China's economy has flourished since reform and opening up. At the same time, China's ability to attract foreign investment in the world continued to increase. However, with the rapid development of ...the economy, China's energy crisis and environmental pollution have been continuously deepened, exposing increasingly serious problems in the energy consumption structure. As a critical mean to address the environmental problems and achieve sustainable development, the production and utilization of renewable energy resources is particularly critical. This paper aims to investigate the relationship amongst renewable energy consumption, foreign direct investment and gross domestic product in 31 Chinese provinces from 2000 to 2015. Specifically, the unit root test, cointegration test, vector error-correction model, impulse response function analysis, and Granger causality test are employed for the estimations. The empirical results indicate that there is a long-term and stable equilibrium relationship between gross domestic product per capita, foreign direct investment per capita, and renewable energy consumption per capita. Additionally, in the short term, foreign direct investment cannot significantly cause renewable energy consumption change; but in the long run, a modest slowdown in gross domestic product growth and targeted foreign direct investment will generate a significant boost on renewable energy in China.
•Relationship amongst renewable energy consumption, GDP and FDI in China is examined.•Vector error correction model and fully modified ordinary least squares are employed.•Long-run equilibrium exists between renewable energy consumption, GDP and FDI.•There is unilateral causality from GDP and FDI to renewable energy consumption in the long run.•FDI cannot significantly cause renewable energy consumption change in the short term.
Naringenin, a flavonoid compound which exists abundantly in Citrus fruits, is proven to possess excellent antitussive and expectorant effects. However, the clinical applications of naringenin are ...restricted by its poor solubility and low local concentration by oral administration. The aim of the present study is to prepare a naringenin-hydroxypropyl-β-cyclodextrin (naringenin-HPβCD) inclusion as an inhalation solution for pulmonary delivery. The naringenin-HPβCD inclusion was characterized by phase solubility study, XRD, differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1HNMR), and two-dimensional rotating frame Overhauser effect spectroscopy (2D ROESY). The in vitro permeability of the inclusion was evaluated on Calu-3 cells and the pharmacokinetic profile of pulmonary delivery was investigated in Sprague-Dawley (SD) rats. Based on the linear model of phase solubility study, the relationship between naringenin and HPβCD was identified as AL type with a 1:1 stoichiometry. XRD, DSC, and NMR studies indicated that the entire naringenin molecule is encapsulated into the cavity of HPβCD. HPβCD could increase the concentration of naringenin in the epithelium-lining fluid (ELF) of Calu-3 cells and act as a sustained release system for naringenin. The pharmacokinetic profile of naringenin-HPβCD inclusion showed rapid response and higher local concentration by pulmonary delivery. In conclusion, pulmonary delivery of naringenin-HPβCD inclusion is a promising formulation strategy, which could provide a new possibility for the clinical application of naringenin.
Extracellular vesicles (EVs)-mediated epithelium-macrophage crosstalk has been proved to maintain lung homeostasis in cigarette smoke-induced lung diseases such as chronic obstructive pulmonary ...disease (COPD). In our previous study, we found that EVs derived from cigarette smoke extract (CSE) treated BEAS-2B promoted M1 macrophage polarization, which probably accelerated the development of inflammatory responses. Naringenin has been proved to suppress M1 macrophage polarization, but whether naringenin regulates macrophage polarization mediated by EVs has not been reported. In this study, we firstly found that EVs derived from naringenin and CSE co-treated BEAS-2B significantly inhibited the expression of CD86 and CD80 and the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase (iNOS), and IL-12 in macrophage induced by EVs derived from CSE-treated BEAS-2B. Further research revealed that naringenin downregulated BEAS-2B-derived EVs miR-21-3p which targeted phosphatase and tensin homolog deleted on chromosome ten/protein kinase B (PTEN/AKT) cascade in macrophages and then suppressed M1 macrophage polarization. Subsequent proteomics suggested that naringenin decreased BEAS-2B-derived EVs poly ADP-ribose polymerase (PARP)1 expression thereby suppressing M1 macrophage polarization probably. Our study provides novel pharmacological references for the mechanism of naringenin in the treatment of cigarette smoke-induced lung inflammatory diseases.
