Maternal PFOS exposure in mice induces hepatic lipid accumulation and inflammation in adult female offspring: Involvement of microbiome-gut-liver axis and autophagy.

Perfluorooctane sulfonates (PFOS) are the persistent organic pollutants. In the present study, 0, 0.3, or 3-mg/kg PFOS were administered to pregnant mice from GD 11 to GD 18. The histopathology of liver and intestine, serum and hepatic lipid levels, lipid metabolism related genes, and gut microbiota were examined in adult female offspring. The results suggested that maternal PFOS exposure increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and induced F4/80+ macrophage infiltration in adult female offspring, in addition to the elevation of TNF-α and IL-1ß mRNA levels in low-dose and high-dose groups, respectively. Furthermore, maternal exposure to PFOS increased serum triglyceride (TG) and hepatic total cholesterol (TC) levels, which was associated with the alteration of the process of fatty acid transport and ß-oxidation, TG synthesis and transport, cholesterol synthesis and excretion in the liver. The AMPK/mTOR/autophagy signaling was also inhibited in the liver of adult female offspring. Moreover, changes in gut microbiota were also related to lipid metabolism, especially for the Desulfovibrio, Ligilactobacillus, Enterorhabdus, HT002 and Peptococcaceae_unclassified. Additionally, maternal exposure to PFOS decreased mRNA expressions of the tight junction protein and AB+ goblet cells in the colon, while increasing the overproduction of lipopolysaccharides (LPS) and F4/80+ macrophage infiltration. Collectively, maternal PFOS exposure induced liver lipid accumulation and inflammation, which strongly correlated with the disruption of the gut-liver axis and autophagy in adult female offspring, highlighting the persistent adverse effects in offspring exposed to PFOS.

PM2.5 induce neurotoxicity via iron overload and redox imbalance mediated-ferroptosis in HT22 cells.

PM2.5 is an important risk factor for the development and progression of cognitive impairment-related diseases. Ferroptosis, a new form of cell death driven by iron overload and lipid peroxidation, is proposed to have significant implications. To verify the possible role of ferroptosis in PM2.5-induced neurotoxicity, we investigated the cytotoxicity, intracellular iron content, iron metabolism-related genes, oxidative stress indices and indicators involving in Nrf2 and ferroptosis signaling pathways. Neurotoxicity biomarkers as well as the ferroptotic cell morphological changes were determined by Western Blot and TEM analysis. Our results revealed that PM2.5 induced cytotoxicity, lipid peroxidation, as indicated by MDA content, and neurotoxicity via Aß deposition in a dose-related manner. Decreased cell viability and excessive iron accumulation in HT-22 cells can be partially blocked by ferroptosis inhibitors. Interestingly, GPX activity, Nrf2, and its regulated ferroptotic-related proteins (i.e. GPX4 and HO-1) were significantly up-regulated by PM2.5. Moreover, gene expression of DMT1, TfR1, IRP2 and FPN1 involved in iron homeostasis and NCOA4-dependent ferritinophagy were activated after PM2.5 exposure. The results demonstrated that PM2.5 triggered ferritinophagy-dependent ferroptotic cell death due to iron overload and redox imbalance. Activation of Nrf2 signaling pathways may confer a protective mechanism for PM2.5-induced oxidative stress and ferroptosis.

Silver nanoparticles induce iron accumulation-associated cognitive impairment via modulating neuronal ferroptosis.

