Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling

BackgroundZanthoxylum nitidum (Roxb.) DC., also named Liang Mianzhen (LMZ), one kind of Chinese herb characterized with anti-inflammatory and relieving pain potency, which is widely used to treat injuries, rheumatism, arthralgia, stomach pain and so on in China. But its mechanism related to the anti-hyperalgesic has not been reported. The aim of this study was to investigate the analgesic activity of Liang Mianzhen on mice with Complete Freund adjuvant (CFA)-induced chronic inflammatory pain. Meanwhile, the peripheral and central mechanisms of analgesic effect of Liang Mianzhen were further examined via observing the effects of Liang Mianzhen on the signal pathway associated with inflammatory induced hyperalgesia.MethodsThe inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After 1 day of CFA injection, the mice were treated with LMZ (100 mg/kg) for seven consecutive days, and the behavioral tests were measured after the daily intragastric administration of LMZ. The morphological changes on inflamed paw sections were determined by hematoxylin eosin (HE) staining. Changes in the mRNA expression levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nuclear factor κB p65 (NF-κBp65) were measured on day seven after CFA injection by using real-time quantitative PCR analysis and enzyme linked immunosorbent assay (ELISA) method, respectively. Moreover, immunohistochemistry and western blotting were used to detect extracellular regulated protein kinases 1/2 (ERK1/2) and NF-κB signal pathway activation.ResultsThe extract of LMZ (100 mg/kg) showed a significant anti-inflammatory and analgesic effect in the mice model. The paw edema volume was significantly reduced after the administration of LMZ compared to CFA group, as well as the paw tissues inflammatory damage was relived and the numbers of neutrophils in mice was reduced significantly. The CFA-induced mechanical threshold and thermal hyperalgesia value were significant improved with LMZ treatment at day three to day seven. We also found the mRNA levels of TNF-α, IL-1β, IL-6 and NF-κBp65 were down-regulate after 7 days from the LMZ treatment compared to CFA group. Meanwhile, LMZ significantly suppressed over-expression of the phosphorylation of ERK1/2 and NF-κBp65 in peripheral and central.ConclusionThe present study suggests that the extract of LMZ attenuates CFA-induced inflammatory pain by suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level

Small-molecule Targeting AMPA-mediated Excitotoxicity Has Therapeutic Effects in Mouse Models for Multiple Sclerosis

Peer reviewe

Hypotension due to Kir6.1 gain‐of‐function in vascular smooth muscle

BACKGROUND: K(ATP) channels, assembled from pore‐forming (Kir6.1 or Kir6.2) and regulatory (SUR1 or SUR2) subunits, link metabolism to excitability. Loss of Kir6.2 results in hypoglycemia and hyperinsulinemia, whereas loss of Kir6.1 causes Prinzmetal angina–like symptoms in mice. Conversely, overactivity of Kir6.2 induces neonatal diabetes in mice and humans, but consequences of Kir6.1 overactivity are unknown. METHODS AND RESULTS: We generated transgenic mice expressing wild‐type (WT), ATP‐insensitive Kir6.1 [Gly343Asp] (GD), and ATP‐insensitive Kir6.1 [Gly343Asp,Gln53Arg] (GD‐QR) subunits, under Cre‐recombinase control. Expression was induced in smooth muscle cells by crossing with smooth muscle myosin heavy chain promoter–driven tamoxifen‐inducible Cre‐recombinase (SMMHC‐Cre‐ER) mice. Three weeks after tamoxifen induction, we assessed blood pressure in anesthetized and conscious animals, as well as contractility of mesenteric artery smooth muscle and K(ATP) currents in isolated mesenteric artery myocytes. Both systolic and diastolic blood pressures were significantly reduced in GD and GD‐QR mice but normal in mice expressing the WT transgene and elevated in Kir6.1 knockout mice as well as in mice expressing dominant‐negative Kir6.1 [AAA] in smooth muscle. Contractile response of isolated GD‐QR mesenteric arteries was blunted relative to WT controls, but nitroprusside relaxation was unaffected. Basal K(ATP) conductance and pinacidil‐activated conductance were elevated in GD but not in WT myocytes. CONCLUSIONS: K(ATP) overactivity in vascular muscle can lead directly to reduced vascular contractility and lower blood pressure. We predict that gain of vascular K(ATP) function in humans would lead to a chronic vasodilatory phenotype, as indeed has recently been demonstrated in Cantu syndrome

External Stimuli Mediate Collective Rhythms: Artificial Control Strategies

The artificial intervention of biological rhythms remains an exciting challenge. Here, we proposed artificial control strategies that were developed to mediate the collective rhythms emerging in multicellular structures. Based on noisy repressilators and by injecting a periodic control amount to the extracellular medium, we introduced two typical kinds of control models. In one, there are information exchanges among cells, where signaling molecules receive the injected stimulus that freely diffuses toward/from the intercellular medium. In the other, there is no information exchange among cells, but signaling molecules also receive the stimulus that directionally diffuses into each cell from the common environment. We uncovered physical mechanisms for how the stimulus induces, enhances or ruins collective rhythms. We found that only when the extrinsic period is close to an integer multiplicity of the averaged intrinsic period can the collective behaviors be induced/enhanced; otherwise, the stimulus possibly ruins the achieved collective behaviors. Such entrainment properties of these oscillators to external signals would be exploited by realistic living cells to sense external signals. Our results not only provide a new perspective to the understanding of the interplays between extrinsic stimuli and intrinsic physiological rhythms, but also would lead to the development of medical therapies or devices