Naringenin is found mainly in citrus fruits, and is thought to be beneficial in the prevention and control of lung diseases. This study aims to investigate the mechanisms of naringenin against the ...damage in the lung caused by cigarette smoke. A system bioinformatic approach was proposed to predict the mechanisms of naringenin for protecting lung health. Then, we validated this prediction in BEAS-2B cells treated with cigarette smoke extract (CSE). System bioinformatic analysis indicated that naringenin exhibits protective effects on lung through the inhibition of inflammation and suppression of oxidative stress based on a multi-pathways network, mainly including oxidative stress pathway, Nrf2 pathway, Lung fibrosis pathway, IL-3 signaling pathway, and Aryl hydrocarbon receptor pathway. The in vitro results showed that naringenin significantly attenuated CSE-induced up-regulation of IL-8 and TNF-α. CSE stimulation increased the mRNA expressions of Nrf2, HO-1, and NQO1; the levels of total protein and nuclear protein of Nrf2; and the activity of SOD on days 2 and 4; but decreased these indexes on day 6. Naringenin can balance the antioxidant system by regulating Nrf2 and its downstream genes, preliminarily validating that Nrf2 pathway is involved in the protection offered by naringenin against cigarette smoke-induced damage to the lung. It suggests that dietary naringenin shows possible potential use in the management of lung health.
Sleep disorders were associated with oral health. Inflammation has especially been thought to be a key factor in linking oral diseases and sleep deficiency. However, how chronic sleep deprivation ...(CSD) affects oral homeostasis, particularly oral inflammation and oral microbiota, is still unknown. This study aimed to uncover the systematic relationship between oral homeostasis and CSD in rats. The metabolomics in serum, proteomics in the tongue tissues, and microbiome analysis in the oral cavity in CSD rats were performed. Multi-omics data integration analysis was performed to uncover the systematic relationship between oral homeostasis and CSD through the weighted correlation network analysis. We found that CSD could lead to oral inflammation in rats. CSD significantly increased systemic inflammation by enhancing the serum levels of IL-1β, IL-6 and inhibiting the serum level of IL-10. Serum levels of adrenocorticotropin hormone, corticosterone, and triiodothyronine were increased in CSD rats, and the steroid hormone biosynthesis pathway was also found to be involved in the perturbation resulting from CSD, together suggesting the activation of the hypothalamic-pituitary-adrenocortical and hypothalamic-pituitary-thyroid axis. CSD led to changes of oral microbiota composition, and g_
,
, and g_
were significantly correlated with multiple proteins in bacterial invasion of epithelial cells pathway, which may partially responsible for oral inflammation resulting from CSD. The changes of proteomic profiling expression caused by CSD in tongue tissues were mainly enriched in neurodegenerative diseases pathways and immune/inflammation-related pathways. Multi-omics analysis indicated that the inflammatory response-related modules were significantly correlated with the neurodegenerative disease-related module suggesting a possible link between neurodegenerative diseases and oral inflammation. Together, CSD induced oral inflammation and subtle changes on oral microbiota. Our study is helpful to further understand the role that oral homeostasis plays in the process by which CSD affects human health and disease.
Naringenin, a natural flavonoid widely found in citrus fruits, has been reported to possess anti-oxidant, anti-inflammatory, and hepatoprotective properties as a natural dietary supplement. However, ...the regulatory mechanism of naringenin in human liver remains unclear. In the present study, messenger RNA sequencing (mRNA-seq), microRNA sequencing (miRNA-seq), and real-time qPCR were used to distinguish the expression differences between control and naringenin-treated HepaRG cells. We obtained 1037 differentially expressed mRNAs and 234 miRNAs. According to the target prediction and integration analysis in silico, we found 20 potential miRNA-mRNA pairs involved in liver metabolism. This study is the first to provide a perspective of miRNA-mRNA interactions in the regulation of naringenin via an integrated analysis of mRNA-seq and miRNA-seq in HepaRG cells, which further characterizes the nutraceutical value of naringenin as a food additive.