Silver nanoparticles (AgNPs) are widely used in daily life and medical fields owing to their unique physicochemical properties. Daily exposure to AgNPs has become a great concern regarding their potential toxicity to human beings, especially to the central nervous system. Ferroptosis, a newly recognized programmed cell death, was recently reported to be associated with the neurodegenerative process. However, whether and how ferroptosis contributes to AgNPs-induced neurotoxicity remain unclear. In this study, we investigated the role of ferroptosis in neurotoxic effects induced by AgNPs using in vitro and in vivo models. Our results showed that AgNPs induced a notable dose-dependent cytotoxic effect on HT-22 cells and cognitive impairment in mice as indicated by a decline in learning and memory and brain tissue injuries. These findings were accompanied by iron overload caused by the disruption of the iron transport system and activation of NCOA4-mediated autophagic degradation of ferritin. The excessive free iron subsequently induced GSH depletion, loss of GPX and SOD activities, differential expression of Nrf2 signaling pathway elements, down-regulation of GPX4 protein and production of lipid peroxides, initiating ferroptosis cascades. The mitigating effects of ferrostatin-1 and deferoxamine on iron overload, redox imbalance, neuronal cell death, impairment of mice learning and memory, Aß deposition and synaptic plasticity reduction suggested ferroptosis as a potential molecular mechanism in AgNPs-induced neurotoxicity. Taken together, these results demonstrated that AgNPs induced neuronal cell death and cognitive impairment with Aß deposition and reduction of synaptic plasticity, which were mediated by ferroptosis caused by iron-mediated lipid peroxidation. Our study provides new insights into the underlying mechanisms of AgNPs-induced neurotoxicity and predicts potential preventive strategies.

Research progress in the degradation of printing and dyeing wastewater using chitosan based composite photocatalytic materials.

The surge in economic growth has spurred the expansion of the textile industry, resulting in a continuous rise in the discharge of printing and dyeing wastewater. In contrast, the photocatalytic method harnesses light energy to degrade pollutants, boasting low energy consumption and high efficiency. Nevertheless, traditional photocatalysts suffer from limited light responsiveness, inadequate adsorption capabilities, susceptibility to agglomeration, and hydrophilicity, thereby curtailing their practical utility. Consequently, integrating appropriate carriers with traditional photocatalysts becomes imperative. The combination of chitosan and semiconductor materials stands out by reducing band gap energy, augmenting reactive sites, mitigating carrier recombination, bolstering structural stability, and notably advancing the photocatalytic degradation of printing and dyeing wastewater. This study embarks on an exploration by initially elucidating the technical principles, merits, and demerits of prevailing printing and dyeing wastewater treatment methodologies, with a focal emphasis on the photocatalytic approach. It delineates the constraints encountered by traditional photocatalysts in practical scenarios. Subsequently, it comprehensively encapsulates the research advancements and elucidates the reaction mechanisms underlying chitosan based composite materials employed in treating printing and dyeing wastewater. Finally, this work casts a forward-looking perspective on the future research trajectory of chitosan based photocatalysts, particularly in the realm of industrial applications.

Repeated radon exposure induced epithelial-mesenchymal transition-like transformation via disruption of p53-dependent mitochondrial function.

Backgrouds: As a human carcinogen, radon and its progeny are the second most important risk factor for lung cancer after smoking. The tumor suppressor gene, p53, is reported to play an important role in the maintenance of mitochondrial function. In this work, we investigated the association between p53 and p53-responsive signaling pathways and radon-induced carcinogenesis. Methods: After repeated radon exposure, the malignant characteristics, cell cycle arrest, cell apoptotic rate, adenosine triphosphate (ATP) content, reactive oxygen species (ROS) level, mitochondrial DNA (mtDNA) copy number as well as indicative biomarkers involved in mitochondrial energy metabolism were evaluated in BEAS-2B cells or BALB-c mouse lung tissue. Results: Radon exposure induced epithelial-mesenchymal transition (EMT)-like transformation in BEAS-2B cells, as indicated by increased cell proliferation and migration. Additional mitochondrial alterations, including decreased ATP content, increased ROS levels, mtDNA copy numbers, cell apoptosis, and G2/M cell cycle arrest were observed. Radon exposure caused an energy generation shift from aerobic respiration to glycolysis as reflected by increased expression of TIGAR and p53R2 proteins and decreased expression of SCO2 protein in BEAS-2B cells, and increased expression of p53, SCO2 and TIGAR proteins in mouse lung tissue, respectively. The effects of p53 deficiency on the prevention of mitochondrial dysfunction suggested a protective role of p53 in radon-induced malignant-like features in BEAS-2B cells. Conclusions: Repeated radon exposure induced EMT-like transformation in BEAS-2B cells via disruption of mitochondrial function. Activation of p53 and p53-responsive signaling pathways in BEAS-2B cells and BALB-c mice may confer a protective mechanism for radon-induced lung injury.

