Mitochondria can be used as important biomarkers of pollutants on human health, and fine particulate matter (PM2.5) has been documented to cause respiratory damage. However, current studies about the ...relationship between PM2.5 and mitochondria in respiratory tract are limited and warrant further detailed investigations. Hence, the study was aimed to evaluate effects of PM2.5 on mitochondrial structure, investigate the link between PM2.5-induced mitochondrial disorder and respiratory damage, and delineate the possible mechanisms using both in vitro and in vivo models. PM2.5 exposure resulted in damage of mitochondrial structure, including mitochondrial dynamic, DNA biogenesis and morphological alteration 16HBE cells. Furthermore, PM2.5 elevated ROS formation. However, DPI and NAC (inhibitor of ROS) in supplement restored PM2.5-induced mitochondrial disorder. PM2.5 also contributed to the 16HBE cells apoptosis via mitochondrial pathway. Additionally, the results coincided with the in vivo data which were obtained from bronchial tissues of SD rats exposed to PM2.5 for 30 days. Collectively, this study uncovers that PM2.5 leads to the disorder of mitochondrial structure via ROS generation, and then results in respiratory damage. It provides further understanding about the detrimental effect of PM2.5 on respiratory damage, and reveals a mechanistic basis for preventing outcomes in polluted environments.
Exposure to fine particulate matter (PM2.5) has a close association with respiratory damage. Vitamin c and quercetin have been documented to possess antioxidant and anti-inflammation properties. ...However, their potential protective effects against PM2.5-induced respiratory damage have not been evaluated yet. Hence, the study was aimed to investigate their protective effects and delineate the possible mechanisms. The results indicated that PM2.5 depleted the cell viability of 16HBE cells, elevated reactive oxygen species (ROS) generation, and inhibited mitochondrial genes expressions, including fusion proteins Mfn1 and OPA1, along with biogenesis markers SIRT1 and p53R2. Additionally, the damage of mitochondrial morphology was observed upon PM2.5 exposure using both JC-1 and MitoTracker Red staining. Expressions of mitochondrial respiratory chain genes including NDUFS2 and UQCRI1 were also attenuated by PM2.5 exposure. Furthermore, PM2.5 promoted the mRNA levels of NADPH oxidase and inflammation cytokines. However, the addition of vitamin c or quercetin strikingly antagonized the PM2.5-induced toxic effects. Collectively, these findings suggest that vitamin c and quercetin have repressive roles in respiratory oxidative damage incurred by PM2.5, which provide the theoretical basis about intervention and control of food nutrients on PM2.5-induced human adverse health.
•Vitamin c and quercetin can relief the toxicity caused by PM2.5 on 16HBE cells.•Vitamin c and quercetin prominently alleviate the PM2.5-induced ROS generation.•Vitamin c and quercetin supplement significantly counteract the NOX2 and p67phox expressions incurred by PM2.5.•Vitamin c and quercetin have suppressive roles in mitochondrial structure and function damaged by PM2.5.•Vitamin c and quercetin play protective effects on inflammation response affected by PM2.5.
Tetrabromobisphenol A (TBBPA) and its derivatives are the common flame-retardants that may increase the risk of development of many types of cancers, including liver cancer. However, the effects of ...TBBPA in the development and progression of liver cancer remains unknown. This study investigated the potential effects of TBBPA on a metastatic phenotype of hepatocellular carcinoma cell line-HepG2. Our results revealed that TBBPA significantly promoted the migration and invasion via affecting the number and distribution of lysosomes in HepG2 cells in a dose-dependent manner. Moreover, TBBPA decreased the intracellular protein levels of Beta-Hexosaminidase (HEXB), Cathepsin B (CTSB) and Cathepsin D (CTSD) while increased the extracellular CTSB and CTSD. It entailed that TBBPA exposure could promote the lysosomal exocytosis in cancer cells. The reversal results were obtained after adding lysosomal exocytosis inhibitor vacuolin-1. Docking results suggested that TBBPA could bind to TRPML1. It was consistent with the binding position of agonist ML-SA1. TRPML1 knockdown significantly decreased the invasion and migration, and the results were reversed when TBBPA was added. The results were indicated that TRPML1 was critical in lysosomal exocytosis. In addition, our results showed that TBBPA-TRPML1 complex regulated the calcium-mediated lysosomal exocytosis, thereby promoting the metastasis in liver cancer cells. It was expected that our data could provide important basis for understanding the molecular mechanism(s) of TBBPA promoting invasion and migration of hepatoma cells and give rise to profound concerns of TBBPA exposure on human health.
