Leucine Supplementation Modulates Lipid Metabolism and Inflammation in Early Weaning Piglets.

Early weaning can induce the programmed dysregulation of glycolipid metabolism and inflammation in adult animals. The primary objective of this study was to evaluate the efficacy of leucine supplementation administered promptly after early weaning in mitigating these adverse effects in piglets. At day 21, 24 piglets were randomly selected and divided into 3 groups: EW group where the piglets were weaned at day 21 and fed basal diet, EWL group where the piglets were weaned at day 21 and fed the basal diet with supplementation of 1% leucine, and C group where the piglets were fed basal diet and weaned at 28 days. Each group contained eight replicates, with one piglet per replicate. The results indicated that early weaning had an impact on gut health and could activate the inhibitor of the kappa B kinase gamma/inhibitor kappa B alpha/NF-kappa-B (IKKγ/IκBα/NF-κB) signaling pathway to ameliorate pro-inflammatory factor and apoptosis levels. Furthermore, early weaning reduced the activity of fatty acid ß oxidation (FAßO) and affected genes linked with lipid metabolism. Supplementing with leucine can improve the effects of these factors. In summary, leucine may alleviate the influences of early weaning on the lipid metabolism and inflammation in piglets.

Highly Thermally Conductive Aramid Nanofiber Composite Films with Synchronous Visible/Infrared Camouflages and Information Encryption.

The development of highly thermally conductive composites that combine visible light/infrared camouflage and information encryption has been endowed with great significance in facilitating the application of 5G communication technology in military fields. This work uses aramid nanofibers (ANF) as the matrix, hetero-structured silver nanowires@boron nitride nanosheets (AgNWs@BNNS) prepared by in situ growth as fillers, which are combined to fabricate sandwich structured thermally conductive and electrically insulating (BNNS/ANF)-(AgNWs@BNNS)-(BNNS/ANF) (denoted as BAB) composite films by "filtration self-assembly, air spraying, and hot-pressing" method. When the mass ratio of AgNWs@BNNS to BNNS is 1 : 1 and the total mass fraction is 50 wt %, BAB composite film has the maximum in-plane thermal conductivity coefficient (λ∥ of 10.36 W/(m ⋅ K)), excellent electrical insulation (breakdown strength and volume resistivity of 41.5 kV/mm and 1.21×1015â€…Ω â‹… cm, respectively) and mechanical properties (tensile strength of 170.9 MPa). 50 wt % BAB composite film could efficiently reduce the equilibrium temperature of the central processing unit (CPU) working at full power, resulting in 7.0 °C lower than that of the CPU solely integrated with ANF directly. In addition, BAB composite film boasts adaptive visible light/infrared dual camouflage properties on cement roads and jungle environments, as well as the function of fast encryption of QR code information within 24 seconds.

Social value orientation modulates behavioral and neural responses to social influence.

Substantial studies have investigated the social influence effect; however, how individuals with different social value orientations (SVOs), prosocials and proselfs, respond to different social influences remains unknown. This study examines the impact of positive and negative social information on the responses of people with different SVOs. A face-attractiveness assessment task was employed to investigate the relationships between influence probability, memory, and event-related potentials of social influence. A significant interactional effect suggested that prosocials and proselfs reacted differently to positive (group rating was more attractive) and negative (group rating was less attractive) social influences. Specifically, proselfs demonstrated significantly higher influence probability, marginally better recall performance, smaller N400, and larger late positive potential on receiving negative influence information than on receiving positive influence information, while prosocials showed no significant differences. Overall, correlations between N400/LPP, influence probability, and recall performance were significant. The above results indicate the modulating role of SVO when responding to social influence. These findings have important implications for understanding how people conform and how prosocial behavior occurs.

Patent mining on soil pollution remediation technology from the perspective of technological trajectory.

