Extracellular lncRNAs secreted and absorbed by cardiomyocytes.

Exosomes are membrane-surrounded extracellular vesicles released by almost all cell types, which mediate intercellular communications by delivering bioactive molecules from secretory cells to recipient cells. Long noncoding RNAs (lncRNAs) are a large class of non-(protein)-coding RNAs with lengths exceeding 200 nucleotides that are very active in the development of cardiovascular diseases (CVDs). Increasing evidence suggests that exosomal lncRNAs also play important roles in the progress of CVDs. We focus on the current available studies regarding these extracellular lncRNAs secreted and absorbed by cardiomyocytes and their functional roles in CVDs, hopefully providing a basis for deeper understanding of the pathological mechanisms of CVDs and their potential for clinical diagnosis and therapy.

Alveolar Type II Cell Damage and Nrf2-SOD1 Pathway Downregulation Are Involved in PM2.5-Induced Lung Injury in Rats.

The general toxicity of fine particulate matter (PM2.5) has been intensively studied, but its pulmonary toxicities are still not fully understood. To investigate the changes of lung tissue after PM2.5 exposure and identify the potential mechanisms of pulmonary toxicity, PM2.5 samples were firstly collected and analyzed. Next, different doses of PM2.5 samples (5 mg/kg, 10 mg/kg, 20 mg/kg) were intratracheally instilled into rats to simulate lung inhalation of polluted air. After instillation for eight weeks, morphological alterations of the lung were examined, and the levels of oxidative stress were detected. The data indicated that the major contributors to PM2.5 mass were organic carbon, elemental carbon, sulfate, nitrate, and ammonium. Different concentrations of PM2.5 could trigger oxidative stress through increasing reactive oxygen species (ROS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, and decreasing expression of antioxidant-related proteins (nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1 (SOD1) and catalase). Histochemical staining and transmission electron microscopy displayed pulmonary inflammation, collagen deposition, mitochondrial swelling, and a decreasing number of multilamellar bodies in alveolar type II cells after PM2.5 exposure, which was related to PM2.5-induced oxidative stress. These results provide a basis for a better understanding of pulmonary impairment in response to PM2.5.

Effects of domestic solid fuel combustion emissions on the biomarkers of homemakers in rural areas of the Fenwei Plain, China.

BACKGROUND: The health effects of heavy solid fuel use in winter in rural China are of concern. The effects of air pollution resulting from domestic solid fuel combustion in rural households on rural homemakers' biomarkers were revealed in this study. METHODS: In total, 75 female homemakers from rural areas of Guanzhong Basin, the Fenwei Plain, People's Republic of China, were randomly selected and divided into three groups (biomass users, coal users, and nonusers of solid fuel user [control group]). The differences in biological indicators, including 8-hydrox-2'-deoxyguanosine (8-OHdG), interlukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in urine samples as well as blood pressure (BP, including systolic BP [SBP] and diastolic BP [DBP]) and heart rate (HR) among the groups in winter and summer were investigated using statistical analysis. RESULTS: IL-6, 8-OHdG, HR, SBP, and DBP were significantly higher in winter than in summer (P < 0.05) owing to the poor air quality resulted from the excessive use of solid fuels in winter. Significant seasonal differences in 8-OHdG were observed for both coal and biomass users. After the influence of confounders was removed, only IL-6 levels in the urine of solid fuel users were significantly higher than that of the control group. CONCLUSIONS: IL-6 is a sensitive biomarker representing inflammatory responses to particulate matter emitted through household solid fuel combustion. Locally, excessive use of solid fuels in winter posed serious PM2.5 pollution in this area and adverse effects on inflammatory biomarkers in these rural homemakers and induced DNA damage related to oxidative stress.

Personal exposure to PM2.5-bound organic species from domestic solid fuel combustion in rural Guanzhong Basin, China: Characteristics and health implication.