Comprehensive removal of various dyes by thiourea modified chitosan/nano ZnS composite via enhanced photocatalysis: Performance and mechanism.

Dyeing wastewater is a carcinogenic pollutant, which is widely known for its harmful effects on humans and marine organisms. In this study, a novel composite was prepared by blending thiourea modified chitosan with zinc sulfide nanoparticles (T-CS/ZnS) to comprehensively remove methyl orange (MO), rhodamine B (Rh B), and methylene blue (MB) effectively. Characterization results suggested that the synthesized composite has an irregular and rough surface that provided high specific surface area for adsorption process, while the strong optical response and low bandgap width contributed to the subsequent photocatalytic degradation of adsorbed dye molecules. Under optimum experimental conditions, the removal rates of MO, Rh B, and MB were 99.59 %, 99.49 %, and 91.04 %, respectively. Amino and hydroxyl groups provide electrons in photocatalytic reactions. The reaction process is consistent with the quasi-first-order kinetic model, and the material has good stability and regeneration potential. This study indicated that T-CS/ZnS composite is a highly effective material for the treatment of dyeing wastewaters.

Synthesis of triethylenetetramine modified sodium alginate/CuS nanocrystal composite for enhanced Cr(VI) removal: Performance and mechanism.

Photocatalysis has been widely used for the removal of hexavalent chromium from wastewater as an efficient and environmental friendly method. However, conventional photocatalysts generally exhibit poor adsorption properties toward Cr(VI), resulting in unsatisfactory performance in high concentrated wastewaters. In this study, we synthesized a novel composite material with high Cr(VI) adsorption ability by blending prepared CuS nanocrystals into triethylenetetramine modified sodium alginate for the enhanced photocatalytic removal of Cr(VI). Effect of CuS dosage, pH value, light source and intensity were discussed for the optimum Cr(VI) removal conditions. The synthesized composite has shown good adsorption performance toward Cr(VI) and the overall removal rate reached 98.99 % within 50 min under UV light irradiation with citric acid as hole scavenger. Adsorption isotherm, thermodynamics, and kinetics with corresponding model fitting were discussed, which suggested that the monolayer and chemical adsorption dominated the adsorption process. Characterization results indicated that amino and hydroxyl groups contributed electrons in the photocatalysis reaction for the reduction of Cr(VI) to Cr(III). CuS nanocrystals can enhance the surface charge and light absorbance ability of the composite, and the Cr(VI) removal was governed by electrostatic interaction and photo-induced redox reaction.

Silver Nanoparticles Induce a Size-dependent Neurotoxicity to SH-SY5Y Neuroblastoma Cells via Ferritinophagy-mediated Oxidative Stress.

Silver nanoparticles (AgNPs) are widely used in a variety of consumer products because of their antibacterial and antifungal characteristics, but little is known about their toxicity to the brain. In this study, we investigated AgNP-induced neurotoxicity using the human neuroblastoma cancer (SH-SY5Y) cell line. After a 24 h treatment of AgNPs with two primary sizes (5 and 50 nm labeled as Ag-5 and Ag-50, respectively), a series of toxicological endpoints including cell viability, expression of proteins and genes in amyloid precursor protein (APP) amyloid hydrolysis process and ferritinophagy signaling pathways, oxidative stress, intracellular iron levels, and molecular regulators of iron metabolism were evaluated. Our results showed that both Ag-5 and Ag-50 induced notable neurotoxic effects on SH-SY5Y cells indicated by cell proliferation inhibition, increased BACE1 protein expression, and decreased APP and ADAM10 gene expression. Activation of nuclear receptor coactivator 4-mediated ferritinophagy and blockade of autophagic flux were induced by AgNPs, accompanied by intracellular iron accumulation and overexpression of divalent metal-ion transporter-1 and ferroportin1 in SH-SY5Y cells. In addition, AgNPs significantly decreased glutathione peroxidase 4 protein expression but increased malondialdehyde concentration, suggesting that AgNP-induced iron accumulation may trigger oxidative stress by disruption of the intracellular oxidant and antioxidant systems. In addition, compared with Ag-50, Ag-5 with higher cellular uptake efficiency caused more detrimental effects on SH-SY5Y cells. In conclusion, our findings demonstrated a size-dependent neurotoxicity in SH-SY5Y cells by AgNPs via ferritinophagy-mediated oxidative stress.