Recent years have seen a marked growth in soil environmental problems, however, the research & development (R&D) direction of soil pollution remediation technology (SPRT) for addressing related challenges to the global ecosystem is still unclear. Patent is the most effective carrier of technological information. Therefore, this study investigates the status and future direction of SPRT through the analysis and mining of 14,475 patents from 1971 to 2020. In 2006-2020, 14,435 SPRT patents (79% of the total) were published, which is in the development stage. By measuring the proportion of high-value patents, determined by the ratio of the number of patent families containing two or more patents (PF2) to that containing at least one patent (PF1), we found that United States (PF2/PF1 = 0.711), Japan (PF2/PF1 = 0.500), and South Korea (PF2/PF1 = 0.431) hold a monopoly. International patent organizations serve as a bridge for technology transfer. Patent CN101947539-A measured by structural hole index (Effective size = 98.194, Efficiency = 0.926) has the most significant technological influence. Therefore, in order to accomplish the technological transition and improve the soil remediation capacity, more attention should be paid to the microbial-assisted phytoremediation technology related to inorganic pollutants, hyperaccumulators and stabilizers. Additionally, patents CN102834190-A (Effective size = 23.930, Efficiency = 0.855, Constraint = 0.141, Hierarchy = 0.089) and CN105855289 (Effective size = 21.453, Efficiency = 0.795 Constraint = 0.149, Hierarchy = 0.086) are both at the location of structural holes. So, more research should be carried out on green and cost-effective solutions for reducing organic pollutants in soil remediation. The current study identifies opportunities for innovations and breakthroughs in SPRT and offers relevant information on technological development prospects.

Multifunctional Thermally Conductive Composite Films Based on Fungal Tree-like Heterostructured Silver Nanowires@Boron Nitride Nanosheets and Aramid Nanofibers.

Thermal conduction for electronic equipment has grown in importance in light of the burgeoning of 5G communication. It is imperatively desired to design highly thermally conductive fillers and polymer composite films with prominent Joule heating characteristics and extensive mechanical properties. In this work, "solvothermal & in situ growth" method is carried out to prepare "Fungal tree"-like hetero-structured silver nanowires@boron nitride nanosheet (AgNWs@BNNS) thermally conductive fillers. The thermally conductive AgNWs@BNNS/ANF composite films are obtained by the method of "suction filtration self-assembly and hot-pressing". When the mass fraction of AgNWs@BNNS is 50 wt%, AgNWs@BNNS/ANF composite film presents the optimal thermal conductivity coefficient of 9.44 W/(m ⋅ K) and excellent tensile strength of 136.6 MPa, good temperature-voltage response characteristics, superior electrical stability and reliability, which promise a wide application potential in 5G electronic devices.

Technology status and trends of industrial wastewater treatment: A patent analysis.

Globally, 80% of wastewater, among which 28% came from industry, returned to the ecosystem without treatment or reuse. The discharge of industrial wastewater poses public health and environmental concerns. The necessity and urgency of industrial wastewater treatment (IWT) will bring great challenges to most countries. This paper conducted the patent analysis combined with text mining to quantitatively analyze 11,840 patents related to IWT in the Derwent Innovations Index database. The results showed that: From 1973 to 2020, the number of patents related to IWT annually was increasing consistently. China ranked first in the number of patent publications. In contrast, the United States and some patent organizations, such as World Intellectual Property Organization, produced fewer patents, while they played more important roles in knowledge transfer. The core technology analysis suggested that method, device, material and related industry were hot topics. From activated sludge treatment technology, industrial wastewater treatment technology had gone through a development process from single technology treatment to combined technologies treatment. In the foreseeable future, research on devices for physical treatment, advanced oxidation processes, automated and energy-saving treatment systems were the promising directions.

Potentilla discolor ameliorates LPS-induced inflammatory responses through suppressing NF-κB and AP-1 pathways.

