Effect of preemptive local injection of ropivocaine with dexmedetomidine on mirror pain in rats and its mechanism

AbstractObjectiveTo observe the effect of preemptive local injection of ropivocaine with dexmedetomidine on activation of glial cells and on the mirror pain in rats and its mechanism.MethodsA total of 48 adult male Sprague-Dawley rats (weighing 180 g–220 g) were included in the study and randomized into 3 groups, Group S, Group R, and Group RD1. A rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established in the three groups. Before procedures and nerve extraction, Group S (n = 16) was injected 0.9% saline locally; Group R (n = 16) was injected 0.5% ropivocaine locally, and Group RD1 (n = 16) was injected 0.5% ropivocaine in combined with 1 μg dexmedetomidine locally. After the model being established in the three groups, 8 rats were used for behavior test until 28 d, and dorsal root ganglions (DRGs) of the other 8 rats were harvested on the 3rd day after surgery. Immunofluorescent and transmission electron microscopy were used to observe the activation of glial cells in DRG, and the behavior test results in the three groups were compared.ResultsThe results showed that mechanical pain threshold in ipsilateral hind-paws of the Group S, Group R, Group RD1 animals dropped to (3.640 ± 1.963) g, (5.827 ± 1.204) g, (7.482) ± 1.412 g at 3 d respectively; while in contralateral paws dropped to (7.100 ± 1.789) g, (17.687 ± 1.112) g, (16.213 ± 1.345) g on the 3 d respectively. Immunofluorescent showed that the glial cells were activated in bilateral side DRG after surgery in 3 groups, but ipsilateral paws expressed more active glial cells than contralateral paws. Transmission electron microscopy showed that mitochondria swelling/vacuolization and lysosomes were more obvious in ipsilateral paws than contralateral paws, but Group RD1 formula could reduce glial cells activity, mitochondria swelling/vacuolization and the amount of lysosomes.ConclusionsLocal injection of ropivocaine and/or dexmedetomidine can effectively inhibit the activation of glial cells in DRG, mitigate the pathological changes of neuron in DRG and reduce mirror image pain

The LncRNA NEAT1 Accelerates Lung Adenocarcinoma Deterioration and Binds to Mir-193a-3p as a Competitive Endogenous RNA

Background/Aims: Long noncoding RNAs (lncRNAs) contribute to the development of multiple malignant tumors. Here, we focused on the biological function and underlying molecular mechanism of an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1), in lung adenocarcinoma (LUAD). Methods: In vitro experiments were conducted to determine the biological effects of NEAT1 in LUAD cells. A luciferase activity reporter assay was performed to corroborate the interaction between NEAT1 and miR-193a-3p. Data from Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA), and our in-house reverse transcription quantitative PCR (RT-qPCR) were combined to examine the expression of NEAT1 and miR-193a-3p in LUAD. To further explore the regulatory mechanism of NEAT1, we searched for putative target genes of miR-193a-3p from 12 online prediction databases and determined genes positively correlated with NEAT1 as candidate targets. Furthermore, we analyzed the expression of these selected genes using data from TCGA. Results: In vitro experiments showed that knockdown of NEAT1 in LUAD cells markedly restrained cell proliferation, invasion, and migration and stimulated cell apoptosis. The dual-luciferase reporter assay demonstrated that miR-193a-3p directly targeted NEAT1 at its 3’-UTR. We then detected NEAT1 and miR-193a-3p in LUAD cells and normal lung epithelial cells and discovered high expression of NEAT1 and low expression of miR-193a-3p in LUAD cell lines. Simultaneously, the pooled results from the GEO, Oncomine, TCGA, and in-house RT-qPCR showed that the NEAT1 expression increased while the miR-193a-3p expression decreased in LUAD tissues versus normal lung tissues. Furthermore, the USF1 gene was not only upregulated in LUAD, but also positively correlated with NEAT1, suggesting that NEAT1 may function as a ceRNA to sponge miR-193a-3p and abrogate the inhibitory effect of miR-193a-3p on USF1. Conclusions: Our findings indicate that NEAT1 plays important roles in the occurrence and progression of LUAD. It may exert its role by acting as a ceRNA to regulate miR-193a-3p

Expression Signature and Role of miR-30d-5p in Non-Small Cell Lung Cancer: a Comprehensive Study Based on in Silico Analysis of Public Databases and in Vitro Experiments

