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•Lung injury and inflammation occurred after SD rats were treated with 0, 0.5, 1 and 2 mg/200 μL 100 nm PS-MPs for 14 days.•Gene sequencing detected a series of altered lncRNA and ...circRNA after treatment of 100 nm PS-MPs in rats.•LncRNA XLOC_031479, lncRNA XLOC_014188, circRNA 014924, circRNA 006,603 and circ 003,982 may be potential targets for lung damage caused by PS-MPs.
Microplastics (MPs) pollution has become a global concern due to its close relation to the environment and human health. Recently, more and more studies have pointed out the existence of MPs in the air, but its potential inhalation toxicity is unclear. Polystyrene Microplastics (PS-MPs) is one of the representative MPs. Besides, non-coding RNA plays crucial roles in regulating gene expression. Therefore, this study aims to provide new insights into the molecular exploration of PS-MPs inhalation. In this study, Sprague Dawley（SD）rats were treated with 100 nm, 500 nm, 1 μm and 2.5 μm PS-MPs for three days. And then intra-tracheal instillation of saline or 100 nm PS-MPs with 0, 0.5, 1 and 2 mg/200 μL were performed in SD rats every two days for two consecutive weeks. The deposition of PS-MPs was observed through immunofluorescence. Lung histological alternations were observed in haematoxylin and eosin (H&E) staining sections. The expressions of pro-inflammatory cytokines were quantified by ELISA and qPCR. Genome-wide transcriptomic profiling of long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) in rats lung were done by ribosomal RNA depleted RNA sequencing and verified by qRT-PCR. We observed that 100 nm and 1 μm PS-MPs could deposite in the lungs. In addition, pathological examination shows alveolar destruction and bronchial epithelium arranged in a mess in PS-MPs groups. Furthermore, the expressions of pro-inflammatory cytokines IL-6, TNF-α and IL-1β were upregulated in PS-MPs exposed rats. Sequencing results showed that 269 circRNAs and 109 lncRNAs were differentially expressed in lung tissue of the saline and PS-MPs exposed rats. The upregulated expressions of lncRNA XLOC_031479, circRNA 014924 and circRNA 006603 and the downregulated expressions of lncRNA XLOC_014188 and circ003982 were identified by qRT-PCR in MPs group. The identified novel circRNAs and lncRNAs may paly important role in the development of lung inflammation caused by PS-MPs.
Aloe vera has been widely used in health and nutritional supplements in Chinese herbal medicine. Furthermore, Aloe vera production has been an emerging industry for making cosmetics and functional ...food. However, the reported adverse effects raised questions as to whether Aloe vera and its products were safe enough to be used in medicine and health care. In view of this, the safety evaluation of Aloe vera products before marketing is very important. The present study aimed to assess the toxicological profile of Aloe vera soft capsule (ASC), through acute, subacute toxicity and genotoxicity tests. Male and female ICR mice were received by oral gavage 15000 mg/kg bodyweight of ASC in the acute toxicity test. Male and female SD rats were fed on diet blended with different doses of ASC (equivalent to 832.5, 1665 and 3330 mg/kg bodyweight of ASC) for the subacute toxicity test. In the acute toxicity study, no mortality or behavioral changes were observed, indicating the LD50 was higher than 15000 mg/kg bodyweight. In the subacute toxicity test, no significant changes were observed in bodyweight, food consumption, hematological, biochemical or histopathological parameters in the rats exposed. These data suggested that ASC used in this study did not produce any marked subacute toxic effects up to a maximum concentration of 3330 mg/kg bodyweight. In the genotoxicity study, ASC showed no mutagenic activity in the Ames test and no evidence of potential to induce bone marrow micronucleus or testicular chromosome aberrations in ICR mice exposed to 10000 mg/kg bodyweight. Collectively, ASC could be considered safe before it was marketed as a laxative and moistening health food.
The avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans. Avian influenza is characterized by pronounced activation of the ...proinflammatory cytokine cascade, which perpetuates the inflammatory response, leading to persistent systemic inflammatory response syndrome and pulmonary infection in animals and humans. There are currently no specific treatment strategies for avian influenza.
