Fine particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) is a serious air pollutant associated with health problems. Macrophages play an important role in the process of ...PM2.5-induced inflammation in respiratory diseases. However, the detailed mechanism remains unclear. We aimed to examine the mechanism of PM2.5-induced inflammation and find possible anti-inflammatory inhibitors. PM2.5 was collected in Hangzhou, China, and the composition of adsorbed materials on PM2.5 was characterized. RAW 254.7 cells were then treated with PM2.5. Phagocytosis was observed, and inflammatory response was triggered as demonstrated by the release of high levels of monocyte chemoattractant protein-1(MCP-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and increased mRNA expression of inducible nitric oxide synthase (iNOS) and TNF-α. Treatment with classic inhibitors suppressed the released pro-inflammatory factors in a dose-dependent manner. Using Immunology Inflammation Compound Library, we screened 70 inhibitors and clustered them based on similarities in their inhibitory effects, which we detected using cytometric bead array (CBA) assay. Molecular analysis revealed that the expression of toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB), and cyclooxygenase-2 (COX-2) was increased in PM2.5-stimulated RAW 254.7 cells. Corresponding inhibitors were selected, and the CBA assay verified their anti-inflammatory effects. These inhibitors reduced the expression of pro-inflammatory factors, and this reduction was correlated with the downregulation of the TLR4/NF-κB/COX-2 signaling pathway. In conclusion, PM2.5 induces an inflammatory response in macrophages
via
activation of TLR4/NF-κB/COX-2 signaling, and the inhibitors of this pathway are potential therapeutic candidates to treat inflammatory disorders.
Abstract
Numerous studies have demonstrated that endothelial cell senescence plays a decisive role in the development and progression of cardiovascular diseases (CVD). Our previous results confirmed ...that Tetrahydroxy stilbene glycoside (TSG) can alleviate the human umbilical vein endothelial cells (HUVECs) senescence induced by H
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through SIRT1. It has been reported that miR-34a is a translational suppressor of SIRT1. In this study, we aimed to explore whether TSG regulates SIRT1 through miR-34a to ameliorate HUVECs senescence. H
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was used to induce premature senescence in HUVECs, and miR-34a mimic or inhibitor were transfected to over-express or suppress the expression level of miR-34a. Results revealed that TSG apparently decreased the miR-34a expression level in H
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-induced premature senescence of HUVECs. When SIRT1 expression was inhibited by EX527, the attenuation of TSG on the expression level of miR-34a were abolished. When miR-34a expression was knockdown, the effect of TSG on HUVECs senescence could be enhanced. While miR-34a mimic could reverse the effect of TSG on HUVECs senescence. In conclusion, we demonstrated that TSG could attenuated endothelial cell senescence by targeting miR-34a/SIRT1 pathway.
Ethanol extract of
has remarkable anti-inflammatory and anti-pulmonary fibrosis activities in the rat silicosis model. However, its active substances and molecular mechanism are still unclear. To ...uncover the active ingredients and potential molecular mechanism of the
extract, the lipopolysaccharide (LPS)-induced macrophage inflammation model and phospho antibody array were used. Coelonin, a dihydrophenanthrene compound was isolated and identified. It significantly inhibited LPS-induced interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression at 2.5 μg/mL. The microarray data indicate that the phosphorylation levels of 32 proteins in the coelonin pre-treated group were significantly down-regulated. In particular, the phosphorylation levels of the key inflammatory regulators factor nuclear factor-kappa B (NF-κB) were significantly reduced, and the negative regulator phosphatase and tensin homologue on chromosome ten (PTEN) was reduced. Moreover, the phosphorylation level of cyclin dependent kinase inhibitor 1B (p27
), another downstream molecule regulated by PTEN was also reduced significantly. Western blot and confocal microscopy results confirmed that coelonin inhibited LPS-induced PTEN phosphorylation in a dose-dependent manner, then inhibited NF-κB activation and p27
degradation by regulating the phosphatidylinositol-3-kinases/ v-akt murine thymoma viral oncogene homolog (PI3K/AKT) pathway negatively. However, PTEN inhibitor co-treatment analysis indicated that the inhibition of IL-1β, IL-6 and TNF-α expression by coelonin was independent of PTEN, whereas the inhibition of p27
degradation resulted in cell-cycle arrest in the G1 phase, which was dependent on PTEN. The anti-inflammatory activity of coelonin in vivo, which is one of the main active ingredients of
, deserves further study.
