knockdown was found to be distinct from those significantly changed by PGK1 knockdown. Our study has demonstrated that LC-MS with XCMS is an efficient tool for metabolomic analysis of oral cancer cells, and knockdown of different genes results in distinct changes in metabolic phenotypes in oral cancer cells

Spatiotemporal Analysis of Drought Characteristics in Song-Liao River Basin in China

The monthly accumulated precipitation and monthly average temperature of 117 meteorological stations in Song-Liao River Basin (SLRB) were used to calculate the Standardized Precipitation Evapotranspiration Indices (SPEI) to analyze the drought characteristics, including long-term trends, drought affected area, climate abrupt change, intensive drought occurrence regions, and drought durations during 1964–2013 with the support of GIS. The Area Drought Severity (ADS), a comprehensive index, is proposed to assess both the variations of drought degree and the extent of the drought affected area. The results revealed that (1) the drought happening probability and degree are rising and the affected areas of all degrees of drought have an increasing trend during the last 50 years; (2) there is a climate abrupt change which occurred in around 1994, and the area with declining SPEI is larger than that with declining SPI, which could be due to the rising temperature after the climate abrupt change; (3) all degrees of drought occurrence probability increased, and the intensive drought occurrence regions altered from the northern SLRB to the southwestern SLRB after the climate abrupt change; (4) the drought duration increased from 1994, and the increased drought durations occurred in most parts of SLRB

Analysis of Oral Microbiota Revealed High Abundance of Prevotella Intermedia in Gout Patients

Background/Aims: Microbes reside in a number of body sites, including the oral cavity, and are associated with the progression of many systemic diseases. In this study, we aimed to investigate the effects of gout and hyperuricemia (HUA) on the composition of oral microbiomes. Methods: Analysis of the oral microbiota from 12 gout patients, 11 HUA patients, and 19 healthy control subjects was performed using a deep sequencing approach, and validation of significant changes in Prevotella intermedia and Serratia marcescens in new patient cohorts was performed using quantitative PCR (qPCR). Results: Our analysis indicated that both gout and HUA significantly altered the composition of the oral microbiome in patients. Patients with gout or HUA had significantly greater levels of salivary Prevotella intermedia but significantly lower levels of Serratia marcescens than healthy control subjects. Conclusion: We demonstrated the association between the oral microbiome and gout and HUA for the first time. In particular, 16S sequencing and qPCR analysis revealed significantly higher levels of oral Prevotella intermedia in gout/HUA patients, which suggests that these patients might be at risk for the development of periodontitis

The Spatial Association of Gene Expression Evolves from Synchrony to Asynchrony and Stochasticity with Age

For multicellular organisms, different tissues coordinate to integrate physiological functions, although this systematically and gradually declines in the aging process. Therefore, an association exists between tissue coordination and aging, and investigating the evolution of tissue coordination with age is of interest. In the past decade, both common and heterogeneous aging processes among tissues were extensively investigated. The results on spatial association of gene changes that determine lifespan appear complex and paradoxical. To reconcile observed commonality and heterogeneity of gene changes among tissues and to address evolution feature of tissue coordination with age, we introduced a new analytical strategy to systematically analyze genome-wide spatio-temporal gene expression profiles. We first applied the approach to natural aging process in three species (Rat, Mouse and Drosophila) and then to anti-aging process in Mouse. The results demonstrated that temporal gene expression alteration in different tissues experiences a progressive association evolution from spatial synchrony to asynchrony and stochasticity with age. This implies that tissue coordination gradually declines with age. Male mice showed earlier spatial asynchrony in gene expression than females, suggesting that male animals are more prone to aging than females. The confirmed anti-aging interventions (resveratrol and caloric restriction) enhanced tissue coordination, indicating their underlying anti-aging mechanism on multiple tissue levels. Further, functional analysis suggested asynchronous DNA/protein damage accumulation as well as asynchronous repair, modification and degradation of DNA/protein in tissues possibly contributes to asynchronous and stochastic changes of tissue microenvironment. This increased risk for a variety of age-related diseases such as neurodegeneration and cancer that eventually accelerate organismal aging and death. Our study suggests a novel molecular event occurring in aging process of multicellular species that may represent an intrinsic molecular mechanism of aging

Survey of Tyrosine Kinase Signaling Reveals ROS Kinase Fusions in Human Cholangiocarcinoma

Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23) of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted

Incidence and Etiology of Drug-Induced Liver Injury in Mainland China

Background & Aims: We performed a nationwide, retrospective study to determine the incidence and causes of drug-induced liver injury (DILI) in mainland China.Methods: We collected data on a total of 25,927 confirmed DILI cases, hospitalized from 2012 through 2014 at 308 medical centers in mainland China. We collected demographic, medical history, treatment, laboratory, disease severity, and mortality data from all patients. Investigators at each site were asked to complete causality assessments for each case whose diagnosis at discharge was DILI (n=29,478) according to the Roussel Uclaf Causality Assessment Method.Results: Most cases of DILI presented with hepatocellular injury (51.39%; 95% CI, 50.76–52.03), followed by mixed injury (28.30%; 95% CI, 27.73–28.87) and cholestatic injury (20.31%; 95% CI, 19.80–20.82). The leading single classes of implicated drugs were traditional Chinese medicines or herbal and dietary supplements (26.81%) and anti-tuberculosis medications (21.99%). Chronic DILI occurred in 13.00% of the cases and, although 44.40% of the hepatocellular DILI cases fulfilled Hy’s Law criteria, only 280 cases (1.08%) progressed to hepatic failure, 2 cases underwent liver transplantation (0.01%), and 102 patients died (0.39%). Among deaths, DILI was judged to have a primary role in 72 (70.59%), a contributory role in 21 (20.59%), and no role in 9 (8.82%). Assuming the proportion of DILI in the entire hospitalized population of China was represented by that observed in the 66 centers where DILI capture was complete, we estimated the annual incidence in the general population to be 23.80 per 100,000 persons (95% CI, 20.86–26.74). Only hospitalized patients were included in this analysis, so the true incidence is likely to be higher.Conclusions: In a retrospective study to determine the incidence and causes of drug-induced liver injury (DILI) in mainland China, the annual incidence in the general population was estimated to be 23.80 per 100,000 persons—higher than that reported from western countries. Traditional Chinese medicines, herbal and dietary supplements, and anti-tuberculosis drugs were the leading causes of DILI in mainland Chin