Potentilla discolor Bunge (PD) is a traditional Chinese medicine which has been widely used for the treatment of various inflammatory diseases (e.g., diarrhea, fever and furuncle). However, few studies focused on its effect on classical inflammation. This study aimed to investigate the anti-inflammatory effect and potential mechanism of the ethanol extract of the whole herbs of PD (EPD) in lipopolysaccharide (LPS)-induced inflammatory models. The obtained results showed that EPD decreased supernatant NO, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) in LPS-activated RAW264.7 cells and mouse peritoneal macrophages. Moreover, its effect on NO was attributed to the suppression of iNOS expression rather than its activity. At the transcriptional level, EPD suppressed iNOS, TNF-α and MCP-1 mRNA expressions in LPS-stimulated RAW264.7 cells. Further study showed that EPD didn't affect the phosphorylation and degradation of IκBα, but yet impeded the nuclear translocation of p65 to inhibit NF-κB activation. Meanwhile, it also prevented JNK, ERK1/2 and p38 phosphorylation to dampen the activation of AP-1. In endotoxemia mouse model, EPD not only decreased interleukin-6, TNF-α and MCP-1 levels in serum, but also potently ameliorated diarrhea. These findings provide the theoretical basis for PD to treat inflammatory diseases, especially intestinal inflammation.

Forsythiasides-Rich Extract From Forsythiae Fructus Inhibits Mast Cell Degranulation by Enhancing Mitochondrial Ca2+ Uptake.

Mast cells (MCs) activated via IgE/FcεRI or MAS-related G protein coupled receptor (Mrgpr)-mediated pathway can release granules that play prominent roles in hypersensitivity reactions. Forsythiae Fructus, a well-known traditional Chinese medicine, has been clinically used for allergic diseases. Although previous studies indicated that Forsythiae Fructus extract inhibited compound 48/80-induced histamine release from MCs, its effect on IgE-dependent MC degranulation and possible underlying mechanisms remain to be explored. Herein, we prepared the forsythiasides-rich extract (FRE) and investigated its action on MC degranulation and explored its underlying mechanism. Our data showed that FRE could dampen IgE/FcεRI- and Mrgpr-mediated MC degranulation in vitro and in vivo. Mechanism study indicated that FRE decreased cytosolic Ca2+ (Ca2+ [c]) level rapidly and reversibly. Moreover, FRE decreased Ca2+ [c] of MCs independent of plasma membrane Ca2+-ATPase (PMCA), sarco/endoplasmic Ca2+-ATPase (SERCA) and Na+/Ca2+ exchanger (NCX). While, along with Ca2+ [c] decrease, the increase of mitochondrial Ca2+ (Ca2+ [m]) occurred simultaneously in FRE-treated RBL-2H3 cells. In the isolated mitochondria, FRE also promoted the subcellular organelle to uptake more extramitochondrial Ca2+. In conclusion, by increasing Ca2+ [m] uptake, FRE decreases Ca2+ [c] level to suppress MC degranulation. Our findings may provide theoretical support for the clinical application of Forsythiae Fructus on allergy and other MC-involved diseases.

Sophoraflavanone M, a prenylated flavonoid from Sophora flavescens Ait., suppresses pro-inflammatory mediators through both NF-κB and JNK/AP-1 signaling pathways in LPS-primed macrophages.

(2R)-3α,7,4'-trihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone is a prenylated flavonoid isolated from the anti-inflammatory herb Sophora flavescens Ait. We firstly named it sophoraflavanone M (SFM) in accordance with trivial names of related constitutes from this plant. Although various studies investigated the anti-inflammatory properties of prenylated flavonoids from Sophora flavescens Ait., that of SFM remains unclear and is yet to be determined. In the current study, we assessed the anti-inflammatory effects of SFM in LPS-induced in vivo and in vitro models. In the serum of endotoxemia mice, SFM significantly suppressed LPS-elevated inflammatory cytokines. Furthermore, at nontoxic concentrations, SFM reduced LPS-induced production of inflammatory mediators NO, IL-6, TNF-α, and MCP-1 in mouse primary peritoneal macrophages. Accordingly, in LPS-primed RAW264.7 cell line, it also inhibited these mediators' expression at both transcriptional and translational levels without cytotoxicity. Mechanistically, SFM is found to concurrently inhibit two important inflammatory signaling pathways, NF-κB and JNK/AP-1. SFM restrained phosphorylation and degradation of IκBα as well as the subsequent p65 translocation to dampen NF-κB activity. Meanwhile, it also suppressed JNK phosphorylation to inhibit the transcriptional activity of AP-1. These results provide material basis for traditional application of the anti-inflammatory herb Sophora flavescens Ait. and suggest SFM is a promising natural candidate for alleviating inflammatory conditions.