Background/Aims: The purpose of this study was to probe the clinico-pathological significance and the underlying mechanism of miR-30d-5p expression in non-small cell lung cancer (NSCLC). Methods: We initially examined the level of miR-30d-5p expression in NSCLC and non-cancer tissues using RT-qPCR. Then, a series of validation analyses including a meta-analysis of data from microarray chips in Gene Expression Omnibus (GEO), data mining of the cancer genome atlas (TCGA) and an integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies were performed to examine the clinico-pathological value of miR-30d-5p expression in NSCLC. In vitro experiments were further conducted to investigate the impact of miR-30d-5p on NSCLC cell growth. The molecular mechanism by which miR-30d-5p regulates the pathogenesis of NSCLC was probed through a bioinformatics analysis of its target genes. Moreover, dual luciferase reporter assay was conducted to verify the targeting regulatory relationship between miR-30d-5p and CCNE2. Results: Based on results from RT-qPCR, GEO meta-analysis, TCGA data mining and the integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies, miR-30d-5p expression was decreased in NSCLC tissues, and patients with NSCLC who presented with lower miR-30d-5p expression tended to display an advanced clinical progression. Significant pathways including the Mucin type O-glycan biosynthesis pathway, cell cycle pathway and cysteine and methionine metabolism pathway (all P< 0.05) revealed potential roles of the target genes of miR-30d-5p in the oncogenesis of NSCLC. Results from in vitro experiments indicated that miR-30d-5p could attenuate proliferation and viability of NSCLC cells. Among the 12 identified hub genes, nine genes including E2F3, CCNE2, SKP2, CDK6, TFDP1, LDHA, GOT2, DNMT3B and ST6GALNAC1 were validated by Pearson’s correlation test and the human protein atlas (HPA) database as targets of miR-30d-5p with higher probability. Specifically, dual luciferase reporter assay confirmed that CCNE2 was directly targeted by miR-30d-5p. Conclusion: In summary, miR-30d-5p expression is decreased in NSCLC, and it might play the role as tumor suppressor in NSCLC by regulating target genes

Inhibition of Intestinal Adenoma Formation in APCMin/+ Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta

BACKGROUND: Mutation of tumor suppressor gene, adenomatous polyposis coli (APC), is the primary molecular event in the development of most intestinal carcinomas. Animal model with APC gene mutation is an effective tool for study of preventive approaches against intestinal carcinomas. We aimed to evaluate the effect of Riccardin D, a macrocyclic bisbibenzyl compound, as a chemopreventive agent against intestinal adenoma formation in APC(Min/+) mice. METHODS: APC(Min/+) mice were given Riccardin D by p.o. gavage for 7 weeks. Mice were sacrificed, and the number, size and histopathology of intestinal polyps were examined under a microscope. We performed immunohistochemical staining, western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in intestinal polyps to investigate the mechanism of chemopreventive effect of Riccardin D. RESULTS: Riccardin D treatment resulted in a significant inhibition of intestinal adenoma formation, showing a reduction of polyp number by 41.7%, 31.1% and 44.4%, respectively, in proximal, middle and distal portions of small intestine. The activity of Riccardin D against polyp formation was more profound in colon, wherein Riccardin D decreased polyp number by 79.3%. Size distribution analysis revealed a significant reduction in large-size polyps (2-3 mm) by 40.0%, 42.5% and 33.3%, respectively, in proximal, middle and distal portions of small intestine, and 77.8% in colon. Histopathological analysis of the intestinal polyps revealed mostly hyperplastic morphology without obvious dysplasia in Riccardin D-treated mice. Molecular analyses of the polyps suggested that the inhibitory effect of Riccardin D on intestinal adenoma formation was associated with its abilities of reduction in cell proliferation, induction of apoptosis, antiangiogenesis, inhibition of the Wnt signaling pathway and suppression of inflammatory mediators in polyps. CONCLUSIONS: Our results suggested that Riccardin D exerts its chemopreventive effect against intestinal adenoma formation through multiple mechanisms including anti-proliferative, apoptotic, anti-angiogenic and anti-inflammatory activity

AGN STORM 2: V. Anomalous Behavior of the CIV Light Curve in Mrk 817

An intensive reverberation mapping campaign on the Seyfert 1 galaxy Mrk817 using the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope (HST) revealed significant variations in the response of the broad UV emission lines to fluctuations in the continuum emission. The response of the prominent UV emission lines changes over a $\sim$60-day duration, resulting in distinctly different time lags in the various segments of the light curve over the 14 months observing campaign. One-dimensional echo-mapping models fit these variations if a slowly varying background is included for each emission line. These variations are more evident in the CIV light curve, which is the line least affected by intrinsic absorption in Mrk817 and least blended with neighboring emission lines. We identify five temporal windows with distinct emission line response, and measure their corresponding time delays, which range from 2 to 13 days. These temporal windows are plausibly linked to changes in the UV and X-ray obscuration occurring during these same intervals. The shortest time lags occur during periods with diminishing obscuration, whereas the longest lags occur during periods with rising obscuration. We propose that the obscuring outflow shields the ultraviolet broad lines from the ionizing continuum. The resulting change in the spectral energy distribution of the ionizing continuum, as seen by clouds at a range of distances from the nucleus, is responsible for the changes in the line response.Comment: 20 pages, 8 figures, submitted to Ap

