Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

<p>Abstract</p> <p>Background</p> <p>Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β). Matrix metalloprotease-9 (MMP-9) has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs) and up-regulation of IL-1β in dorsal root ganglia (DRGs), and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes.</p> <p>Results</p> <p>Subcutaneous morphine injection (10 mg/kg) induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after <it>Mmp9 </it>deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia.</p> <p>Conclusions</p> <p>Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.</p

5 GHz TMRT observations of 71 pulsars

We present integrated pulse profiles at 5~GHz for 71 pulsars, including eight millisecond pulsars (MSPs), obtained using the Shanghai Tian Ma Radio Telescope (TMRT). Mean flux densities and pulse widths are measured. For 19 normal pulsars and one MSP, these are the first detections at 5~GHz and for a further 19, including five MPSs, the profiles have a better signal-to-noise ratio than previous observations. Mean flux density spectra between 400~MHz and 9~GHz are presented for 27 pulsars and correlations of power-law spectral index are found with characteristic age, radio pseudo-luminosity and spin-down luminosity. Mode changing was detected in five pulsars. The separation between the main pulse and interpulse is shown to be frequency independent for six pulsars but a frequency dependence of the relative intensity of the main pulse and interpulse is found. The frequency dependence of component separations is investigated for 20 pulsars and three groups are found: in seven cases the separation between the outmost leading and trailing components decreases with frequency, roughly in agreement with radius-to-frequency mapping; in eleven cases the separation is nearly constant; in the remain two cases the separation between the outmost components increases with frequency. We obtain the correlations of pulse widths with pulsar period and estimate the core widths of 23 multi-component profiles and conal widths of 17 multi-component profiles at 5.0~GHz using Gaussian fitting and discuss the width-period relationship at 5~GHz compared with the results at at 1.0~GHz and 8.6~GHz.Comment: 46 pages, 14 figures, 8 Tables, accepted by Ap

TMRT observations of 26 pulsars at 8.6 GHz

Integrated pulse profiles at 8.6~GHz obtained with the Shanghai Tian Ma Radio Telescope (TMRT) are presented for a sample of 26 pulsars. Mean flux densities and pulse width parameters of these pulsars are estimated. For eleven pulsars these are the first high-frequency observations and for a further four, our observations have a better signal-to-noise ratio than previous observations. For one (PSR J0742-2822) the 8.6~GHz profiles differs from previously observed profiles. A comparison of 19 profiles with those at other frequencies shows that in nine cases the separation between the outmost leading and trailing components decreases with frequency, roughly in agreement with radius-to-frequency mapping, whereas in the other ten the separation is nearly constant. Different spectral indices of profile components lead to the variation of integrated pulse profile shapes with frequency. In seven pulsars with multi-component profiles, the spectral indices of the central components are steeper than those of the outer components. For the 12 pulsars with multi-component profiles in the high-frequency sample, we estimate the core width using gaussian fitting and discuss the width-period relationship.Comment: 33 pages, 49 figures, 5 Tables; accepted by Ap

Testing and Data Reduction of the Chinese Small Telescope Array (CSTAR) for Dome A, Antarctica

The Chinese Small Telescope ARray (hereinafter CSTAR) is the first Chinese astronomical instrument on the Antarctic ice cap. The low temperature and low pressure testing of the data acquisition system was carried out in a laboratory refrigerator and on the 4500m Pamirs high plateau, respectively. The results from the final four nights of test observations demonstrated that CSTAR was ready for operation at Dome A, Antarctica. In this paper we present a description of CSTAR and the performance derived from the test observations.Comment: Accepted Research in Astronomy and Astrophysics (RAA) 1 Latex file and 20 figure

Topographic beta spiral and onshore intrusion of the Kuroshio Current

Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 45 (2018): 287–296, doi:10.1002/2017GL076614.The Kuroshio intrusion plays a vitally important role in carrying nutrients to marginal seas. However, the key mechanism leading to the Kuroshio intrusion remains unclear. In this study we postulate a mechanism: when the Kuroshio runs onto steep topography northeast of Taiwan, the strong inertia gives rise to upwelling over topography, leading to a left-hand spiral in the stratified ocean. This is called the topographic beta spiral, which is a major player regulating the Kuroshio intrusion; this spiral can be inferred from hydrographic surveys. In the world oceans, the topographic beta spirals can be induced by upwelling generated by strong currents running onto steep topography. This is a vital mechanism regulating onshore intruding flow and the cross-shelf transport of energy and nutrients from the Kuroshio Current to the East China Sea. This topographic beta spiral reveals a long-term missing link between the oceanic general circulation theory and shelf dynamic theory.Strategic Priority Research Program of the Chinese Academy of Sciences Grant Numbers: XDA11020104, XDA110203052; National Natural Science Foundation of China (NSFC) Grant Numbers: 41576023, 41376030, 41476019; Foundation for Innovative Research Groups of NSFC Grant Number: 41421005; NSFC-Shandong Joint Fund for Marine Science Research Centers Grant Number: U1406401; Aoshan Sci-Tec Innovative Project of Qingdao National Laboratory for Marine Science and Technology Grant Number: 2016ASKJ02; National Key Research and Development Program of China Grant Numbers: 2017YFC1404000, 2016YFC1401601; National Key research and development Plan Sino-Australian Center for Healthy Coasts Grant Number: 2016YFE01015002018-07-1

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis.

Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. PROSPERO, CRD42023396828. [Abstract copyright: © 2023 Korea Institute of Oriental Medicine. Published by Elsevier B.V.

miR-103 Regulates Oxidative Stress by Targeting the BCL2/Adenovirus E1B 19 kDa Interacting Protein 3 in HUVECs

Oxidative stress plays a critical role in cardiovascular diseases. Salidroside, a glycoside from Rhodiola rosea, has been used as an antioxidative therapy for oxidative injury in cardiac diseases. However, the mechanism underlying its antioxidant effect needs to be elucidated. Treatment of HUVECs with H2O2 significantly decreased the expression of miR-103 in a dose- and time-dependent manner, whereas pretreatment with salidroside significantly inhibited this decrease. Subsequent analysis showed that overexpression of miR-103 abrogated cell activity and ROS production induced by H2O2. Bcl2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) was determined to be a novel miR-103 target in HUVECs. Interestingly, H2O2 treatment upregulated BNIP3 expression; in turn, this effect was inhibited by pretreatment with salidroside. Further studies confirmed that the knockdown of BNIP3 enhanced cell activity and suppressed the ROS production induced by H2O2. These results demonstrated for the first time that salidroside protects HUVECs in part by upregulating the expression of miR-103, which mediates BNIP3 downregulation and plays an important role in the cytoprotective actions