Background and Purpose
Regulating macrophage–hepatocyte crosstalk through P2X7 receptors has led to new pharmacological strategies to reverse alcoholic hepatosteatosis. We investigated how ...tetrahydroxystilbene glucoside (2354glu), isolated from Polygonum multiflorum, modulates macrophage–hepatocyte crosstalk during alcoholic hepatosteatosis.
Experimental Approach
A model of alcoholic hepatosteatosis was established by giving ethanol intragastrically to C57BL/6 mice. HepG2 cells were incubated in conditioned medium from LPS+ATP‐activated THP‐1 human macrophages with silenced or overexpressed P2X7 receptors. THP‐1 macrophages or mouse peritoneal macrophages were pretreated with 2354glu for 1 hr prior to LPS+ATP stimulation. Western blots, RT‐PCR and immunohistochemical analysis were used, along with over‐expression and silencing of P2X7 receptors.
Key Results
Knockdown or overexpression of P2X7 receptors in THP‐1 macrophages affected release of mature IL‐1β and, subsequently, modulated lipid metabolism in HepG2 cells via the LKB–AMPK pathway. 2354glu ameliorated alcoholic hepatosteatosis in mice by regulating LKB1–AMPK–SREBP1 pathway and its target genes. Suppression of P2X7 receptor activation by 2354glu inhibited IL‐1β release and reduced macrophage and neutrophil infiltration. In macrophages stimulated with LPS+ATP, expression of P2X7 receptors, caspase‐1 and NF‐κB, release of IL‐1β, calcium influx and PI uptake were reduced by 2354glu. SIRT1–LKB1–AMPK–SREBP1 axis‐mediated lipid accumulation in HepG2 cells was reduced when they were cultured with conditioned media from LPS+ATP‐activated THP‐1 macrophages pretreated with 2354glu.
Conclusion and Implications
Modulation of P2X7 receptors in macrophages regulated lipid accumulation in hepatocytes during alcoholic hepatosteatosis. 2354glu might be a promising candidate that targets P2X7 receptors in macrophages interacting with hepatocytes during alcoholic hepatosteatosis.
This article proposes a cognitive radar (CR) framework to improve the performance of the estimation and recognition for range-extended targets. To overcome the angular uncertainty and exploit the ...temporal correlation of target signatures, we introduce the static multimodel approach and the exponential correlation model to describe the dynamics of target signatures. The estimate of target signatures and the probability distribution of target hypotheses are updated recursively in response to the latest echo, ruled by the Bayesian theory. A waveform optimization module is integrated into the framework, which designs the waveform for the next emission according to the knowledge extracted from the echo history. A design criterion based on mutual information (MI) is derived, which implies the average estimation capability for all target hypotheses and the mean between-hypotheses divergence. The proposed method is examined using both synthetic data and electromagnetic (EM) simulation data of realistic targets.
Bilobalide, the only sesquiterpene compound from
leaf, exhibits various beneficial pharmaceutical activities, such as antioxidant, anti-inflammation, and protective effects for the central nervous ...system. Several bioactive components extracted from
extract reportedly have the potential to attenuate lipid metabolism. However, the effect of bilobalide on lipid metabolism remains unclear. In this study, we used 3T3-L1 cells as the cell model to investigate the effect of bilobalide on adipogenesis. The results showed that bilobalide inhibited 3T3-L1 preadipocyte differentiation and intracellular lipid accumulation. Quantitative real-time PCR and western blotting results indicated that several specific adipogenic transcription factors and a few important adipogenesis-related genes were significantly down regulated on both mRNA and protein levels in bilobalide treatment groups. By contrast, the expression of some lipolytic genes, such as adipose triglyceride lipase, hormone-sensitive lipase (
), and carnitine palmitoyltransferase-1α, were all up-regulated by bilobalide treatment, and the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase 1, and HSL were stimulated. Furthermore, bilobalide treatment partially restored AMPK activity following its blockade by compound C (dorsomorphin). These results suggested that bilobalide inhibited adipogenesis and promoted lipolysis in 3T3-L1 cells by activating the AMPK signaling pathway.
Stomata in leaves regulate gas exchange between the plant and its atmosphere. Various environmental stimuli elicit abscisic acid (ABA); ABA leads to phosphoactivation of slow anion channel 1 (SLAC1); ...SLAC1 activity reduces turgor pressure in aperture-defining guard cells; and stomatal closure ensues. We used electrophysiology for functional characterizations of
SLAC1 (
SLAC1) and cryoelectron microscopy (cryo-EM) for structural analysis of
SLAC1 (
SLAC1), at 2.97-Å resolution. We identified 14 phosphorylation sites in
SLAC1 and showed nearly 330-fold channel-activity enhancement with 4 to 6 of these phosphorylated. Seven SLAC1-conserved arginines are poised in
SLAC1 for regulatory interaction with the N-terminal extension. This
SLAC1 structure has its pores closed, in a basal state, spring loaded by phenylalanyl residues in high-energy conformations. SLAC1 phosphorylation fine-tunes an equilibrium between basal and activated SLAC1 trimers, thereby controlling the degree of stomatal opening.