Background/Aims: Renal tubulointerstitial fibrosis is the most common pathway of progressive kidney injury, leading to end-stage renal disease. At present, no effective prophylactic treatment method ...is available. This study investigated the anti-fibrotic effects of total flavonoids (TFs) extracted from leaves of Carya Cathayensis in vivo and in vitro, and explored the underlying mechanisms. Methods: Anti-fibrotic effects of TFs were measured using a mouse model of unilateral ureteral obstruction (UUO) and in transforming growth factor-β1 (TGF-β1)-treated mouse tubular epithelial cells (mTECs). mRNA expression and protein levels of Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) were also tested by real-time reverse transcription PCR and western blot analysis. To elucidate the underlying mechanisms, expression of miR-21 was examined in mTECs treated with TFs using miR-21 mimics transfected into mTECs before TGF-β1 and TFs treatment. Regulation of mothers against decapentaplegic homolog (Smad) signaling by miR-21 was subsequently validated via overexpression and deletion of miR-21 followed by a luciferase assay. Results: TFs treatment attenuated renal fibrosis, and inhibited expression of collagens and α-SMA in the kidneys of mice subjected to UUO. In vitro, the TFs significantly decreased expression of fibrotic markers in TGF-β1-treated mTECs. Moreover, TFs reduced miR-21 expression in a time- and dose-dependent manner in mTECs, increased expression of Smad7, and decreased phosphorylation of Smad3. Treatment with miR-21 mimics abolished the anti-fibrotic effects of the TFs on the TGF-β1-treated mTECs. In addition, genetic deletion of miR-21 upregulated expression of Smad7 and suppressed phosphorylation of Smad3, attenuating renal fibrosis in mice. Bioinformatics predictions revealed the potential binding site of miR-21 in the 3′-untranslated region of Smad7, and this was further confirmed by the luciferase assay. Conclusion: TFs ameliorate renal fibrosis via a miR-21/Smad7 signaling pathway, indicating a potential therapy for the prevention of renal fibrosis.
The aim of the present study was to investigate the protective effect of the total flavonoids (TFs) from the leaves of Carya cathayensis Sarg. against early development of atherosclerosis. An in vivo ...model of carotid arterial partial ligation was established in mice, and the effects of TFs were investigated by morphometric measurements, Cell proliferation measurement and immunohistochemistry. The results showed that TFs could reduce neointima area by 41%, and the adventitial thickening induced by partial ligation was remarkable inhibited by TFs treatment. medial SMCs proliferation was significantly inhibited in TFs treated group. Immunohistochemistry analyses demonstrated that mice with TFs treatment have significant less macrophages accumulation in adventitia. These findings indicated that TFs have inhibitory effect in early atherosclerosis lesion formation model and strong action on reduce the inflammation in vivo.
Schematic diagram of multifunctional composite sponge preparation and their properties.
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•Ethanol extract and polysaccharide of Bletilla striata were complementarily mixed.•Ethanol ...extract of B. striata improved antibacterial and anti-inflammatory properties.•The multifunctional sponge exhibited excellent biodegradability and biocompatibility.•An efficient freeze-drying process was adopted to reduce the cost of wound dressing.
Development of a fully functional dressing that can be applied throughout wound healing remains challenging. In this study, Bletilla striata polysaccharide (BSP) and the ethanol extract of B. striata (EEB) were physically blended and vacuum freeze-dried into a new medical dressing with various functions, such as hemostasis, anti-inflammatory, antibacterial and wound healing promotion. The in vivo and in vitro blood coagulation evaluation results showed that the most obvious hemostasis effects coming from the EEB25 sponge was probably due to good water absorption capacity. The drug sensitivity test results showed that the sponges presented a good antibacterial effect originated from the addition of EEB. In addition, the EEB25 sponge showed significant anti-inflammatory effects, as well as excellent biodegradability and biocompatibility. The full-thickness wound experiment illustrated the wound healing rates of EEB25 group on the 8th day and 16th day was 82.76 ± 2.78% and 95.36 ± 3.72%, respectively, which showed significant differences (p < 0.05) in comparison to the model group. Histological observations showed that the EEB25 group formed dense collagen fibers, granulation tissue and numerous new blood vessels on the 16th day, with the skin basically cured. Therefore, BSP/EEB multifunctional composite sponge provided a new perspective for the safe application of wound dressings.
Thermal processing is one of the important techniques for most of the plant-based food and herb medicines before consumption and application in order to meet the specific requirement. The plant and ...herbs are rich in amino acids and reducing sugars, and thermal processing may lead to Maillard reaction, resulting as a high risk of acrylamide pollution. Acrylamide, an organic pollutant that can be absorbed by the body through the respiratory tract, digestive tract, skin and mucous membranes, has potential carcinogenicity, neurological, genetic, reproductive and developmental toxicity. Therefore, it is significant to conduct pollution determination and risk assessment for quality assurance and security of medication. This review demonstrates state-of-the-art research of acrylamide focusing on the toxicity, formation, contamination, determination, and mitigation in taking food and herb medicine, to provide reference for scientific processing and ensure the security of consumers.