Aloe-emodin, a naturally occurring anthraquinone, is a highly potent mast cell stabilizer through activating mitochondrial calcium uniporter.

Mast cells play a fundamental role in immune system. Upon stimulation, they are activated via IgE dependent or independent pathway and then release granules which contain plenty of preformed constituents. Mast cell stabilizers are commonly used clinically for inhibiting the degranulation of mast cells. In the current study, we firstly identified aloe-emodin, a naturally occurring anthraquinone, was a prominent mast cell stabilizer. It could strikingly dampen IgE/FcεRI- and MAS-related G protein coupled receptor (Mrgpr)-mediated mast cell degranulation in vitro and in vivo. Mechanism study indicated that aloe-emodin rapidly and reversibly decreased cytosolic Ca2+ (Ca2+[c]) concentration through enhancing the mitochondrial Ca2+ (Ca2+[m]) uptake. After genetically silencing or pharmacologic inhibiting mitochondrial calcium uniporter (MCU), the effects of aloe-emodin on the Ca2+[c] level and mast cell degranulation were significantly weakened. In contrast to six clinical drugs with mast cell stabilizing properties (amlexanox, tranilast, ketotifen, cromolyn disodium salt, dexamethasone and pimecrolimus), aloe-emodin showed an impressive and potent inhibitory action on the mast cell degranulation. Collectively, aloe-emodin is a highly potent mast cell stabilizer. By directly activating MCU, it decreases Ca2+[c] level to suppress mast cell degranulation. Our study may provide a promising candidate for the treatment of mast cell activation-related diseases.

Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(R)-Demethyl Spirochensilide A.

A concise and diastereoselective construction of the ABCD ring system of spirochensilide A is described. The key steps of this synthesis are a semipinacol rearrangement reaction to stereoselectively construct the AB ring system bearing two vicinal quaternary chiral centers and a Co-mediated Pauson-Khand reaction to form the spiro-based bicyclic CD ring system. This chemistry leads to the stereoselective synthesis of 13(R)-demethyl spirochensilide A, paving the way for the first asymmetric total synthesis of (-)-spirochensilide A.

Penicillin causes non-allergic anaphylaxis by activating the contact system.

Immediate hypersensitivity reaction (IHR) can be divided into allergic- and non-allergic-mediated, while "anaphylaxis" is reserved for severe IHR. Clinically, true penicillin allergy is rare and most reported penicillin allergy is "spurious". Penicillin-initiated anaphylaxis is possible to occur in skin test- and specific IgE-negative patients. The contact system is a plasma protease cascade initiated by activation of factor XII (FXII). Many agents with negative ion surface can activate FXII to drive contact system. Our data showed that penicillin significantly induced hypothermia in propranolol- or pertussis toxin-pretreated mice. It also caused a rapid and reversible drop in rat blood pressure, which did not overlap with IgE-mediated hypotension. These effects could be countered by a bradykinin-B2 receptor antagonist icatibant, and consistently, penicillin indeed increased rat plasma bradykinin. Moreover, penicillin not only directly activated contact system FXII-dependently, but also promoted bradykinin release in plasma incubated-human umbilical vein endothelial cells. In fact, besides penicillin, other beta-lactams also activated the contact system in vitro. Since the autoactivation of FXII can be affected by multiple-factors, plasma from different healthy individuals showed vastly different amidolytic activity in response to penicillin, suggesting the necessity of determining the potency of penicillin to induce individual plasma FXII activation. These results clarify that penicillin-initiated non-allergic anaphylaxis is attributed to contact system activation, which might bring more effective diagnosis options for predicting penicillin-induced fatal risk and avoiding costly and inappropriate treatment clinically.