AGN STORM 2. I. First results: A Change in the Weather of Mrk 817

We present the first results from the ongoing, intensive, multiwavelength monitoring program of the luminous Seyfert 1 galaxy Mrk 817. While this active galactic nucleus was, in part, selected for its historically unobscured nature, we discovered that the X-ray spectrum is highly absorbed, and there are new blueshifted, broad, and narrow UV absorption lines, which suggest that a dust-free, ionized obscurer located at the inner broad-line region partially covers the central source. Despite the obscuration, we measure UV and optical continuum reverberation lags consistent with a centrally illuminated Shakura–Sunyaev thin accretion disk, and measure reverberation lags associated with the optical broad-line region, as expected. However, in the first 55 days of the campaign, when the obscuration was becoming most extreme, we observe a de-coupling of the UV continuum and the UV broad emission-line variability. The correlation recovered in the next 42 days of the campaign, as Mrk 817 entered a less obscured state. The short C IV and Lyα lags suggest that the accretion disk extends beyond the UV broad-line region. Unified

A New Look at the Scalar Meson f0(500)f_0(500) via D+→π+π−ℓ+νℓD^+\to \pi^+\pi^-\ell^+\nu_\ell Decays

Using $2.93~\mathrm{fb}^{-1}$ of $e^+e^-$ collision data collected with the BESIII detector at the center-of-mass energy of 3.773 GeV, we investigate the semileptonic decays $D^+\to \pi^+\pi^- \ell^+\nu_\ell$ ($\ell=e$ and $\mu$). The $D^+\to f_0(500)\mu^+\nu_\mu$ decay is observed for the first time. By analyzing simultaneously the differential decay rates of $D^+\to f_0(500) \mu^+\nu_\mu$ and $D^+\to f_0(500) e^+\nu_e$ in different $\ell^+\nu_\ell$ four-momentum transfer intervals, the product of the relevant hadronic form factor $f^{f_0}_{+}(0)$ and the magnitude of the $c\to d$ Cabibbo-Kobayashi-Maskawa matrix element $|V_{cd}|$ is determined to be $f_{+}^{f_0} (0)|V_{cd}|=0.0787\pm0.0060_{\rm stat}\pm0.0033_{\rm syst}$ for the first time. With the input of $|V_{cd}|$ from the global fit in the standard model, we determine $f_{+}^{f_0} (0)=0.350\pm0.027_{\rm stat}\pm0.015_{\rm syst}$. The absolute branching fractions of $D^+\to f_0(500)_{(\pi^+\pi^-)}\mu^+\nu_\mu$ and $D^+\to \rho^0_{(\pi^+\pi^-)} \mu^+\nu_\mu$ are determined as $(0.72\pm0.13_{\rm stat}\pm0.10_{\rm syst})\times10^{-3}$ and $(1.64\pm0.13_{\rm stat}\pm0.11_{\rm syst})\times 10^{-3}$. Combining these results with those of previous BESIII measurements on their semielectronic counterparts from the same data sample, we test lepton flavor universality by measuring the branching fraction ratios ${\mathcal B}_{D^+\to \rho^0 \mu^+\nu_\mu}/{\mathcal B}_{D^+\to \rho^0 e^+\nu_e}=0.88\pm0.10$ and ${\mathcal B}_{D^+\to f_0(500) \mu^+\nu_\mu}/{\mathcal B}_{D^+\to f_0(500) e^+\nu_e}=1.14\pm0.28$, which are compatible with the standard model expectation.Comment: Supplemental Materials added in this versio

First observation of the decay Λc+→nKS0π+π0\Lambda^+_c\to nK^{0}_{S}\pi^+\pi^0

Based on 4.5 fb$^{-1}$ of $e^{+}e^{-}$ collision data accumulated at center-of-mass energies between $4599.53$ MeV and $4698.82$ MeV with the BESIII detector, the decay $\Lambda_{c}^{+}\to nK_{S}^{0}\pi^+\pi^0$ is observed for the first time with a significance of $9.2\sigma$. The branching fraction is measured to be $(0.85\pm0.13\pm0.03)\%$, where the first uncertainty is statistical and the second systematic, which differs from the theoretical prediction based on isospin by 4.4$\sigma$. This indicates that there may be resonant contributions or some unknown dynamics in this decay