Dienamines formed in situ from a chiral secondary amine and an α,β‐unsaturated aldehyde undergo the highly α‐regioselective title reaction to give densely functionalized piperidine derivatives with ...excellent enantioselectivity (see scheme). The products were converted into a variety of versatile cyclic frameworks. Ts=4‐toluenesulfonyl.
Raising the HOMO: 2,4‐Dienals can react with nitroalkenes in trienamine‐catalyzed asymmetric Diels–Alder reactions (see scheme). Crucial for the success is raising the HOMO energy of the diene ...through the introduction of appropriate substituents. The reaction exhibits unusually high enantioselectivity and exo selectivity; endo addition is possibly disfavored because of the electrostatic repulsion shown in the scheme.
To reveal the mechanism of anti-renal fibrosis effects of an
-butanol extract from
renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an
-butanol extract ...(BUT) from
(Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg
) and BUT-treated (1.75, 1.5 and 1.25 g kg
) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose.
BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.
The excretory-secretory (ES) antigens of Trichinella spiralis muscle larvae (ML) are the most commonly used diagnostic antigens for trichinellosis. Their main disadvantage for the detection of ...anti-Trichinella IgG is false-negative results during the early stage of infection. Additionally, there is an obvious window between clinical symptoms and positive serology.
ELISA with adult worm (AW) ES antigens was used to detect anti-Trichinella IgG in the sera of experimentally infected mice and patients with trichinellosis. The sensitivity and specificity were compared with ELISAs with AW crude antigens and ML ES antigens.
In mice infected with 100 ML, anti-Trichinella IgG were first detected by ELISA with the AW ES antigens, crude antigens and ML ES antigens 8, 12 and 12 days post-infection (dpi), respectively. In mice infected with 500 ML, specific antibodies were first detected by ELISA with the three antigen preparations at 10, 8 and 10 dpi, respectively. The sensitivity of the ELISA with the three antigen preparations for the detection of sera from patients with trichinellosis at 35 dpi was 100%. However, when the patients' sera were collected at 19 dpi, the sensitivities of the ELISAs with the three antigen preparations were 100% (20/20), 100% (20/20) and 75% (15/20), respectively (P < 0.05). The specificities of the ELISAs with the three antigen preparations were 98.11, 95.60 and 89.31%, respectively (P < 0.05).
The sensitivity and specificity of the T. spiralis AW ES antigens were superior to those of the AW crude antigens and ML ES antigens. Thus, the AW ES antigens might serve as potential antigens for the early and specific serodiagnosis of trichinellosis.
The stomatal pores of higher plants enable gaseous exchange into and out of leaves for photosynthesis and evaporation. Stomatal opening is induced by both blue and red lights. It is shown that blue ...light-induced stomatal opening is mediated by the blue light receptor phototropins （PHOT1 and PHOT2） and cryptochromes （CRY1 and CRY2）. However, whether phytochrome B （phyB） is involved in red light regulation of stomatal opening remains largely unclear. Here, we report a positive role for Arabidopsis （Arabidopsis thaliana） phyB in the regulation of red light-induced stomatal opening. The phyB mutant stomata displayed a reduced red light response, whereas stomata of the phyB-overexpressing plants displayed a hypersensitive response to red light. In addition, stomata of the cry1 cry2 phyB, photl phot2 phyB, and cry1 phyA phyB triple mutant plants showed more reduced light response than those of the single or double mutant plants under white light, implying that phyB acts in concert with phyA, CRY, and PHOT in light regulation of stomatal opening. Stomata of phyB cop1 mutant opened less wide than those of the cop1 mutant, and stomata of the pif3 pif4 mutant opened wider than those of the wild-type, indicating that COP1, together with the PIFs （phytochrome interacting factors）, may act downstream of PHYB in regulating stomatal opening. Furthermore, quantitative RT-PCR analysis showed that the expression of MYB60 was reduced in the cry1 cry2 and phyA phyB mutants under blue and red lights, respectively, but induced in the CRY1- and phyB-overexpressing plants. These results demonstrate that phyB and CRY might regulate stomatal opening, at least in part, by regulating MYB60 expression.
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