We hypothesized that mesenchymal stromal cells (MSCs) would have beneficial effects in the treatment of H9N2 AIV-induced acute lung injury in mice. Six- to 8-week-old C57BL/6 mice were infected intranasally with 1 × 10
MID
of A/HONG KONG/2108/2003 H9N2 (HK) H9N2 virus to induce acute lung injury. After 30 min, syngeneic MSCs were delivered through the caudal vein. Three days after infection, we measured the survival rate, lung weight, arterial blood gas, and cytokines in both bronchoalveolar lavage fluid (BALF) and serum, and assessed pathological changes to the lungs.
MSC administration significantly palliated H9N2 AIV-induced pulmonary inflammation by reducing chemokines and proinflammatory cytokines levels, as well as reducing inflammatory cell recruit into the lungs. Thus, H9N2 AIV-induced lung injury was markedly alleviated in mice treated with MSCs. Lung histopathology and arterial blood gas analysis were improved in mice with H9N2 AIV-induced lung injury following MSC treatment.
MSC treatment significantly reduces H9N2 AIV-induced acute lung injury in mice and is associated with reduced pulmonary inflammation. These results indicate a potential role for MSC therapy in the treatment of clinical avian influenza.
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•1. Emphysema occurred after SD rats were treated with 0, 0.5, 1.0 and 2.0 mg/m3 100 nm polystyrene microplastics (PS-MPs) for 90 days.•2. Extracellular matrix (ECM) degradation in ...macrophages is associated with PS-MPs-induced emphysema.•3. The circRNA_SMG6/miR-570-3p/PTEN axis is involved in regulating macrophage ECM degradation.
Microplastics (MPs) are plastic particles < 5 mm in diameter, of which polystyrene microplastics (PS-MPs) are representative type. The extracellular matrix (ECM) degradation of macrophages is associated with the development of emphysema. Additionally, circular RNAs (circRNAs) have a regulatory role in epigenetic mechanisms related to lung disease. However, the mechanisms of the ECM degradation and circRNAs in MPs-induced emphysema are still unclear. In our study, Sprague-Dawley (SD) rats were treated with 0, 0.5, 1.0 and 2.0 mg/m3 100 nm PS-MPs for 90 days in an inhalation experiment. PS-MPs-exposed rats showed elevated airway resistance and pulmonary dysfunction. Lung histopathology exhibited inflammatory cell infiltration, septal thickening and alveolar dilatation. Exposure to PS-MPs was able to induce elevated levels of ECM degradation-related markers MMP9 and MMP12, as well as reduced levels of elastin in rat lung tissues. CircRNA_SMG6 is a non-coding RNA (ncRNA) with a homologous circular structure in human, rat and mouse. The expression level of circRNA_SMG6 was decreased in both rat lung tissues exposed to PS-MPs and PS-MPs-treated THP-1 cells. The luciferase reporter gene demonstrated that circRNA_SMG6 combined with miR-570-3p and co-regulated PTEN, the target gene of miR-570-3p. Moreover, overexpression of circRNA_SMG6 or inhibition of miR-570-3p attenuated PS-MPs-induced ECM degradation in THP-1 cells. Taken together, circRNA_SMG6 may have a significant function in the deterioration of emphysema caused by PS-MPs-induced macrophage ECM degradation by regulating miR-570-3p. Our findings reveal a novel mechanism of emphysema caused by PS-MPs and provide valuable information for assessing the health risks of MPs.
Advances in nanotechnology depend upon expanding the ability to create new and complex materials with well-defined multidimensional mesoscale structures. The creation of hybrid hierarchical ...structures by combining colloidal organic and inorganic building blocks remains a challenge due to the difficulty in preparing organic structural units of precise size and shape. Here we describe a design strategy to generate controlled hierarchical organic-inorganic hybrid architectures by multistep bottom-up self-assembly. Starting with a suspension of large inorganic nanoparticles, we anchor uniform block copolymer crystallites onto the nanoparticle surface. These colloidally stable multi-component particles can initiate the living growth of uniform cylindrical micelles from their surface, leading to three-dimensional architectures. Structures of greater complexity can be obtained by extending the micelles via addition of a second core-crystalline block copolymer. This controlled growth of polymer micelles from the surface of inorganic particles opens the door to the construction of previously inaccessible colloidal organic-inorganic hybrid structures.
