Summary Objective Increased activity of histone deacetylase 2 (HDAC2) has been found in patients with osteoarthritis (OA) and cartilage matrix degradation and has been shown to mediate the repression ...of cartilage-specific gene expression in human chondrocytes. We aimed to determine whether microRNA-92a-3p (miR-92a-3p) regulates cartilage-specific gene expression via targeted HDAC2 in chondrogenesis and degradation. Methods miR-92a-3p expression was assessed in vitro in a human mesenchymal stem cells (hMSCs) model of chondrogenesis and in normal and OA primary human chondrocytes (PHCs), and in normal and OA human cartilage by in situ hybridization. hMSCs and PHCs were transfected with miR-92a-3p or its antisense inhibitor (anti-miR-92a-3p), respectively. PHCs were transfected with miR-92a-3p or anti-miR-92a-3p for 24 h before chromatin immunoprecipitation assay was performed with anti-ac-H3 antibody. Direct interaction between miR-92a-3p and its putative binding site in the 3’ untranslated region (3’-UTR) of HDAC2 mRNA was confirmed by luciferase reporter assay. Results miR-92a-3p expression was elevated in chondrogenic and hypertrophic hMSC, while reduced in OA cartilage compared with normal cartilage. The overexpression of miR-92a-3p suppressed the activity of a reporter construct containing the 3’-UTR and inhibited HDAC2 expression in both hMSCs and PHCs, while treatment with anti-miR-92a-3p enhanced HDAC2 expression. Chromatin immunoprecipitation assays showed that miR-92a-3p enhances H3 acetylation on ACAN, COMP and Col2a1 promoter, and also promotes relative cartilage matrix expression. Conclusion Our results suggest that miR-92a-3p regulates cartilage development and homeostasis, which directly targets HDAC2, indicating histone hyperacetylation plays an important role in increased expression of cartilage matrix.
Objective
Emerging evidence suggests that inflammatory cytokines are involved in pathophysiology of epilepsy. However, possible interaction between the cytokines and active epilepsy remains unclear. ...This study aimed to interictal and postictal plasma cytokines in active epilepsy patients.
Materials and methods
We enrolled 48 patients with active epilepsy and 30 healthy adults and measured postictal and interictal interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), interferon gamma (IFN‐γ), interleukin‐10 (IL‐10), and interleukin‐17A (IL‐17A) concentrations in peripheral blood by enzyme‐linked immunosorbent assay (ELISA).
Results
We found postictal and interictal concentrations of IL‐6, IL‐17A, and IFN‐γ were significantly elevated in epilepsy patients compared with healthy controls. There were no significant postictal and interictal alterations of IL‐1β, IL‐6, TNF‐α, IFN‐γ, IL‐10, and IL‐17A in patients with generalized seizures compared to those with partial seizures, in carbamazepine (CBZ)‐treated patients compared to valproic acid (VPA)‐treated patients or in temporal lobe epilepsy (TLE) patients compared to extra‐temporal lobe epilepsy (eTLE) patients. Furthermore, multivariate linear regression analysis revealed that interictal IL‐17A concentration positively correlated with National Hospital Seizure Severity Scale (NHS3) scores (B=0.092, P=.007) and seizure frequency (B=0.045, P=.000). Interictal IFN‐γ concentration was also showed positively correlation with seizure frequency (B=0.019, P=.004).
Conclusions
Our data suggest that postictal and interictal various inflammatory cytokines are elevated in plasma of active epilepsy patients. Furthermore, interictal IL‐17A and IFN‐γ may predict seizure severity.
