Recently, long non-coding RNAs (lncRNAs) are considered as critical regulators in pathogenesis progression of cerebral ischemia. In present study, lncRNA-small nucleolar RNA host gene 14 (SNHG14) was ...found upregulated in middle cerebral artery occlusion/reperfusion (MCAO/R) treated brain tissues and oxygen-glucose deprivation and reoxygenation (OGD/R) treated PC-12 cells. Interference of SNHG14 by shRNA vector enhanced neuron survival and suppressed inflammation in response to OGD/R insult. SNHG14 positively regulated the expression of Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) via acting as a sponge of microRNA (miR)-136-5p. SNHG14 promoted neurological impairment and inflammatory response through elevating the expression of ROCK1 while decreasing miR-136-5p level in OGD/R induced damage. Collectively, we illustrated that SNHG14 could be a novel strategy for treatment ischemia stoke.
It has been demonstrated that extracellular mRNA can be detected in the circulation. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of breast ...cancer patients compared to controls.
We measured miRNA in the serum of samples with and without the addition of miRNA prior to analysis. To test our RNA extraction efficiency, we spiked-in serial dilutions of single-strand C elegens miR-39 (cel-miR-39) and human miR-145 (has-miR-145) into goat serum and a 10 year old human serum specimen. We next analyzed miR-16, -145, and -155 in archived serum specimens from 21 participants, 13 of whom did and 8 of whom did not have breast cancer. We were able to detect the miRNAs from all the serum samples to which the miRNAs had been added. We were also able to detect endogenous miR-16, -145, and -155 in all serum samples. While the expression of all three miRNAs was similar in samples from healthy women compared to those with breast cancer, women with progesterone receptor (PR, p = 0.016) positive tumors had higher miR-155 expression than tumors that were negative for these receptors.
1) RNA species can be detected in archived serum; 2) miR-155 may be differentially expressed in the serum of women with hormone sensitive compared to women with hormone insensitive breast cancer. Screening serum for miRNAs that predict the presence of breast cancer is feasible, and may be useful for breast cancer detection.
•δ2H in the topsoil of grassland was distinctly higher than those in woodland.•δ18O in the topsoil of grassland was distinctly higher than those in woodland.•The lnRR were significantly different in ...alpine grasslands.•The lnRR were not significantly different in alpine woodlands.•As AGB < 100 t/hm2, the O-horizon should be considered in various vegetation types.
Hydrogen and oxygen isotopes have been widely used to investigate global hydrologic cycles. However, the most studies of soil water isotopes have overlooked the importance of O-horizon that may potentially influence the accurate evaluation of hydrologic processes, especially in the alpine ecosystem with thin soil layers. To address this knowledge gap, soils were sampled from the O-horizon and the 0–10 cm soil layer from 107 sites in the grasslands and woodlands of the Western Sichuan alpine ecosystem in order to evaluate the influence of climatic and biotic factors on the isotopic differences (expressed as the logarithmic of effect sizes, lnRR), which represented the difference of δ2H and δ18O between the O-horizon and the 0–10 cm soil layer. The isotopic differences between the O-horizon and the 0–10 cm soil layer were significantly different in the grasslands, but not in the woodlands. The influence of climatic factors on the lnRR was limited relative to the biotic factors, and the influence of climate contrasted with expectations based on an evaporation principle. Rather, aboveground biomass (AGB) was significantly correlated with the lnRR between and within the soil water from different vegetation types. Consequently, the observed differences were mainly related to the vegetation conditions that influence the microclimates within canopies. Therefore, the investigations of hydrological processes may inaccurately estimate their influences when not separately considering the especially high stable isotope values of the O-horizon in grasslands of alpine regions with thin soil layers. In particular, the influence of O-horizon should be considered in the areas where AGB is less than 100 t/hm2.
Neuroinflammation plays a critical role in ischemic stroke pathology and could be a promising target in ischemic stroke. Triggering receptor expressed on myeloid cells 2 (TREM2) is a ...microglia-specific receptor in the CNS that is involved in regulating neuroinflammation in cerebral ischemia. However, the role of TREM2 in ischemic stroke is controversial. Electroacupuncture (EA) is an effective therapy for alleviating stroke-induced neuroinflammation. Here, we found that ischemic stroke induced an increased microglial TREM2 expression, and EA treatment can further promote microglial TREM2 expression following cerebral ischemia. TREM2 overexpression was observed to play a neuroprotective role by improving the neurobehavioral deficit and reducing the cerebral infarct volume 72 h after reperfusion, whereas TREM2 silencing had the opposite effects. Moreover, the effects of EA on improving stroke outcome and suppressing neuroinflammation in the brain were reversed by TREM2 silencing. Finally, TREM2 silencing also suppressed the ability of EA to regulate the PI3K/Akt and NF-κB signaling pathways. Altogether, the results show that TREM2 could be a potential target in EA treatment for attenuating inflammatory injury following cerebral ischemia/reperfusion.