The Identification of Lymphocyte-Like Cells and Lymphoid-Related Genes in Amphioxus Indicates the Twilight for the Emergency of Adaptive Immune System

To seek evidence of a primitive adaptive immune system (AIS) before vertebrate, we examined whether lymphocytes or lymphocyte-like cells and the related molecules participating in the lymphocyte function existed in amphioxus. Anatomical analysis by electron microscopy revealed the presence of lymphocyte-like cells in gills, and these cells underwent morphological changes in response to microbial pathogens that are reminiscent of those of mammalian lymphocytes executing immune response to microbial challenge. In addition, a systematic comparative analysis of our cDNA database of amphioxus identified a large number of genes whose vertebrate counterparts are involved in lymphocyte function. Among these genes, several genes were found to be expressed in the vicinity of the lymphocyte-like cells by in situ hybridization and up-regulated after exposure to microbial pathogens. Our findings in the amphioxus indicate the twilight for the emergency of AIS before the invertebrate-vertebrate transition during evolution

Nonlinear Model Predictive Control of Single-Link Flexible-Joint Robot Using Recurrent Neural Network and Differential Evolution Optimization

A recurrent neural network (RNN) and differential evolution optimization (DEO) based nonlinear model predictive control (NMPC) technique is proposed for position control of a single-link flexible-joint (FJ) robot. First, a simple three-layer recurrent neural network with rectified linear units as an activation function (ReLU-RNN) is employed for approximating the system dynamic model. Then, using the RNN predictive model and model predictive control (MPC) scheme, an RNN and DEO based NMPC controller is designed, and the DEO algorithm is used to solve the controller. Finally, comparing numerical simulation findings demonstrates the efficiency and performance of the proposed approach. The merit of this method is that not only is the control precision satisfied, but also the overshoots and the residual vibration are well suppressed

Adding Growth-Promoting Ingredients in Activated Sludge Process as a Troubleshooting Strategy for Pulp and Paper Mill Wastewater Treatment

The activated sludge process is a well-established technology in the secondary treatment of pulp and paper mill wastewater. Maintaining the activities of microorganisms and allowing them to thrive, metabolize, and grow robustly is essential for efficient biological reactions. To this end, a scientific formulation of growth-promoting ingredients (containing stimulants, buffers, micronutrients, etc) provides a useful strategy for addressing the impact of fluctuations in process conditions involved in the pulp and paper production. Lots of potential exists in terms of the use of these “smart” ingredients to meet stricter discharge limits

Anaerobic Digestion for Use in the Pulp and Paper Industry and Other Sectors: An Introductory Mini-Review

Anaerobic digestion is a well-established biological process for converting biomass in waste streams into a renewable energy source, and it also contributes to the treatment of these waste streams. In this introductory mini-review, some fundamental aspects of anaerobic digestion for use in the pulp and paper industry and other sectors are briefly summarized. The contents include the basics of anaerobic digestion, feedstocks, key process parameters, and typical anaerobic digesters/reactors and their representative manufactures. Fostering the more efficient and widespread commercial use of anaerobic digestion technologies would be a critical strategy to address the issues of energy, the environment, and sustainability

Identification of the ribosomal proteins S20 and L10 from the amphioxus Branchiostoma belcheri tsingtaunese (Cephalochordata/Branchiostomidae)

231-237The complete cDNA and deduced amino acid sequences of the ribosomal protein S20 (AmphiS20) and L10 (AmphiL10) from the amphioxus Branchiostoma belcheri tsingtaunese are presented here. The AmphiS20 cDNA consists of 591 base pair (bp) and encodes a 121 amino acid protein with a calculated molecular mass of 13,621 Da. The putative protein shares 65.6%-86.6% identity to the known eukaryotic homologues including animals, plants and fungi. The AmphiL10 cDNA is 763 bp in length and encodes a 217 amino acid protein with a calculated molecular mass of 24,751Da. The deduced protein displays more than 65.4% sequence identity to its homologues examined. The high idenitity of AmphiS20 and AmphiL10 to their homologues from evolutionarily diverse organisms points to the remarkably conserved role these proteins play in ribosome structure and function. As house-keeping genes, determination of AmphiS20 and AmphiL10 will provide valuable normalizing tools for the study of transcriptional expression of other genes in amphioxus

SWBNet: A Stable White Balance Network for sRGB Images

The white balance methods for sRGB images (sRGB-WB) aim to directly remove their color temperature shifts. Despite achieving promising white balance (WB) performance, the existing methods suffer from WB instability, i.e., their results are inconsistent for images with different color temperatures. We propose a stable white balance network (SWBNet) to alleviate this problem. It learns the color temperature-insensitive features to generate white-balanced images, resulting in consistent WB results. Specifically, the color temperatureinsensitive features are learned by implicitly suppressing lowfrequency information sensitive to color temperatures. Then, a color temperature contrastive loss is introduced to facilitate the most information shared among features of the same scene and different color temperatures. This way, features from the same scene are more insensitive to color temperatures regardless of the inputs. We also present a color temperature sensitivity-oriented transformer that globally perceives multiple color temperature shifts within an image and corrects them by different weights. It helps to improve the accuracy of stabilized SWBNet, especially for multiillumination sRGB images. Experiments indicate that our SWBNet achieves stable and remarkable WB performance