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•The structure-activity relationship of TBBPA and derivatives was revealed.•A cell model was established based on lysosomes for the evaluation of TBBPA tumor effects.•TBBPA participated in lysosomal exocytosis is reported for the very first time.•The underlying mechanism(s) of TBBPA-mediated liver cancer progression was elucidated.
Tetrabromobisphenol A (TBBPA), one of the highly common industrial brominated flame retardants (BFRs), has been recently reported to influence the progression of endometrial carcinoma. However, the ...underlying mechanism between them has not been fully illuminated. Our findings demonstrated that treatment with low concentrations of TBBPA significantly induced the proliferation of Ishikawa cells in a concentration- and time-dependent manner. Mechanically, TBBPA stimulation led to the elevation of NF-κB expression, accompanied by the occurrence of ubiquitin-mediated IκB′ degradation. Additionally, the upregulation of pro-inflammatory cytokines upon TBBPA exposure was observed in both mRNA and protein levels. Interestingly, the above toxic effects of TBBPA on Ishikawa cells were markedly attenuated by the addition of MG-132, a proteasome inhibitor, suggesting the crucial role of ubiquitin-mediated IκB′ degradation in the TBBPA-stimulated proliferation of Ishikawa cells. Confirmation using in vivo model was also presented in this work. Accordingly, our data indicated that ubiquitin-mediated IκB′ degradation and inflammatory response could serve as critical and sensitive biomarkers for the TBBPA-induced endometrial carcinoma, which would be helpful for the future carcinogenic risk assessments of TBBPA exposure on uterus.
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•Low concentrations of TBBPA promoted the proliferation of Ishikawa cells.•TBBPA induced the elevation of NF-κB and reduction of IκB.•Ubiquitin-mediated IκB′ degradation was responsible for the increase of NF-κB upon TBBPA exposure.•TBBPA stimulated the inflammatory response in Ishikawa cells.
Atmospheric PM2.5 exposure greatly contributes to the incidence of and mortality from cardiovascular disease (CVD). Owing to the crucial role of vascular calcification in the progression of CVD, it ...is imperative to elucidate the effects of PM2.5 on vascular calcification to understand the toxic mechanisms of haze-induced CVD. However, the effects of PM2.5 exposure on vascular calcification and the underlying molecular mechanisms are still unclear. In this work, the in vitro and in vivo models were used to illuminate the effects of PM2.5 on vascular calcification. We found that PM2.5 promoted the deposition of hydroxyapatite in calcifying vascular cells. Moreover, hydroxyapatite deposition was significantly enhanced by 3.5 times compared with those in the control group in aortas of ApoE-/- mice after exposure winter PM2.5 (1.5 mg/kg b.w.), accompanied by activation of the OPG/RANKL pathway and inflammatory cytokines’ expressions. Moreover, PM2.5-induced reactive oxygen species (ROS) generation was observed. NAC, an ROS inhibitor, observably alleviated the promotion effects of PM2.5 on vascular calcification. Furthermore, rutin effectively prevented vascular calcification by regulating the OPG/RANKL pathway. Our results suggest that PM2.5 play an important role in the occurrence and development of vascular calcification, and that rutin has an antagonistic effect on it.
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•PM2.5 exposure promoted vascular calcification in vitro and in vivo.•PM2.5 promotes vascular calcification by activating the OPG/RANKL signaling pathway.•The rutin effectively reversed the promoting effects of PM2.5 on vascular calcification.
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•Real indoor VOC disturbed liver lipid metabolism, characterized by the decreased TG and DG.•Machine learning identified five serum biomarkers for liver lipid metabolism ...disorders.•Dual-omics analysis revealed the upregulated Dgkq as crucial regulator for TG reduction.•VOC downregulated FoxO, thus promoting Dgkq upregulation in lipid metabolism.