•Microglial TREM2 could be a potential target in EA treatment to attenuate inflammatory injury following cerebral ischemia/reperfusion.
Pleural fibrosis (PF) is a chronic and progressive lung disease which affects approximately 30,000 people per year in the United States. Injury and sustained inflammation of the pleural space can ...result in PF, restricting lung expansion and impairing oxygen exchange. During the progression of pleural injury, normal pleural mesothelial cells (PMCs) undergo a transition, termed mesothelial mesenchymal transition (MesoMT). While multiple components of the fibrinolytic pathway have been investigated in pleural remodeling and PF, the role of the urokinase type plasminogen activator receptor (uPAR) is unknown. We found that uPAR is robustly expressed by pleural mesothelial cells in PF. Downregulation of uPAR by siRNA blocked TGF-β mediated MesoMT. TGF-β was also found to significantly induce uPA expression in PMCs undergoing MesoMT. Like uPAR, uPA downregulation blocked TGF-β mediated MesoMT. Further, uPAR is critical for uPA mediated MesoMT. LRP1 downregulation likewise blunted TGF-β mediated MesoMT. These findings are consistent with in vivo analyses, which showed that uPAR knockout mice were protected from S. pneumoniae-mediated decrements in lung function and restriction. Histological assessments of pleural fibrosis including pleural thickening and α-SMA expression were likewise reduced in uPAR knockout mice compared to WT mice. These studies strongly support the concept that uPAR targeting strategies could be beneficial for the treatment of PF.
Ischemic stroke-induced neuroinflammation is mainly mediated by microglial cells. The nuclear factor kappa B (NF-κB) pathway is the key transcriptional pathway that initiates inflammatory responses ...following cerebral ischemia. OTULIN, a critical negative regulator of the NF-κΒ signaling pathway, exerts robust effects on peripheral immune cell-mediated inflammation and is regarded as an essential mediator for repressing inflammation in vivo. The effect of OTULIN on inflammatory responses in the central nervous system (CNS) was previously unstudied. This current study investigated the anti-inflammatory effect of OTULIN both in vitro and in vivo in ischemic stroke models.
Sprague-Dawley (SD) rats were subjected to transient middle cerebral artery occlusion (tMCAO) or an intraperitoneal injection of lipopolysaccharide (LPS). Overexpression of the OTULIN gene was utilized to observe the effect of OTULIN on ischemic stroke outcomes. The effect of OTULIN overexpression on microglia-mediated neuroinflammation was examined in rat primary microglia (PM) and in the microglial cell line N9 after induction by oxygen-glucose deprivation (OGD)-treated neuronal medium. The activation and inflammatory responses of microglia were detected using immunofluorescence, ELISA, and qRT-PCR. The details of molecular mechanism were assessed using Western blotting.
In the tMCAO rats, the focal cerebral ischemia/reperfusion injury induced a continuous increase in OTULIN expression within 72 h, and OTULIN expression was increased in activated microglial cells. OTULIN overexpression obviously decreased the cerebral infarct volume, improved the neurological function deficits, and reduced neuronal loss at 72 h after reperfusion, and it also inhibited the activation of microglia and attenuated the release of TNF-α, IL-1β, and IL-6 by suppressing the NF-κB pathway at 24 h after tMCAO. In vitro, OTULIN overexpression inhibited the microglia-mediated neuroinflammation by reducing the production of TNF-α, IL-1β, and IL-6 via depressing the NF-κB pathway in both PM and N9 cells.
OTULIN provides a potential therapeutic target for ischemic brain injury by ameliorating the excessive activation of microglial cells and neuroinflammation through repressing the NF-κB signaling pathway.