PM2.5 induces inflammatory responses via oxidative stress-mediated mitophagy in human bronchial epithelial cells.

BACKGROUND: Fine particulate matter (PM2.5) is a ubiquitous air pollutant, and it has been reported to be closely associated with lung inflammatory injury. In this study, the potential molecular mechanisms underlying PM2.5-induced cellular inflammation in human bronchial epithelial (BEAS-2B) cells were investigated. MATERIALS AND METHODS: Ambient PM2.5 particulates from Suzhou, China, were collected and re-suspended in ultrapure water. Cellular damages, characterized by oxidative stress, mitochondrial injury, and inflammatory cytokine production, were determined in 24 h PM2.5-treated BEAS-2B cells with or without 3-methyladenine (3-MA; autophagy inhibitor) pretreatment. Biomarkers related to oxidative damage, inflammatory injury and autophagy signaling pathways were also measured. RESULTS: Uptake of PM2.5 in BEAS-2B cells induced cellular oxidative damage, mitochondrial injury, and inflammatory responses as indicated by a significant decrease in GSH/GSSG ratio, increased MDA content, dilated mitochondria with loss and rupture of crista, and production of inflammatory cytokines. Activation of Nrf-2/TXNIP-mediated NF-κB and Bnip3L/NIX-dependent mitophagy signaling pathways, as well as accumulation of autophagosomes and autolysosomes, were also observed. A 6 h pretreatment of 3-MA increased PM2.5-induced oxidative damage and cellular inflammation as indicated by increasing protein levels of HO-1, TXNIP, Bnip3L/NIX and IL-8 gene expression. CONCLUSIONS: PM2.5 induced cellular inflammatory injury by oxidative stress, mitochondrial dysfunction, and mitophagy initiation. Although induction of Bnip3L/NIX-mediated mitophagy in BEAS-2B cells appeared to confer protection in response to PM2.5, dysfunction of autophagic flux may be a critical contributor to defective mitophagy and cellular inflammatory response.

Repeated radon exposure induced lung damage via oxidative stress-mediated mitophagy in human bronchial epithelial cells and mice.

This study aimed to investigate the potential molecular mechanism underlying radon-induced lung damage. Our results showed that long-term radon exposure induced mitochondrial damage and redox imbalance in BEAS-2B cells and a time-dependent lung pathological injury in mice. The activation of Nrf-2 and its down-stream antioxidants, and the gene expression of the indicated markers at different stages of autophagy were found to be induced with the increasing of radon exposure time. Changes in the gene expression of PINK-1, Parkin, and p62 induced by radon showed differences in mechanisms of mitophagy activation and profiles of autophagic flux between BEAS-2B cells and mice. Our findings not only demonstrated that long-term radon exposure induced damages to bronchial epithelial cells and the mice lung through increasing oxidative stress, decreasing mitochondrial function and activating mitophagy with different profiles of autophagic flux, but also revealed Nrf-2 as a central regulator of mitochondrial homeostasis and lung damage.

Sex-Specific Neurotoxicity of Dietary Advanced Glycation End Products in APP/PS1 Mice and Protective Roles of Trehalose by Inhibiting Tau Phosphorylation via GSK-3ß-TFEB.

