Abstract Long noncoding RNAs (lncRNAs) have recently been identified to be tightly linked to diverse human diseases. However, our knowledge of Systemic Lupus Erythematosus (SLE)-related lncRNAs ...remains limited. In the present study we investigated the contribution of the lncRNA NEAT1 to the pathogenesis of SLE. Here, we found NEAT1 expression was abnormally increased in SLE patients and predominantly expressed in human monocytes. Additionally, NEAT1 expression was induced by LPS via p38 activation. Silencing NEAT1 significantly reduced the expression of a group of chemokines and cytokines, including IL-6, CXCL10, etc., which were induced by LPS continuously and in late stages. Furthermore, it was identified the involvement of NEAT1 in TLR4-mediated inflammatory process was through affecting the activation of the late MAPK signaling pathway. Importantly, there was a positive correlation between NEAT1 and clinical disease activity in SLE patients. In conclusion, the increased NEAT1 expression may be a potential contributor to the elevated production of a number of cytokines and chemokines in SLE patients. Our findings suggest lncRNA contributes to the pathogenesis of lupus and provides potentially novel target for therapeutic intervention.
Basalt-derived soils are widespread worldwide. Such soils contain high levels of heavy metals like chromium (Cr), which is a serious environmental concern. However, little is known regarding the ...enrichment and speciation of Cr during the basalt weathering process. Therefore, two basalt-derived soil profiles (Nitisol and Ferralsol) in the Leizhou Peninsula, south tropical China, were investigated to explore the redistribution and transformation of Cr during basalt weathering. All profiles could be divided into three layers: rocks, saprolites, and soils. The Nitisol and Ferralsol profiles exhibited strong (kaolinization) and extreme (laterization) degrees of weathering, respectively. Results showed that Cr concentrations in the saprolites (234 to 315 mg·kg−1) were higher than those in basalt rocks (139 to 159 mg·kg−1), indicating that Cr was enriched with the continuous loss of Si and other mobile macro-elements. While high levels of Cr were also enriched in the soils (178 to 430 mg·kg−1) accompanied with Fe. However, in the upper soils of the Ferralsol profile, the acidity and organic matter could promote the leaching of Cr. Geochemical fractions and EPMA mapping showed that chromite and olivine were the main Cr-bearing minerals in basalt, but Fe-oxides (e.g., goethite and hematite) contained the highest portion of Cr in weathered saprolites and soils. The availability of Cr in the soil was extremely low due to the high stability of Cr bound to Fe-oxides. However, the decreasing contents of Cr bound to Fe-oxides in the upper soils of the Ferralsol profile indicated that Cr could also be released during Fe leaching. In conclusion, the weathering of basalt can lead to the enrichment of Cr in Fe-(hydro)oxides, which are the main controlling minerals for Cr mobility in basalt-derived soils. Further research is needed to evaluate the effect of Fe-(hydro)oxide formation and dissolution on the release of soil Cr.
Display omitted
•Cr speciation data in the basalt weathering profile was reported for the first time.•Fe-oxides are the main Cr-bearing minerals in basalt-derived soil.•Fe-(hydro)oxides controls the Cr mobility and redistribution in the Ferralsols under acidic conditions.•Cr probably migrated as the speciation of Cr(III) from proton-promoted dissolution.
MicroRNAs (miRNAs) are widely expressed in organisms and are implicated in the regulation of most biological functions. The present study investigated the association of plasma miRNAs with the ...clinical outcomes of dual antiplatelet therapy in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Plasma miRNA levels were screened using high-throughput Illumina sequencing to evaluate the antiplatelet efficacy of clopidogrel and aspirin. Six plasma miRNAs (miR-126, miR-130a, miR-27a, miR-106a, miR-21, and miR-142) were associated with clopidogrel-treated platelet aggregation. These miRNAs were validated in a prospective cohort of 1230 CAD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). High plasma miR-142 levels were associated with a high risk of major adverse cardiovascular events (MACE), with a hazard ratio (95% confidence interval) of 1.83 (1.30-2.59) at a false discovery rate of <5%. Multivariable Cox regression analysis revealed that diabetes mellitus, heart failure, calcium channel blocker application, and a high plasma miR-142 level were independent risk factors of MACE. The levels of the six plasma miRNAs were not significantly associated with bleeding events during the 3-year follow-up. In conclusion, plasma miR-142 is potential marker to predict MACE in CAD patients after PCI.
A hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently, a novel CD11c
B-cell subset has been identified that is critical for the development of ...autoimmunity. However, the role of CD11c
B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with high autoantibody production. The purpose of this study was to explore the role of CD11c
B cells in the pathogenesis of lupus in cGVHD mice.
cGVHD was induced by an intraperitoneal injection of 5 × 10
Bm12 splenocytes into B6 mice. Flow cytometry was used to analyze mice splenocytes and human samples. Magnetic beads were used to isolate mice B cells. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in serum and supernatants.