Modified clay mineral: A method for the remediation of the mercury-polluted paddy soil.

Rice is easy to accumulate mercury (Hg), especially methylmercury (MeHg) with high toxicity, and this leads to a serious health risk for residents in some Hg-polluted areas of Asia. Thus, there is an urgent need to find soil remediation techniques that can both guarantee agricultural production and protect human health in these Hg-contaminated areas. In this study, montmorillonite (Mont) and medical stone (Med) were modified by a thiol-based material (-SH) and by chitosan to obtain modified clay mineral adsorbents. Pot experiments were then performed to explore their ability to reduce the levels of Hg and MeHg in rice and their reduction mechanisms. Compared with unmodified clay minerals, modified clay minerals had better Hg reduction efficiencies in rice. The amendment of SH-modified Med (Med-SH) had the highest THg and MeHg reduction efficiencies in rice, reaching up to 78% and 81%, respectively, and brought the THg concentration in the rice below China's health guidelines for rice (20 ng g-1). Not only did amendment of the SH-modified clay minerals reduce the exchangeable and specially adsorbed Hg in the soil, as did the other amendments, but they also significantly reduced the amount of oxide-bound Hg and MeHg in the soil, and greatly enhanced the retention of Hg and MeHg in soil, thus significantly reduced the concentration of Hg and MeHg in rice.

Amlexanox exerts anti-inflammatory actions by targeting phosphodiesterase 4B in lipopolysaccharide-activated macrophages.

Amlexanox, an anti-inflammatory agent, is widely used for treating aphthous ulcers. Recently, amlexanox has received considerable attention because of its efficacy in mitigating metabolic inflammation via directly suppressing IKKε/TBK1. However, because the knockdown of IKKε/TBK1 has no anti-inflammatory effect on lipopolysaccharide (LPS)-primed RAW264.7 cells, the mechanism of amlexanox against classical inflammation is independent of IKKε/TBK1. In this study, we aim to examine the effects of amlexanox on LPS-treated macrophages and in a mouse model of endotoxemia. We found that amlexanox significantly inhibited the production of pro-inflammatory mediators, both in vitro and in vivo, while increased interleukin-10 level in LPS-activated macrophages. Mechanistically, amlexanox down-regulated nuclear factor κB and extracellular signal-regulated kinase/activator protein-1 signaling by elevating intracellular 3',5'-cyclic adenosine monophosphate (cAMP) level and subsequently activating protein kinase A. Molecular docking along with fluorescence polarization and enzyme inhibition assays revealed that amlexanox bound directly to phosphodiesterase (PDE) 4B to inhibit its activity. The anti-inflammatory effects of amlexanox could be abolished by the application of cAMP antagonist or PDE4B siRNA. In addition to PDE4B, the activities of PDE1C, 3A, and 3B were directly inhibited by amlexanox. Our results provide mechanistic insight into the clinical utility of amlexanox for the treatment of inflammatory disorders and might contribute to extending the clinical indications of amlexanox.

Isodeoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber Linn., inhibits pro-inflammatory mediators' production through both NF-κB and AP-1 pathways in LPS-activated macrophages.