Oral ulcers are the most prevalent oral mucosal diseases globally, and no specific treatment schemes are currently available due to the complexity of oral ulcer diseases. Sleep deprivation increases ...the risk of a deterioration in oral health. Kouyanqing Granule (KYQG) has been used for decades in China to treat inflammatory diseases of the mouth and throat associated with the hyperactivity of fire due to yin deficiency syndrome. However, the mechanisms underlying the effects of KYQG in the treatment of oral ulcers are still unclear. The aims of this study were to investigate whether KYQG treatment could attenuate the symptoms of oral ulcers worsened by sleep deprivation and identify the involved metabolic pathways. First, we conducted chemical profiling of KYQG
via
UPLC–MS analysis. We then combined pharmacological and metabolomics approaches in a phenol-induced rat model of oral ulcers worsened by sleep deprivation. A total of 79 compounds were initially identified. Our observations showed that KYQG treatment induced a significantly higher healing rate in oral ulcers worsened by sleep deprivation. KYQG significantly reduced the levels of 5-HT and GABA in serum, and only decreased the 5-HT level in brain tissue after phenol injury followed by sleep deprivation. Moreover, KYQG administration significantly suppressed systemic inflammation by inhibiting TNF-α, IL-1β, IL-6, IL-18, and MCP-1. Immunohistochemical analysis further revealed that KYQG inhibited IL-6 expression in buccal mucosa tissues. KYQG treatment also significantly decreased the serum levels of ACTH, CORT, IgM, and 8-OHdG. Serum metabolomics analysis showed that a total of 30 metabolites showed significant differential abundances under KYQG intervention, while metabolic pathway analysis suggested that the altered metabolites were associated with the dysregulation of eight metabolic pathways. Taken together, our results indicated that KYQG attenuates the symptoms of oral ulcers worsened by sleep deprivation probably through the regulation of the neuroimmunoendocrine system, oxidative stress levels, and tryptophan metabolism. This study also provides a novel approach for addressing the increased health risks resulting from sleep deficiency using an herbal medicine formula.
With the wide application of silver nanoparticles (AgNPs), their potential damage to human health needs to be investigated. Lung is one of the main target organs after inhalation of AgNPs. Naringenin ...has been reported to have anti-inflammatory and anti-oxidative properties. This study aims to evaluate the protective effects of naringenin against AgNPs-induced lung injury and determine the underlying mechanism. In in vivo experiments, AgNPs were intratracheally instilled into ICR mice (l mg/kg) to establish a lung injury model. These mice were then treated with naringenin by oral gavage (25, 50, 100 mg/kg) for three days. Naringenin treatment decreased the levels of white blood cells, neutrophils, and lymphocytes in the blood, ameliorated lung injury, suppressed the release of pro-inflammatory cytokines, normalized ferroptotic markers and prevented oxidative stress with elevating Nrf2 and HO-1 protein expressions in lung. In in vitro experiments, BEAS-2B cells were firstly treated with AgNPs (320 μg/mL) and then naringenin (25, 50, and 100 μM), respectively. Naringenin attenuated AgNPs-induced oxidative stress and inflammatory response. Moreover, naringenin attenuated AgNPs-induced apoptosis with modulated low BAX, CytC, cleaved Caspase9, cleaved Caspase3 but high Bcl2. Furthermore, naringenin effectively decreased ferroptotic markers and increased the protein expressions of Nrf2 and HO-1, as well as increased the nuclear translocation of Nrf2. Importantly, the anti-apoptotic and anti-ferroptotic effects of naringenin in BEAS-2B cells were found to be at least partially Nrf2-dependent. These results indicated that naringenin exerted anti-inflammation, anti-apoptosis, and anti-ferroptosis effects and protected against AgNPs-induced lung injury at least partly via activating Nrf2/HO-1 signaling pathway.