The percentage and absolute number of CD11c
B cells was increased in cGVHD-induced lupus, with elevated levels of antichromatin immunoglobulin (Ig)G and IgG2a in sera. CD11c
plasma cells from cGVHD mice produced large amounts of antichromatin IgG2a upon stimulation. Depletion of CD11c
B cells reduced antichromatin IgG and IgG2a production. T-bet was upregulated in CD11c
B cells. Knockout of T-bet in B cells alleviated cGVHD-induced lupus. Importantly, the percentage of T-bet
CD11c
B cells increased in lupus patients and positively correlated with serum antichromatin levels.
T-bet
CD11c
B cells promoted high antichromatin IgG production in the lupus-like disease model cGVHD. In lupus patients, the percentage of T-bet
CD11c
B cells was elevated and positively correlated with antichromatin antibodies. The findings provide potential therapeutic insight into lupus disease treatment.
Coronary artery disease (CAD) is currently the leading cause of death globally, and the prevalence of this disease is growing more rapidly in the Asia-Pacific region than in Western countries. ...Although the use of metal coronary stents has rapidly increased thanks to the advancement of safety and efficacy of newer generation drug eluting stent (DES), patients are still negatively affected by some the inherent limitations of this type of treatment, such as stent thrombosis or restenosis, including neoatherosclerosis, and the obligatory use of dual antiplatelet therapy (DAPT) with unknown optimal duration. Drug-coated balloon (DCB) treatment is based on a leave-nothing-behind concept and therefore it is not limited by stent thrombosis and long-term DAPT; it directly delivers an anti-proliferative drug which is coated on a balloon after improving coronary blood flow. At present, DCB treatment is recommended as the first-line treatment option in metal stent-related restenosis linked to DES and bare metal stent. For de novo coronary lesions, the application of DCB treatment is extended further, for conditions such as small vessel disease, bifurcation lesions, and chronic total occlusion lesions, and others. Recently, several reports have suggested that fractional flow reserve guided DCB application was safe for larger coronary artery lesions and showed good long-term outcomes. Therefore, the aim of these recommendations of the consensus group was to provide adequate guidelines for patients with CAD based on objective evidence, and to extend the application of DCB to a wider variety of coronary diseases and guide their most effective and correct use in actual clinical practice.
In order to evaluate the corrosion state of power grid galvanized steel components in the atmospheric environment of Anhui Province, galvanized steel samples, which were naturally exposed for 1 and 3 ...a, respectively, were analyzed using scanning electron microscopy(SEM), energy-dispersive X-ray spectroscopy(EDX) and X-ray diffractometer(XRD) to investigate the compositions and morphologies of the corrosion products, thereby revealing their atmospheric corrosion mechanisms. Meanwhile, the corrosion rates of the galvanized steel samples were determined using the weight-loss method, combined with grey correlation analysis, to ascertain the influence law of major environmental factors on the atmospheric corrosion rate of the galvanized steel samples. Results showed that the atmospheric corrosion products of the galvanized steel samples consisted of ZnO and minor amounts of Zn5(OH)6(CO3)2 and Zn4(OH)6SO4. The surface of the corrosion layer featured cellular protrusions composed of flaky Zn5(OH)6(CO3)2 and Zn4(OH)6
MicroRNAs are universal post-transcriptional regulators in genomes. They have the ability of buffering gene expressional programs, contributing to robustness of biological systems and playing ...important roles in development, physiology and diseases. Here, we identified a microRNA, miR-125a, as a positive regulator of granulopoiesis. MiR125a knockout mice show reduced infiltration of neutrophils in the lung and alleviated tissue destruction after endotoxin challenge as a consequence of decreased neutrophil numbers. Furthermore, we demonstrated that this significant reduction of neutrophils was due to impaired development of granulocyte precursors to mature neutrophils in an intrinsic manner. We showed that Socs3, a critical repressor for granulopoiesis, was a target of miR-125a. Overall, our study revealed a new microRNA regulating granulocyte development and supported a model in which miR-125a acted as a fine-tuner of granulopoiesis.