Pyrene derivatives can absorb onto the surface of carbon nanotubes and graphite particles through π−π interactions to functionalize these inorganic building blocks with organic surface moieties. ...Using single molecule force spectroscopy, we have demonstrated the first direct measurement of the interaction between pyrene and a graphite surface. In particular, we have connected a pyrene molecule onto an AFM tip via a flexible poly(ethylene glycol) (PEG) chain to ensure the formation of a molecular bridge. The π−π interaction between pyrene and graphite is thus indicated to be ∼55 pN with no hysteresis between the desorption and adhesion forces.
Background
Health-related quality of life (HRQoL) is a critical aspect of overall well-being for patients with lung cancer, particularly those with metastatic spinal cord compression (MSCC). However, ...there is currently a lack of universal evaluation of HRQoL in this specific patient population. The aim of this study was to develop a nomogram that can accurately predict HRQoL outcomes in patients with lung cancer-related MSCC.
Methods
A total of 119 patients diagnosed with MSCC secondary to lung cancer were prospectively collected for analysis in the study. The least absolute shrinkage and selection operator (LASSO) regression analysis, along with 10-fold cross-validation, was employed to select the most significant variables for inclusion in the nomogram. Discriminative and calibration abilities were assessed using the concordance index (C-index), discrimination slope, calibration plots, and goodness-of-fit tests. Net reclassification index (NRI) and integrated discrimination improvement (IDI) analyses were conducted to compare the nomogram’s performance with and without the consideration of comorbidities.
Results
Four variables were selected to construct the final nomogram, including the Eastern Cooperative Oncology Group (ECOG) score, targeted therapy, anxiety scale, and number of comorbidities. The C-index was 0.87, with a discrimination slope of 0.47, indicating a favorable discriminative ability. Calibration plots and goodness-of-fit tests revealed a high level of consistency between the predicted and observed probabilities of poor HRQoL. The NRI (0.404, 95% CI: 0.074–0.734, p = 0.016) and the IDI (0.035, 95% CI: 0.004–0.066, p = 0.027) confirmed the superior performance of the nomogram with the consideration of comorbidities.
Conclusions
This study develops a prediction nomogram that can assist clinicians in evaluating postoperative HRQoL in patients with lung cancer-related MSCC. This nomogram provides a valuable tool for risk stratification and personalized treatment planning in this specific patient population.
•In vitro combination of FFYH and oseltamivir exhibits better inhibitory effect on influenza A virus than treatment alone.•In vivo combination of FFYH and oseltamivir shows better protective effect ...on lethal influenza A virus infection than treatment alone.•Combination of FFYH and oseltamivir could more effectively inhibit the TLR7/MyD88 signaling pathway than treatment alone.•Combination of FFYH and oseltamivir might comprehensively exert antiviral effect against influenza A virus by balancing the host's immune cells and the expression of inflammatory cytokines.
Our recent work demonstrated that Fufang Yinhua Jiedu granule (FFYH) exhibited a good antiviral activity against influenza A virus (IAV). However, whether the combinations of FFYH with antiviral agents show synergistic action against IAV remains unclear.
In vitro combinations of FFYH and oseltamivir against IAV were evaluated using Madin-Darby canine kidney (MDCK) cell model. In vivo combinations effect against IAV (H1N1, A/FM1/1/33) was performed using Institute of Cancer Research (ICR) mice model. The potential mechanism of FFYH against IAV in vitro and in vivo was investigated by RT-PCR or Western blot.
In vitro combinations of FFYH and oseltamivir could synergistically inhibit the replication of IAV and prevent the cell pathogenic effect (CPE) caused by IAV. In in vivo assays, FFYH combined with oseltamivir not only could markedly improve the sick signs, food intake, weight loss, hematology parameters, inflammatory factors and lung pathological changes, but also significantly increased the survival rate and the survival time of the IAV-infected mice. In addition, virus titers in lung tissue and lung index were markedly reduced on day 6 post-infection by combination therapy of oseltamivir combined with FFYH at 0.25 and 0.5 g/kg/d. The studies of mechanism of action indicated that the combination effect of FFYH with oseltamivir against IAV might be achieved through regulating TLR7-MyD88 signaling pathway.
The combinations of FFYH and oseltamivir not only exhibited in vitro synergistic antiviral activity on IAV, but also showed better protective effect against lethal IAV infections than oseltamivir or FFYH each on its own. These findings might provide a new option for the treatment of IAV infection in the future.
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