Carbon fibre reinforced plastic (CFRP) recycling and the reutilisation of the recovered carbon fibre (rCF) can compensate for the high impacts of virgin carbon fibre (vCF) production. In this paper, ...we evaluate the energy and environmental impacts of CF recycling by a fluidised bed process and reuse to manufacture a CFRP material. A ‘gate-to gate’ life cycle model of the CFRP recycling route using papermaking and compression moulding methods is developed based on energy analysis of the fluidised bed recycling process and processing of rCF. Key recycling plant operating parameters, including plant capacity, feed rate, and air in-leakage are investigated. Life cycle impact assessments demonstrate the environmental benefits of recycled CFRP against end of life treatments-landfilling, incineration. The use of rCF to displace vCF based on material indices (equivalent stiffness and equivalent strength) therefore proves to be a competitive alternative for composite manufacture in terms of environmental impact.
Climate has a considerable influence on tree growth. Forest managers benefit from the empirical study of the historic relationship between climatic variables and tree growth to support forest ...management frameworks that are to be applied under scenarios of climate change. Through this research, we have utilized long-term permanent sample plot records, historic climate data sets, and linear mixed modelling techniques to evaluate the historic influence of climatic variables on the growth rates of major boreal tree species in Newfoundland and Labrador, Canada. For the commercially significant spruce and fir forests of the province, we found growing degree-days (GDD) to negatively correlate with tree productivity in warmer regions, such as much of Newfoundland (±1350 GDD), but positively correlate with growth in cooler regions, such as those in Labrador (±750 GDD). With respect to precipitation, environmental moisture was not on average a limiting factor to species productivity in the province. These dynamics have implications for the productivity of the spruce–fir forests of the study area when considered alongside contemporary climate projections for the region, which generally entail both a warmer and wetter growing environment.
Summary Objective The association between smoking and the risk for knee osteoarthritis (OA) remains controversial. Here we present a systematic review and meta-analysis of this relationship. Design ...Cohort, case-control, and cross-sectional studies were obtained from the Medline, Embase, and Web of Science databases. Estimates were calculated using a random-effects model. Subgroup analyses and meta-regression models were performed to investigate potential sources of heterogeneity. We further analyzed the dose-response relationship between cigarette consumption and risk of knee OA. Results Thirty-eight independent observational studies that included 481,744 participants were analyzed. Those who had ever smoked had a significantly decreased risk of developing knee OA relative to those who had never smoked (RR=0.80; 95%CI 0.73 to 0.88). This was unaffected by study design, and the pooled RRs were 0.79 (95%CI, 0.65 to 0.96), 0.71 (95%CI, 0.61 to 0.84) and 0.83 (95%CI, 0.73 to 0.94) for cohort, case-control, and cross-sectional studies, respectively. Analysis of subgroups stratified by gender reduced the heterogeneity from moderate to low in both males and females. The lower risk for developing knee OA was more apparent in male smokers (RR=0.69; 95%CI 0.58 to 0.80) than female smokers (RR=0.89; 95%CI 0.77 to 1.02) and dose-response analysis showed a linear decrease in knee OA with increased cigarette consumption. Conclusions We found an inverse association between cigarette smoking and risk of knee OA, irrespective of study design. This association was more apparent in males. However, we have not demonstrated a causal relationship between smoking and OA, and further investigations are needed.
The brain endothelium is an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. Previously, we documented the important regulatory roles of microRNAs in ...the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown.
Using RNA sequencing (RNA-seq) technology, we profiled long non-coding RNA (lncRNA) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen–glucose deprivation (OGD), an in vitro mimic of ischemic stroke conditions. After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Among them, the most highly upregulated lncRNAs include Snhg12, Malat1, and lnc-OGD 1006, whereas the most highly downregulated lncRNAs include 281008D09Rik, Peg13, and lnc-OGD 3916. Alteration of the most highly upregulated/downregulated ODG-responsive lncRNAs was further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice following transient middle cerebral artery occlusion (MCAO) and 24h reperfusion by the quantitative real-time PCR approach. Moreover, promoter analysis of altered ODG-responsive endothelial lncRNA genes by bioinformatics showed substantial transcription factor binding sites on lncRNAs, implying potential transcriptional regulation of those lncRNAs. These findings are the first to identify OGD-responsive brain endothelial lncRNAs, which suggest potential pathological roles for these lncRNAs in mediating endothelial responses to ischemic stimuli. Endothelial-selective lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.