Domestic solid fuels combustion produces a mass of fine particulate matter (PM2.5). PM2.5-bound organics, including polycyclic aromatic hydrocarbons (PAHs), oxygenated-PAHs (OPAHs), phthalate esters (PAEs) and hopanes, were quantified in indoor, outdoor and personal exposure samples collected in rural Guanzhong Basin, China. The average concentration of total quantified PAHs in personal exposure samples was 310 ±â€¯443 ng m-3, 1.5 times of those of indoor (211 ±â€¯120 ng m-3) and outdoor (189 ±â€¯115 ng m-3). Similar observations were found for the OPAHs and PAEs, i.e., much higher concentrations were seen in personal exposure samples. Hopanes average personal exposure concentration (13 ±â€¯9.7 ng m-3) was comparable to indoors (15 ±â€¯9.7 ng m-3) and outdoors (13 ±â€¯9.6 ng m-3). Among four common heating ways applied in Chinese dwelling, the highest exposure levels to PAHs, OPAHs and PAEs were found for indoor coal chunks stoves. Concentration under electric power was 1.2-4.5 folds lower than those with solid fuels in this study, proved to be the cleanest energy for the household heating. The exposures to PM2.5 on cell viabilities were also investigated. The largest reduction of 70% on cell viabilities was seen for indoor coal chunks stove housewives, indicating that the emissions from coal combustion had the greatest cytotoxic effects. The results evidenced that the heating ways in rural area could greatly impact on the housewife health in northwestern China. Advanced heating technology and protection should be conducted to reduce the personal exposures to PM2.5 from domestic solid fuel combustions.

Circulating long noncoding RNAs as novel biomarkers of human diseases.

Long noncoding RNAs (lncRNAs) are a kind of noncoding RNAs which are longer than ˜200 nucleotides, lacking of protein-encoding capacity and are implicated in the pathogenesis of various diseases. Recently, it was demonstrated that lncRNAs could be released into the circulation and be stable in blood. Circulating lncRNAs have been reported to have potential in distinguishing patients from healthy individuals. Therefore, the detection of circulating lncRNAs may be valuable for improving the diagnosis and prognosis of various diseases. This review summarized the current understanding of circulating lncRNAs as novel biomarkers of various human diseases, such as cancer, cardiovascular diseases, nervous system diseases and other diseases, which highlighted the significance of circulating lncRNAs as novel diagnostic and prognostic biomarkers of human diseases.

Prevalence of Selenium, T-2 Toxin, and Deoxynivalenol in Kashin-Beck Disease Areas in Qinghai Province, Northwest China.

The aim of this study was to determine the levels of selenium, T-2 toxin, and deoxynivalenol (DON) contamination in Kashin-Beck disease (KBD) areas and provide information for understanding the high prevalence of KBD in Qinghai Province. A total of 183 subjects were chosen in a KBD-prevalent county (Guide County) and a non-KBD county (Huangzhong County) in Qinghai Province, northwestern China, and the samples of wheat flour, soil, drinking water and blood, urine, and hair of children were collected from these residents. The selenium concentrations from all these sources were determined using atomic fluorescence spectrophotometry. The levels of T-2 toxin and DON contamination in the wheat flour samples were assayed using HPLC-MS/MS. The average selenium content in the soil, drinking water, and wheat flour samples from KBD areas were 26.93 ± 10.06 µg/kg, 0.097 ± 0.038 µg/L, and 9.50 ± 7.17 µg/kg, respectively. Among these, the selenium levels in the drinking water and wheat flour samples from the KBD endemic county were significantly lower than those from the non-KBD county. For the selenium nutrient status, only the hair selenium concentration of children from the KBD endemic county was significantly lower than that from the non-KBD county. The contents of T-2 toxin in all wheat samples were below the detection limit (0.4 µg/kg). The levels of DON contamination in wheat flour samples from KBD and non-KBD children's households within the KBD endemic county were relatively higher, with average levels of 302 ± 49 and 280 ± 48 µg/kg, respectively. The DON level of wheat flour samples from the children's households in the non-KBD county was significantly lower than that from the KBD endemic county. These results suggest that the lower selenium status in Guide County still remains. While the selenium nutritional status of the local children has improved to some extent, partly due to the introduction of food produce from nonlocal areas. DON contamination in the wheat flour may be involved in the fluctuating high prevalence rates of KBD in children in the KBD endemic Guide County in Qinghai Province.