Inhalation of cigarette smoke induces airway and parenchyma inflammation that predisposes smokers to multiple lung diseases such as COPD. Macrophage polarization, an important specifying feature of ...inflammation, is involved in the progression of pulmonary inflammation. Exosomes and their loaded miRNAs provide a medium for cross-talk between alveolar macrophages and lung epithelial cells to maintain lung homeostasis. In this study, we treated Beas-2B with CSE to speculate the effects of Beas-2B-derived exosomes on macrophage polarization and performed exosomal miRNAomics analysis to explore the mechanism. We found that CSE-treated Beas-2B-derived exosomes could not only increase the percentages of CD86+, CD80+ CD163+, and CD206+ cells but also induce the secretion of TNF-α, IL-6, iNOS, IL-10, Arg-1, and TGF-β, indicating both M1 and M2 polarization of RAW264.7 macrophages were promoting. We performed miRNAomics analysis to identify 27 differentially expressed exosomal miRNAs such as miR-29a-3p and miR-1307-5p. Next, we obtained 14942 target genes of these miRNAs such as SCN1A and PLEKHA1 through the prediction of TargetScan and miRanda. We utilized KEGG enrichment analysis for these targets to identify potential pathways such as the PI3K-Akt signaling pathway and the MAPK signaling pathway on the regulation of macrophage polarization. We further found that miR-21-3p or miR-27b-3p may play critical roles in the promotion of CSE-Exo on macrophage polarization by miRNA interference. Collectively, this study provided novel information for diagnostic and therapeutic tactics of cigarette smoke-related lung diseases.
•CSE-treated Beas-2B-derived exosomes promoted both M1 and M2 macrophage polarization.•We identified 27 differentially expressed exosomal miRNAs by miRNAomics analysis.•We obtained 14942 target genes of these miRNAs from TargetScan and miRanda.•We performed KEGG analysis for these targets to identify potential signaling pathways.•miR-21-3p and miR-27b-3p may play critical roles in the promotion of polarization.
Alveolar macrophages are one of the momentous regulators in pulmonary inflammatory responses, which can secrete extracellular vesicles (EVs) packing miRNAs. Ferroptosis, an iron-dependent cell death, ...is associated with cigarette smoke-induced lung injury, and EVs have been reported to regulate ferroptosis by transporting intracellular iron. However, the regulatory mechanism of alveolar macrophage-derived EVs has not been clearly illuminated in smoking-related pulmonary ferroptosis. Despite the known anti-ferroptosis effects of naringenin in lung injury, whether naringenin controls EVs-mediated ferroptosis has not yet been explored.
We explore the effects of EVs from cigarette smoke-stimulated alveolar macrophages in lung epithelial ferroptosis, and elucidate the EV miRNA-mediated pharmacological mechanism of naringenin.
Differential and ultracentrifugation were conducted to extract EVs from different alveolar macrophages treatment groups in vitro. Both intratracheal instilled mice and treated epithelial cells were used to investigate the roles of EVs from alveolar macrophages involved in ferroptosis. Small RNA sequencing analysis was performed to distinguish altered miRNAs in EVs. The ferroptotic effects of EV miRNAs were examined by applying dual-Luciferase reporter assay and miRNA inhibitor transfection experiment.
Here, we firstly reported that EVs from cigarette smoke extract-induced alveolar macrophages (CSE-EVs) provoked pulmonary epithelial ferroptosis. The ferroptosis inhibitor ferrostatin-1 treatment reversed these changes in vitro. Moreover, EVs from naringenin and CSE co-treated alveolar macrophages (CSE+Naringenin-EVs) markedly attenuated the lung epithelial ferroptosis compared with CSE-EVs. Notably, we identified miR-23a-3p as the most dramatically changed miRNA among Normal-EVs, CSE-EVs, and CSE+Naringenin-EVs. Further experimental investigation showed that ACSL4, a pro-ferroptotic gene leading to lipid peroxidation, was negatively regulated by miR-23a-3p. The inhibition of miR-23a-3p diminished the efficacy of CSE+Naringenin-EVs.
Our findings firstly provided evidence that naringenin elevated the EV miR-23a-3p level from CSE-induced alveolar macrophages, thereby inhibiting the mouse lung epithelial ferroptosis via targeting ACSL4, and further complemented the mechanism of cigarette-induced lung injury and the protection of naringenin in a paracrine manner. The administration of miR-23a-3p-enriched EVs has the potential to ameliorate pulmonary ferroptosis.
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