•A first study to profile ischemic-responsive brain endothelial long non-coding RNAs•Total 217 lncRNAs were classified as ischemic-responsive endothelial lncRNAs.•The most highly altered lncRNAs were confirmed in brain microvessels after stroke.•Identified key transcription factors that regulate ischemic-responsive lncRNAs
Segregations of carbonates in association with chlorapatite were discovered in garnet peridotites of the Marun-Keu eclogite–gneiss complex (Polar Urals) for the first time. They contain relics of ...dolomite, which is replaced by calcite with symplectite (graphic) ingrowths of brucite and bicarbonate. The formation of peridotites with unusual carbonate structures is the result of the evolution of the rocks from this complex at different depths. During deep subduction and progressive metamorphism followed by the formation of garnet peridotites, segregated dolomite underwent solid-phase breakdown into aragonite and magnesite at the pressure peak (≥5 GPa). During exhumation and retrograde metamorphism, garnet peridotites, together with segregations, experienced further transformation; aragonite was replaced by calcite, and magnesite, by brucite and bicarbonate. The presence of carbonates with deep-seated structures confirms that the garnet peridotites and eclogites of the Polar Urals belong to ultrahigh-pressure complexes.
Understanding how flowering phenology responds to warming and cooling (i.e., symmetric or asymmetric response) is needed to predict the response of flowering phenology to future climate change that ...will happen with the occurrence of warm and cold years superimposed upon a long-term trend. A three-year reciprocal translocation experiment was performed along an elevation gradient from 3200 m to 3800 m in the Tibetan Plateau for six alpine plants. Transplanting to lower elevation (warming) advanced the first flowering date (FFD) and transplanting to higher elevation (cooling) had the opposite effect. The FFD of early spring flowering plants (ESF) was four times less sensitive to warming than to cooling (by −2.1 d/°C and 8.4 d/°C, respectively), while midsummer flowering plants (MSF) were about twice as sensitive to warming than to cooling (−8.0 d/°C and 4.9 d/°C, respectively). Compared with pooled warming and cooling data, warming alone significantly underpredicted 3.1 d/°C for ESF and overestimated 1.7 d/°C for MSF. These results suggest that future empirical and experimental studies should consider nonlinear temperature responses that can cause such warming-cooling asymmetries as well as differing life strategies (ESF vs. MSF) among plant species.
Summary Objectives Long noncoding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules involved in various biological processes, but their role in osteoarthritis (OA) remains unknown. ...Therefore, we aimed to reveal lncRNAs expression profile in human osteoarthritic cartilage and explore the potential functions of lncRNAs in OA. Methods The expression profiles of lncRNAs and mRNAs in OA cartilage were obtained using microarray and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics analyses including lncRNA classification and subgroup analysis, gene ontology (GO) analysis, pathway analysis, network analysis and target prediction were performed. Results There were 3007 upregulated lncRNAs and 1707 downregulated lncRNAs in OA cartilage compared with normal samples (Fold change ≥ 2.0). In addition, 2136 mRNAs were upregulated and 2,241 mRNAs were downregulated in OA cartilage (Fold change ≥ 2.0). The qRT-PCR results of six dysregulated lncRNAs were consistent with the microarray data. 106 lncRNAs and 291 mRNAs composed the coding-non-coding gene co-expression network (CNC network). In the 600 top differentially expressed lncRNAs, 48 lncRNAs were predicted to have more than five cis -regulated target genes and up to 530 lncRNAs might regulate their trans target genes through collaboration with transcriptional factor (TF) SP1. The positive correlation between lncRNA uc.343 and predicted target homeobox gene C8 (HOXC8) expression in SW1353 cells treating with interleukin-1 beta confirmed the target prediction to some extent. Conclusions This study revealed the expression pattern of lncRNAs in OA cartilage and predicted the potential function and targets, which indicated that lncRNAs may be new biomarkers for diagnosis or novel therapeutic targets of OA.
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