Isodeoxyelephantopin (IDET) has been identified as an anti-tumor natural constituent whose anti-tumor activity and mechanism have been widely investigated. Since the occurrence and development of cancer usually accompany with inflammation, and tumor signaling shares many components with inflammation signaling, the agents with anti-tumor activity are likely to possess anti-inflammation potential. Thus, the current study aims to demonstrate the anti-inflammatory activity along with the underlying mechanism of IDET in lipopolysaccharide (LPS)-primed macrophages. By using Griess method and ELISA, we found that in both bone marrow derived macrophages and alveolar macrophage cell line, IDET, at relatively low concentrations (0.75, 1.5 and 3 µM), could inhibit LPS-induced expression of various pro-inflammatory mediators including nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS), interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1) and IL-1ß. Meanwhile, in activated MH-S cells, the inhibitory action of IDET on mRNA expression levels of these cytokines was also detected using qPCR. Mechanistically, the effects of IDET on two key inflammatory signalings, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) pathways, were determined in LPS-activated MH-S cells by reporter gene along with western blot assays. On the one hand, IDET suppressed NF-κB signaling via down-regulating phosphorylation and degradation of inhibitor of NF-κB (IκB)-α and the subsequent p65 translocation. On the other hand, IDET dampened AP-1 signaling through attenuating phosphorylation of both c-jun N-terminal kinase 1/2 (JNK1/2) and extracellular signal regulated kinase 1/2 (ERK1/2). Our study indicates that IDET might be a promising constituent from the anti-inflammatory herb Elephantopus scaber Linn. in mitigating inflammatory conditions, especially respiratory inflammation.

Ethanol extract of Elephantopus scaber Linn. Attenuates inflammatory response via the inhibition of NF-κB signaling by dampening p65-DNA binding activity in lipopolysaccharide-activated macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Elephantopus scaber Linn. (E.scaber) is a widely-used traditional herb whose use has been documented for various inflammatory diseases such as fever, sore throat, dysentery, carbuncle and so on. However, the effect and mechanism of E.scaber in LPS-activated macrophages remain unclear. AIM: This study aims to investigate the anti-inflammatory mechanism of the ethanol extract of E.scaber (ESE) in lipopolysaccharide (LPS)-induced inflammatory models. MATERIALS AND METHODS: Griess reagent was used to determine NO production, and the levels of TNF-α, IL-6, MCP-1 and IL-1ß were determined by ELISA kits. The molecular mechanism research was performed by RT-PCR, Western blot, and electrophoretic mobility shift assay (EMSA). LPS-induced endotoxemia mouse model was used for evaluating the in vivo anti-inflammatory action of ESE. RESULTS: ESE suppressed LPS-induced iNOS, TNF-α, IL-6, MCP-1 and IL-1ß transcription as well as supernatant NO, TNF-α, IL-6, MCP-1 and IL-1ß production in macrophages. Although ESE inhibited NF-κB activation, it did not affect the IκBα phosphorylation and degradation and the NF-κB p65 nuclear translocation. The result of EMSA revealed that ESE inhibited the NF-κB p65-DNA binding activity. Additionally, ESE also decreased the proinflammatory cytokines in serum and peritoneal lavage fluid of LPS-induced endotoxemic mice. CONCLUSION: ESE has a potently anti-inflammatory effect through inhibiting the NF-κB p65-DNA binding activity in LPS-activated macrophages.

Asymmetric Total Synthesis of Pre-schisanartanin C.

Pre-schisanartanin C belongs to the family of Schisandra nortriterpenoids with potent antihepatitis, antitumor, and anti-HIV activities. This paper presents the enantioselective total synthesis of pre-schisanartanin C (1). An important step in the total synthesis of 1 is gold-catalyzed intramolecular cyclopropanation of a 1,8-enyne substrate bearing a secondary ester group at the propargylic position to prepare a bicyclo[6.1.0]nonane core. Additional highlights include (i) an asymmetric Diels-Alder reaction to install the initial C5 stereogenic center of 1 and (ii) a sequential Pd-catalyzed Stille coupling, regio- and stereoselective Sharpless asymmetric dihydroxylation, and a subsequent intramolecular lactonization to construct the side chain of 1. The developed chemistry paves the way for the total syntheses of other family members bearing highly rigid bicyclo[6.1.0]nonane cores.

[Inhibition and Remediation of Methylmercury Contaminated Soil by Use of Modified Montmorillonite].