•Thermal processing generates high level of acrylamide in various plant-based food.•Dietary exposure to acrylamide leads to considerable health risk in many countries.•Thermally processed herbal medicines have high acrylamide content and health risk.•Efforts are needed to the development of determination and mitigation technology.
Salvianolic acid C (SAC) is a major bioactive component of
(Danshen), a Chinese herb for treating ischemic stroke (IS). However, the mechanism by which SAC affects the IS has not yet been evaluated, ...thus a network pharmacology integrated molecular docking strategy was performed to systematically evaluate its pharmacological mechanisms, which were further validated in rats with cerebral ischemia. A total of 361 potential SAC-related targets were predicted by SwissTargetPrediction and PharmMapper, and a total of 443 IS-related targets were obtained from DisGeNET, DrugBank, OMIM, and Therapeutic Target database (TTD) databases. SAC-related targets were hit by the 60 targets associated with IS. By Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment combined with the protein-protein interaction (PPI) network and cytoHubba plug-ins, nine related signaling pathways (proteoglycans in cancer, pathways in cancer, PI3K-Akt signaling pathway, Focal adhesion, etc.), and 20 hub genes were identified. Consequently, molecular docking indicated that SAC may interact with the nine targets (F2, MMP7, KDR, IGF1, REN, PPARG, PLG, ACE and MMP1). Four of the target proteins (VEGFR2, MMP1, PPARγ and IGF1) were verified using western blot. This study comprehensively analyzed pathways and targets related to the treatment of IS by SAC. The results of western blot also confirmed that the SAC against IS is mainly related to anti-inflammatory and angiogenesis, which provides a reference for us to find and explore the effective anti-IS drugs.
Triclosan (TCS) is a broad-spectrum antibacterial chemical widely presents in people's daily lives. Epidemiological studies have revealed that TCS exposure may affect female puberty development. ...However, the developmental toxicity after low-dose TCS continuous exposure remains to be confirmed. In our study, 8-week-old ICR female mice were continuously exposed to TCS (30, 300, 3000 μg/kg/day) or vehicle (corn oil) from 2 weeks before mating to postnatal day 21 (PND 21) of F1 female mice, while F1 female mice were treated with TCS intragastric administration from PND 22 until PND 56. Vaginal opening (VO) observation, hypothalamic-pituitary-ovarian (HPO) axis related hormones and genes detection, and ovarian transcriptome analysis were carried out to investigate the effects of TCS exposure on puberty onset. Meanwhile, human granulosa-like tumor cell lines (KGN cells) were exposed to TCS to further explore the biological mechanism of the ovary in vitro. The results showed that long-term exposure to low-dose TCS led to approximately a 3-day earlier puberty onset in F1 female mice. Moreover, TCS up-regulated the secretion of estradiol (E
) and the expression of ovarian steroidogenesis genes. Notably, ovarian transcriptomes analysis as well as bidirectional validation in KGN cells suggested that L-type calcium channels and Pik3cd were involved in TCS-induced up-regulation of ovarian-related hormones and genes. In conclusion, our study demonstrated that TCS interfered with L-type calcium channels and activated Pik3cd to up-regulate the expression of ovarian steroidogenesis and related genes, thereby inducing the earlier puberty onset in F1 female mice.
Mounting evidence supports that long-term exposure to fine particle pollutants (PM2.5) is closely implicated in cardiovascular diseases, especially atherosclerosis. Amygdalin is reported to attenuate ...external stimuli-induced cardiovascular diseases. However, the underlying mechanisms are still not understood. In this study, we aim to explore the protective effects of amygdalin on PM2.5-induced human umbilical vein endothelial cell (HUVEC) injury and unravel the specific mechanisms by MTT, DCFH-DA, biochemical, immunofluorescence, ELISA, RT-qPCR, flow cytometry, TUNEL and western blot analysis. The results reveal that amygdalin reverses PM2.5-induced cytotoxicity and attenuates intracellular ROS production. Moreover, amygdalin increases the levels of SOD and GSH and alleviates the MDA content. Additionally, amygdalin causes a decline of IL-6, IL-1β, TNF-α and COX-2 levels. Moreover, amygdalin inhibits NF-κB p50 and TLR4 protein expressions and NF-κB p65 nuclear translocation. Concomitantly, a decline of phospho-NF-κB p65/NF-κB p65 and phospho-IκB-α/IκB-α is detected. Meanwhile, amygdalin pretreatment reduces HUVEC apoptosis. In addition, amygdalin triggers an upregulation of Bcl-2 and a downregulation of Bax after stimulation with PM2.5. Collectively, these results suggest that amygdalin suppresses PM2.5-induced HUVEC injury by regulating the TLR4/NF-κB and Bcl-2/Bax signaling pathways, indicating that amygdalin may be a novel target for atherosclerosis treatments.
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