SCOPE: It remains unclear whether dietary advanced glycation end products (dAGEs)-induced cognitive impairment is sex-dependent. Trehalose may antagonize dAGEs-induced neurotoxicity via glycogen synthase kinase-3 beta (GSK3ß)-transcription factor EB (TFEB) signaling. METHODS AND RESULTS: The sex-specific neurotoxicity of dAGEs and the protective role of trehalose are investigated both in vivo and in vitro. Both sexes of APP/PS1 mice are divided into three groups: that is, control, dAGEs, and dAGEs supplemented with trehalose. SHSY-5Y cells incubated with AGE-BSA and trehalose are also utilized. Dietary AGEs impair cognitive function only in female mice, which is restored by trehalose. Trehalose upregulates phosphorylated-GSK3ß serine9 (p-GSK3ß ser9), TFEB and transient receptor potential mucolipin 1, ADAM10, oligosaccharyl transferase-48, estrogen receptor α and induces TFEB nuclear translocation in hippocampus, elevates IDE and ERß in cortex, while reduces p-tau ser396&404, CDK5, cathepsin B, and glial fibrillary acidic protein in hippocampus. Trehalose elevates p-GSK3ß ser9, induces TFEB nuclear translocation, consequently reverses AGE-BSA-induced tau phosphorylation in vitro. CONCLUSIONS: Female mice are more susceptible to the deleterious effects of dAGEs on cognitive function, which may be owing to its regulation on ERß. Trehalose can strongly reverse dAGEs-induced tau phosphorylation by potentiating TFEB nuclear translocation via inhibiting GSK-3ß.

Association between visceral adipose index and risk of hypertension in a middle-aged and elderly Chinese population.

BACKGROUND AND AIMS: Visceral adipose index (VAI) had been widely used to predict the risks of several diseases. However, few studies have clarified the association between VAI and the risk of hypertension in Chinese population. Thus, we investigate the association between VAI and the increased risk of hypertension in a nationwide cohort of middle-aged and elderly adults in China. METHODS AND RESULTS: Data were obtained from the China Health and Retirement Longitudinal Study from 2011 to 2015. A total of 5200 Chinese participants aged 45 years and older were included. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of hypertension, with the lowest quartile of VAI score group as the reference. During the 4-years follow-up, 979 cases of hypertension were recorded. Compared with those in the lowest VAI score group, the participants with the highest quartile of VAI score were at a higher risk level of hypertension (HR: 1.454; 95% CI 1.204 to 1.755), especially subjects living in the urban area (2.142, 1.522 to 3.014). Furthermore, VAI can improve the ability of both BMI and WC in predicting the risk of hypertension by 12.72% (95% CI: 5.78%-19.67%) and 10.12% (95% CI: 3.17%-17.07%), respectively. CONCLUSION: In summary, VAI was positively associated with an increased risk of hypertension among a middle-aged and elderly Chinese population; VAI score can improve the ability of BMI and WC in predicting risk of hypertension.

Silver nanoparticles: Correlating particle size and ionic Ag release with cytotoxicity, genotoxicity, and inflammatory responses in human cell lines.

The widespread use of silver nanoparticles (AgNPs), their many sources for human exposure, and the ability of AgNPs to enter organisms and induce general toxicological responses have raised concerns regarding their public health and environmental safety. To elucidate the differential toxic effects of polyvinylpyrrolidone-capped AgNPs with different primary particle sizes (i.e. 5, 50, and 75 nm), we performed a battery of cytotoxicity and genotoxicity assays and examined the inflammatory responses in two human cell lines (i.e. HepG2 and A549). Concentration-dependent decreases in cell proliferation and mitochondrial membrane potential and increases in cytokine (i.e. interleukin-6 and interleukin-8) excretion indicated disruption of mitochondrial function and inflammation as the main mediating factors of AgNPs-induced cytotoxicity. An incremental increase in genotoxicity with decreasing AgNPs diameter was noted in HepG2 cells, which was associated with S and G2/M accumulation and transcriptional activation of the GADD45α promoter as reflected by luciferase activity. Dose-related genetic damage, as indicated by Olive tail moment and micronucleus formation, was also observed in A549 cells, but these effects as well as the AgNPs-induced cytotoxicity were more associated with ionic Ag release from nanoparticles (NPs). In summary, the present study addressed different toxicity mechanisms of AgNPs, depending on the cell model, toxicological endpoint, particle size, and degree of Ag+ release from NPs. The results suggest that the GADD45α promoter-driven luciferase reporter cell system provided a rapid screening tool for the identification of genotoxic properties of NPs across a range of different sizes and concentrations.

Cellular effects of PM2.5 from Suzhou, China: relationship to chemical composition and endotoxin content.