While cochlear implantation has benefitted many patients with single-sided deafness (SSD), there is great variability in cochlear implant (CI) outcomes and binaural performance remains poorer than ...that of normal-hearing (NH) listeners. Differences in sound quality across ears-temporal fine structure (TFS) information with acoustic hearing vs. coarse spectro-temporal envelope information with electric hearing-may limit integration of acoustic and electric patterns. Binaural performance may also be limited by inter-aural mismatch between the acoustic input frequency and the place of stimulation in the cochlea. SSD CI patients must learn to accommodate these differences between acoustic and electric stimulation to maximize binaural performance. It is possible that training may increase and/or accelerate accommodation and further improve binaural performance. In this study, we evaluated lateralization training in NH subjects listening to broad simulations of SSD CI signal processing. A 16-channel vocoder was used to simulate the coarse spectro-temporal cues available with electric hearing; the degree of inter-aural mismatch was varied by adjusting the simulated insertion depth (SID) to be 25 mm (SID25), 22 mm (SID22) and 19 mm (SID19) from the base of the cochlea. Lateralization was measured using headphones and head-related transfer functions (HRTFs). Baseline lateralization was measured for unprocessed speech (UN) delivered to the left ear to simulate SSD and for binaural performance with the acoustic ear combined with the 16-channel vocoders (UN+SID25, UN+SID22 and UN+SID19). After completing baseline measurements, subjects completed six lateralization training exercises with the UN+SID22 condition, after which performance was re-measured for all baseline conditions. Post-training performance was significantly better than baseline for all conditions (
< 0.05 in all cases), with no significant difference in training benefits among conditions. Given that there was no significant difference between the SSD and the SSD CI conditions before or after training, the results suggest that NH listeners were unable to integrate TFS and coarse spectro-temporal cues across ears for lateralization, and that inter-aural mismatch played a secondary role at best. While lateralization training may benefit SSD CI patients, the training may largely improve spectral analysis with the acoustic ear alone, rather than improve integration of acoustic and electric hearing.
To evaluate the independent contribution of miRNAs to the missing heritability in CYP3A4/5 functionality and atorvastatin metabolism, the relationships among three levels of factors, namely (1) ...clinical characteristics, CYP3A4/5 genotypes, and miRNAs, (2) CYP3A4 and CYP3A5 mRNAs, and (3) CYP3A activity, as well as their individual impacts on atorvastatin metabolism, were assessed in 55 human liver tissues. MiR-27b, miR-206, and CYP3A4 mRNA respectively accounted for 20.0%, 5.8%, and 9.5% of the interindividual variations in CYP3A activity. MiR-142 was an independent contributor to the expressions of CYP3A4 mRNA (partial R(2) = 0.12, P = 0.002) and CYP3A5 mRNA (partial R(2) = 0.09, P = 0.005) but not CYP3A activity or atorvastatin metabolism. CYP3A activity was a unique independent predictor of variability of atorvastatin metabolism, explaining the majority of the variance in reduction of atorvastatin (60.0%) and formation of ortho-hydroxy atorvastatin (78.8%) and para-hydroxy atorvastatin (83.9%). MiR-27b and miR-206 were found to repress CYP3A4 gene expression and CYP3A activity by directly binding to CYP3A4 3'-UTR, while miR-142 was found to indirectly repress CYP3A activity. Our study indicates that miRNAs play significant roles in bridging the gap between epigenetic effects and missing heritability in CYP3A functionality.
OBJECTIVE:Lipid peroxidation induced by free-radical species plays a prominent role in myocardial injury following ischemia and reperfusion. However, there is a lack of data in different oxygen ...concentrations on myocardial lipid peroxidation during the early phase of reperfusion. In this study, we investigated whether ventilation with medium or normal concentration of oxygen would decrease the severity of myocardial lipid peroxidation and postresuscitation myocardial dysfunction.
DESIGN:Prospective, randomized, controlled experimental study.
SETTING:University-affiliated animal research institution.
SUBJECTS:Sixty-three healthy male Sprague-Dawley rats.
INTERVENTIONS:Animals were randomized into three groups1) 100% group, 2) 50% group, and 3) 21% group. Ventricular fibrillation was induced and untreated for 8 minutes, and defibrillation was attempted after 8 minutes of cardiopulmonary resuscitation. Ventilation with 100%, 50%, or 21% oxygen was initiated in all groups during cardiopulmonary resuscitation and 1 hour following the return of spontaneous circulation. Normoxic ventilation was maintained thereafter.
MEASUREMENTS AND MAIN RESULTS:Myocardial function, including ejection fraction and myocardial performance index, were measured at baseline, 4, or 72 hours after resuscitation. Blood samples were drawn at baseline, 15 minutes, 1, 4, or 72 hours after resuscitation for the measurements of blood gas or biomarkers. Significantly better myocardial function and longer duration of survival were observed in the 50% group. Compared with the 21% and 100% groups, a mild hyperoxia and greater oxygen extraction with lower 8-iso-prostaglandin F2α were observed in the 50% group. Pearson correlation analysis confirmed that 8-iso-prostaglandin F2α was positively correlated with myocardial performance index at 4 hours postresuscitation.
CONCLUSIONS:In a rat model of cardiac arrest and resuscitation, ventilation with 50% inspired oxygen during early postischemic reperfusion phase contributed to a decreased lipid peroxidation and a better myocardial function and duration of survival.
PDF