Trans-resveratrol, present in high concentration in the skin of red grapes and red wine, has a dose-dependent antiproliferative effect in vitro, prevents the formation of mammary tumors, and has been ...touted as a chemopreventive agent. Based upon in vitro studies demonstrating that trans-resveratrol downregulates the expression of 1) DNA methyltransferases and 2) the cancer promoting prostaglandin (PG)E₂, we determined if trans-resveratrol had a dose-related effect on DNA methylation and prostaglandin expression in humans. Thirty-nine adult women at increased breast cancer risk were randomized in double-blind fashion to placebo, 5 or 50 mg trans-resveratrol twice daily for 12 wk. Methylation assessment of 4 cancer-related genes (p16, RASSF-1α, APC, CCND2) was performed on mammary ductoscopy specimens. The predominant resveratrol species in serum was the glucuronide metabolite. Total trans-resveratrol and glucuronide metabolite serum levels increased after consuming both trans-resveratrol doses (P < .001 for both). RASSF-1α methylation decreased with increasing levels of serum trans-resveratrol (P = .047). The change in RASSF-1α methylation was directly related to the change in PGE₂ (P = .045). This work provides novel insights into the effects of trans-resveratrol on the breast of women at increased breast cancer risk, including a decrease in methylation of the tumor suppressor gene RASSF-1α. Because of the limited sample size, our findings should be validated in a larger study.
Isotopic heterogeneity in soil water has hindered the application of isotope compositions (δ18O and δ2H) in soil water dynamics. This heterogeneity has been suggested to be caused by soil properties ...such as organic matter (OM) and clay content. However, this is yet to be verified in field soil. We sampled the organic layer (O‐horizon soil) with highly decomposed organic material and the A‐horizon soil in western Sichuan, China, and equilibrated these samples with vapour created by unconfined labelling water. The relationship between soil properties and isotopic fractionation (εT/U) between unconfined water and the total soil water was used to determine the line‐conditioned excess (lc‐excess) and source rain of A‐horizon field soil by removing the influence of confined water. Equilibration experiments demonstrated a significant isotopic difference between the εT/U levels in the A‐horizon and O‐horizon soils, indicating that OM plays an important role in isotopic fractionation. In field samples, the lc‐excess of the unconfined A‐horizon water was, on an average, 2.5‰ higher than that of bulk soil water. The average offsets between the annual rain and the estimated source rain of soil water decreased by 5.0 and 0.5‰ for hydrogen and oxygen after removing the influence of confined water. Isotopic heterogeneity should not be ignored while examining the evaporation of soil water, soil source rain, and hence the recent ‘two water worlds’ hypothesis, which is especially true for cases in which the soils contain high levels of OM.
Organic matter content in soil was a key factor determining the isotopic inhomogeneity of soil water. Excluding the surface effect induced by organic matter may improve the application of δ18O and δ2H in hydrological study on soil.
Electroacupuncture (EA) may reduce inflammatory injury by inhibiting nuclear factor-kappa B (NF-κB) signaling pathway activation after ischemic stroke. Thus, we explored temporal and spatial ...expression of cylindromatosis (CYLD), a negative feedback inhibitor of the NF-κB signaling pathway, to learn whether CYLD is essential for EA and reduction of inflammatory injury after focal cerebral ischemia/reperfusion. A middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in male Sprague-Dawley (SD) rats and CYLD gene interference was used to investigate a potential role of neuroprotection. Rats were treated with EA (1 mA, 20 Hz for 5 min, 2 Hz for 30 min) at Baihui (GV 20), Hegu (LI 4) and Taichong (LR 3) acupoints, once daily, beginning 2 h after focal cerebral ischemia. Microglial activation and co-expression of CYLD and NF-κB were measured with immunofluorescence. Neuronal CX3CL1 expression was assayed to investigate the role of EA in the interaction between neurons and microglia via upregulation of CYLD. Then, CYLD, NF-κB p65 and p-IκBα protein expression was measured with Western blot. CYLD was mainly expressed in neurons of the peri-ischemic area after MCAO/R in rats and EA upregulated CYLD mRNA and protein from 24 to 72 h after focal cerebral ischemia/reperfusion. In addition, CYLD overexpression was positively correlated to neurobehavior and negatively connected with infarct volume and pro-inflammatory cytokines (TNF-α and IL-1β). Upregulation of CYLD by EA prevented NF-κB nuclear translocation and inhibition of neuronal CX3CL1 expression, which repressed activation of microglia. Finally, CYLD silencing significantly weakened suppression of the NF-κB signaling pathway by EA. In conclusion, upregulation of CYLD may underlie how EA could alleviate inflammatory injury after focal cerebral ischemia/reperfusion.
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