Exposure to PM2.5 can cause adverse health outcomes. In this study, we analyzed PM2.5 samples collected from suburban and urban sites, including a traffic tunnel in Suzhou, China, for their physicochemical properties, endotoxin contents, and effects on HepG2 and A549 cells in vitro. The greatest cellular responses, including oxidative stress, cytotoxicity, genotoxicity, inflammatory, and transcriptional activation of stress-responsive genes (i.e., HSPA1A, GADD45α), were observed in cells treated with traffic tunnel PM2.5. Cytokine expression was also measured and closely correlated with endotoxin content, while other toxic effects were largely related to PM2.5-bound metals and polycyclic aromatic hydrocarbons (PAHs). These findings suggested that chemical and biological composition of PM2.5, including adsorbed trace metals, PAHs, and endotoxin, may contribute significantly to their toxicity. In addition to commonly used in vitro toxicity tests, HSPA1A and GADD45α promoter-driven luciferase reporter cells may provide a potential new tool for rapid screening and quantification of PM2.5 toxicity.

[Algorithm for Estimating Tissue Strain Based on Optical Flow].

Because the translation hypothesis of optical flow method can not accurately describe the form of motion after tissue compression, so we proposed a new ultrasonic elastic imaging algorithm. It was assumed that the deformation of the tissue was affine transformation when the probe was pressed to the tissue, and the displacement and strain distribution were estimated simultaneously by the optical flow method combined with the prior estimation. In order to verify the effectiveness of the algorithm, the imaging quality of the algorithm and the other imaging algorithm were compared with the simulated radio frequency echo signal. The results show that the new algorithm is higher in signal to noise ratio (SNRe), contrast to noise ratio (CNRe) and running speed than the contrast algorithm under 8% compression. The results show that the new proposed algorithm can effectively estimate axial displacement and axial strain in the case of large compression.

1,25-Dihydroxy Vitamin D3 Attenuates the Oxidative Stress-Mediated Inflammation Induced by PM2.5via the p38/NF-κB/NLRP3 Pathway.

Vitamin D3 is reported to be involved in the regulation of inflammatory processes. In this study, biomarkers related to oxidative stress and inflammation were investigated to clarify the protective effects and possible mechanism of 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) on PM2.5-induced inflammatory response. In the in vitro study using human bronchial epithelial (HBE) cells, aqueous extracts of PM2.5 could induce oxidative damage which is characterized by significant increases in production of reactive oxygen species, malonaldehyde concentration, and protein expression of HSPA1A and HO-1. Meanwhile, PM2.5 caused secretion of inflammatory factors (IL-6, IL-8) in the culture medium as well as phosphorylation of p38, nuclear factor-kappa B (NF-κB) inhibitor alpha (IκBα), and NF-κB p65 proteins. Increases in NLRP3 expression was also observed in HBE cells after PM2.5 exposure. However, all these biomarkers were remarkably attenuated by a 24-h pretreatment of 1 nM 1,25-(OH)2D3. Furthermore, 1,25-(OH)2D3 also reduced transcriptional activation of NF-κB induced by PM2.5 as indicated by a significant decrease in luciferase activity in HBE cells stably transfected with the NF-κB response element (RE)-driven luciferase reporter. Taken together, our findings provided novel experimental evidences supporting that vitamin D3 could reduce the predominantly oxidative stress-mediated inflammation induced by PM2.5via the p38/NF-κB/NLRP3 signaling pathway.

The association between transforming growth factor beta1 polymorphism and susceptibility to pulmonary fibrosis: A meta-analysis (MOOSE compliant).