Montmorillonite was modified by 3-mercaptopyl trimethoxysilane and chitosan. The modified montmorillonite was characterized by XRD technology. The effects of thiol montmorillonite and chitosan montmorillonite on the inhibition and remediation of methylmercury contaminated soil under different water conditions were studied using laboratory simulation. XRD results showed that both thiol and chitosan were successfully loaded on the montmorillonite. The results of simulation tests showed that the addition of the remediation material to soil contaminated with methylmercury produced a better remediation effect. Compared with the blank control, the content of methylmercury in the soil was reduced by 82.10% (thiol montmorillonite) and 45.20% (chitosan montmorillonite), respectively, in the flooded condition. Under dry/wet alternation, the content of methyl mercury in soil decreased by 66.70% (thiol montmorillonite) and 49.79% (chitosan montmorillonite), respectively. Under drought conditions, the content of methylmercury in soil decreased by 44.66% (thiol montmorillonite), and the concentration of methylmercury in soil decreased by 54.37% after adding chitosan montmorillonite for 4 weeks. Compared with single modified montmorillonite, the repair effect of combined modified montmorillonite and lime treatment was not improved significantly.

Canscora lucidissima, a Chinese folk medicine, exerts anti-inflammatory activities by inhibiting the phosphorylation of ERK1/2 in LPS-activated macrophages.

BACKGROUND: Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. However, the underlying mechanism of its anti-inflammatory effect is not fully understood. METHODS: In this study, we investigated the anti-inflammatory mechanism of ethanol extract of C. lucidissima (Cl-EE) in lipopolysaccharide (LPS)-induced inflammatory models. ELISA, real-time PCR, Western blot and luciferase reporter assay were used for the experiments in vitro, and ICR mouse endotoxemia model was used for in vivo test. RESULTS: Our data showed that Cl-EE reduced the production of NO by down-regulating the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 cells. Meanwhile, it potently decreased other proinflammatory mediators, such as TNF-α, IL-6, MCP-1 and IL-1ß at the transcriptional and translational levels. Further study indicated that Cl-EE did not affect NF-κB signaling pathway but significantly suppressed the phosphorylation of ERK1/2, rather than JNK or p38. In a LPS-induced endotoxemia mouse model, a single intraperitoneal injection of Cl-EE (75-300 mg/kg) could lower circulatory TNF-α, IL-6 and MCP-1 levels. CONCLUSIONS: Collectively, our results indicated that Cl-EE suppressed the phosphorylation level of ERK1/2 thus reducing the transcription and translation of inflammatory genes, thereby exerted anti-inflammatory activity. This study reveals the anti-inflammatory mechanism of C. lucidissima and may provide an effective treatment option for a variety of inflammatory diseases.

Shuang-Huang-Lian Attenuates Airway Hyperresponsiveness and Inflammation in a Shrimp Protein-Induced Murine Asthma Model.

Shuang-Huang-Lian (SHL), an herbal formula of traditional Chinese medicine, is clinically used for bronchial asthma treatment. Our previous study found that SHL prevented basophil activation to suppress Th2 immunity and stabilized mast cells through activating its mitochondrial calcium uniporter. Sporadic clinical reports that SHL was used for the treatment of bronchial asthma can be found. Thus, in this study, we systematically investigated the effects of SHL on asthmatic responses using a shrimp protein (SP)- induced mouse model. SHL significantly inhibited airway inspiratory and expiratory resistance, and histological studies suggested it reduced thickness of airway smooth muscle and infiltration of inflammation cells. It also could alleviate eosinophilic airway inflammation (EAI), including reducing the number of eosinophils and decreasing eotaxin and eosinophil peroxidase levels in the bronchoalveolar lavage fluid (BALF). Further studies indicated that SHL suppressed SP-elevated mouse mast cell protease-1 and IgE levels, prevented Th2 differentiation in mediastinal lymph nodes, and lowered Th2 cytokine (e.g., IL-4, IL-5, and IL-13) production in BALF. In conclusion, SHL attenuates airway hyperresponsiveness and EAI mainly via the inhibition of mast cell activation and Th2 immunity, which may help to elucidate the underlying mechanism of SHL on asthma treatment and support its clinical use.