As a widespread indoor air pollutant, volatile organic compound (VOC) caused various adverse health effects, especial the damage to liver, which has become a growing public concern. However, the current toxic data are intrinsically restricted in the single or major VOC species. Limited knowledge is available regarding toxic effects, biomarkers and underlying mechanisms of real indoor VOC-caused liver damage. Herein, an indoor relevant VOC exposure model was established to evaluate the hepatic adverse outcomes. Machine learning and multi-omics approaches, including liver lipidomic, serum lipidomic and liver transcriptomic, were utilized to uncover the characteristics of liver damage, serum lipid biomarkers, and involved mechanism stimulated by VOC exposure. The result showed that indoor relevant VOC led to the abnormal hepatic lipid metabolism, mainly manifested as a decrease in triacylglycerol (TG) and its precursor substance diacylglycerol (DG), which could be contributed to the occurrence of hepatic adverse outcomes. In terms of serum lipid biomarkers, five lipid biomarkers in serum were uncovered using machine learning to reflect the hepatic lipid disorders induced by VOC. Multi-omics approaches revealed that the upregulated Dgkq disturbed the interconversion of DG and phosphatidic acid (PA), leading to a TG downregulation. The in-depth analysis revealed that VOC down-regulated FoxO transcription factor, contributing to the upregulation of Dgkq. Hence, this study can provide valuable insights into the understanding of liver damage caused by indoor relevant VOC exposure model VOC exposure, from the perspective of multi-omics analysis.
Lab biomineralization should be carried out in an actual clinical practice. This study evaluated self-etch adhesive as a carrier for amorphous calcium phosphate (ACP) nanoprecursors to continuously ...deliver biomimetic remineralization of self-assembly type I collagen and demineralized dentin. Si-containing ACP particles (Si-ACP) stabilized with polyaspartic acid (PAsp) were synthesized and characterized by transmission electron microscopy (TEM), scanning electron microscopy–energy-dispersive X-ray spectroscopy, Fourier transform infrared analysis, X-ray powder diffractometry, and X-ray phototelectron spectroscopy. The biomimetic remineralization of single-layer reconstituted type I collagen fibrils and demineralized dentin was analyzed by using two one-bottle self-etch dentin adhesives (Clearfil S3 Bond (S3), Kurraray-Noritake; Adper Easy One (AEO), 3 M ESPE) as a carrier loaded (or not, in the case of the control) with 25 wt % of Si-ACP particles. In vitro cytotoxicity assessed by the Cell Counting Kit-8 indicated that the Si-ACP particles had no adverse effect on cell viability. The capacity for Ca and P ions release from cured Si-ACP-containing adhesives (S3, AEO) was evaluated by inductively coupled plasma-atomic emission spectrometry, revealing the successively increasing release of Ca and P ions for 28 days. The intra- and extrafibrillar remineralization of type I collagen and demineralized dentin was confirmed by TEM and selected-area electron diffraction when the adhesives were used as a carrier loaded with Si-ACP particles. Therefore, we propose self-etch adhesive as a novel carrier for ACP nanoprecursors to continuously deliver biomimetic remineralization.
This study evaluated the influence of polydopamine treatment on the surface properties and bond strength of yttria‐stabilised tetragonal zirconia polycrystal (Y‐TZP). Sixty‐three zirconia blocks ...(10 × 10 × 2 mm) were randomly divided into three groups defined by surface treatment: (i) control group (C), (ii) grit‐blasted with 110 μm alumina particles (GB), and (iii) polydopamine (PDA) coating. The surfaces of specimens subjected to different treatments were investigated by X‐ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and water contact angle measurements. After the surface treatments, the specimens were cemented to resin composite cylinders. After bonding, the shear bond strength of the ceramic to the resin was measured, and the failure mode of each specimen was analysed using a stereomicroscope. The results indicated that the shear bond strength is highest for the GB treatment and lowest for the controls. However, the difference between groups GB and PDA was not statistically significant. In the control group, adhesive failure was predominant, whereas in the treatment groups, mixed mode failure was predominant. The pre‐treatment of Y‐TZP ceramic with the polydopamine coating might improve the bond strength of the resin cement to the zirconia ceramic.
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