Although many studies have investigated the association of single nucleotide polymorphisms (SNPs) in transforming growth factor beta1 (TGF-ß1) gene with pulmonary fibrosis (PF), but their association is still controversial. To clarify this, we performed a meta-analysis.Studies related to TGF-ß1 and PF were retrieved from PubMed, Medline, Embase, Scopus, and Wanfang (up to November 30, 2017). We targeted TGF-ß1 SNPs that have been reported by ≥3 studies to be included in the current meta-analysis, resulting in only 1 final SNP (rs1800470). The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in the models of allele comparison (T vs C), homozygote comparison (TT vs CC), dominant (TT vs TC + CC), recessive (TT + TC vs CC) to evaluate the strength of the associations.A total of 7 case-control studies were included in this meta-analysis. Overall, no significant association between TGF-ß1 rs1800470 and PF was found (T vs C: OR [95% CI] = 0.96 [0.80, 1.15]; TT vs CC: 0.87 [0.61, 1.22]; TT vs TC + CC: 0.80 [0.62, 1.04]; TT + TC vs CC: 1.13 [0.83, 1.54]). In subgroup analyses by ethnicity or original disease, no statistically significant association between TGF-ß1 rs1800470 polymorphisms and PF was demonstrated.This meta-analysis revealed that TGF-ß1 rs1800470 polymorphism was not associated with susceptibility to PF development.

Cytotoxicity and genotoxicity of nanosilver in stable GADD45α promoter-driven luciferase reporter HepG2 and A549 cells.

OBJECTIVES: The intense commercial application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse health effects to human. This study aimed to explore the potency of AgNPs to induce GADD45α gene, an important stress sensor, and its relationships with the cytotoxicity and genotoxicity elicited by AgNPs. METHODS: Two established HepG2 and A549 cell lines containing the GADD45α promoter-driven luciferase reporter were treated with increasing concentrations of AgNPs for 48 hours. After the treatment, transcriptional activation of GADD45α indicated by luciferase activity, cell viability, cell cycle arrest, and levels of genotoxicity were determined. The uptake and intracellular localization of AgNPs, cellular Ag doses as well as Ag+ release were also detected. RESULTS: AgNPs could activate GADD45α gene at the transcriptional level as demonstrated by the dose-dependent increases in luciferase activity in both the reporter cells. The relative luciferase activity was greater than 12× the control level in HepG2-luciferase cells at the highest concentration tested where the cell viability decreased to 17.0% of the control. These results was generally in accordance with the positive responses in cytotoxicity, cell cycle arrest of Sub G1 and G2/M phase, Olive tail moment, micronuclei frequency, and the cellular Ag content. CONCLUSIONS: The cytotoxicity and genotoxicity of AgNPs seems to occur mainly via particles uptake and the subsequent liberation of ions inside the cells. And furthermore, the GADD45α promoter-driven luciferase reporter cells, especially the HepG2-luciferase cells, could provide a new and valuable tool for predicting nanomaterials genotoxicity in humans.

Depot-specific effects of treadmill running and rutin on white adipose tissue function in diet-induced obese mice

White adipose tissue (WAT) is a critical organ involved in regulating metabolic homeostasis under obese condition. Strategies that could positively affect WAT function would hold promise for fighting against obesity and its complications. The aim of the present study is to explore the effects of treadmill exercise training and rutin intervention on adipose tissue function from diet-induced obese (DIO) mice and whether fat depot-specific effects existed. In epididymal adipose tissue, high-fat diet (HFD) resulted in reduction in adiponectin mRNA expression, peroxisome proliferator-activated receptors (PPAR)-γ and DsbA-L protein expression, elevation in endoplasmic reticulum (ER) stress markers including 78 kDa glucose-regulated protein (GRP-78), C/EBP homologous protein (CHOP) and p-c-Jun N-terminal kinase (JNK). Isoproterenol-stimulated lipolysis and insulin stimulated Akt phosphorylation ex vivo were blunted from HFD group. The combination of rutin with exercise (HRE) completely restored GRP78 and p-JNK protein expression to normal levels, as well as blunted signaling ex vivo. In inguinal adipose tissue, HFD led to increased adiponectin mRNA expression, PPAR-γ, GRP78, and p-JNK protein expression, and reduction in DsbA-L. HRE is effective for restoring p-JNK, PPAR-γ, and DsbA-L. In conclusion, depot-specific effects may exist in regard to the effects of rutin and exercise on key molecules involved in regulating adipose tissue function (i.e., ER stress markers, PPAR-γ and DsbA-L, adiponectin expression, and secretion, ex vivo catecholamine stimulated lipolysis and insulin stimulated Akt phosphorylation) from DIO mice (AU)

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