Rapid synthesis of isoquinolinones by intramolecular coupling of amides and ketones.

Amides and ketones were intramolecularly coupled in the presence of KOt-Bu/DMF. The reaction provided good yields of a variety of isoquinolinones. A reaction mechanism of radical addition and subsequent E2-elimination is proposed.

Disordered glycometabolism involved in pathogenesis of Kashin-Beck disease, an endemic osteoarthritis in China.

Kashin-Beck disease (KBD) is a chronic endemic osteoarthritis in China. Previous studies have suggested a role of metabolic dysfunction in causation of this disease. In this investigation, the metabolomics approach and cell experiments were used to discover the metabolic changes and their effects on KBD chondrocytes. Nuclear magnetic resonance ((1)H NMR) spectroscopy was used to examine serum samples from both the KBD patients and normal controls. The pattern recognition multivariate analysis (OSC-PLS) and quantitative analysis (QMTLS iterator) revealed altered glycometabolism in KBD, with increased glucose and decreased lactate and citrate levels. IPA biological analysis showed the centric location of glucose in the metabolic network. Massive glycogen deposits in chondrocytes and increased uptake of glucose by chondrocytes further confirmed disordered glycometabolism in KBD. An in vitro study showed the effects of disordered glycometabolism in chondrocytes. When chondrocytes were treated with high glucose, expression of type II collagen and aggrecan were decreased, while TNF-α expression, the level of cellular reactive oxygen species and cell apoptosis rates all were increased. Therefore, our results demonstrated that disordered glycometabolism in patients with KBD was linked to the damage of chondrocytes. This may provide a new basis for understanding the pathogenesis of KBD.

Systems toxicology used in nanotoxicology: mechanistic insights into the hepatotoxicity of nano-copper particles from toxicogenomics.

In some studies, nano-copper particles have been found to be acutely toxic to exposed mice, with the liver and kidney being the target tissues. However, the characteristics of subacute toxicity from repeated nano-copper exposure in rats and the molecular mechanism of its hepatotoxicity at the genomic level remain unclear. We investigated the mechanisms of nano-copper-induced hepatotoxicity, which were identified from hepatic gene expression profiles that were phenotypically anchored to conventional toxicological outcomes, and identified biomarkers of nanotoxicity caused by nano-copper. Male Wistar rats were administered nano-copper or micro-copper at different doses for five days. Subsequently, we examined conventional toxicological parameters including body weight, clinical chemistry, and histopathology, and also used microarrays to identify gene expression changes in rat liver. High dose nano-copper induced increases in alanine aminotransferase, aspartate aminotransferase, triglyceride, total bilirubin, total bile acid levels, and a decrease in body weight. Histopathological studies of the liver indicated scattered, dotted hepatocytic necrosis in all rats in the high dose nano-copper group. Identified genes from the group receiving the high dose were functionally categorized, and results showed that genes related to oxidoreductase activity, metabolism, and signal transduction were involved in the development of the observed phenotypes. The results also suggest that altered gene expression patterns induced by exposure to a low, subtoxic dose of nano-copper may reveal signs of cell stress or subtle cell injury indicative of overt toxicity at higher doses. Results in this study provide new insights into the toxicology of nano-copper particles and illustrate how toxicogenomic approaches are providing an unprecedented amount of mechanistic information on molecular responses to nano-copper, as well as how they are likely to impact hazard and risk assessment. Gene expression changes are likely to be more sensitive indicators of potential adverse effects than traditional measurements of toxicity.

Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: a rapid in vivo screening method for nanotoxicity.

Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using (1)H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose of 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid beta-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced by nano-copper. The data generated from the current study completely supports the fact that an integrated metabolomic approach is promising for the development of a rapid in vivo screening method for nanotoxicity.