Circadian disturbances by altering the light-dark cycle negatively affects hematopoietic function of bone marrow in mice.

Circadian rhythms in metabolically active tissues are crucial for maintaining physical health. Circadian disturbance (CD) can cause various health issues, such as metabolic abnormalities and immune and cognitive dysfunctions. However, studies on the role of CD in immune cell development and differentiation, as well as the rhythmic expression of the core clock genes and their altered expression under CD, remain unclear. Therefore, we exposed C57bl/6j mice to repeated reversed light-dark cycles for 90 days to research the effects of CD on bone marrow (BM) hematopoietic function. We also researched the effects of CD on endogenous circadian rhythms, temporally dependent expression in peripheral blood and myeloid leukocytes, environmental homeostasis within BM, and circadian oscillations of hematopoietic-extrinsic cues. Our results confirmed that when the light and dark cycles around mice were frequently reversed, the circadian rhythmic expression of the two main circadian rhythm markers, the hypothalamic clock gene, and serum melatonin, was disturbed, indicating that the body was in a state of endogenous CD. Furthermore, CD altered the temporally dependent expression of peripheral blood and BM leukocytes and destroyed environmental homeostasis within the BM as well as circadian oscillations of hematopoietic-extrinsic cues, which may negatively affect BM hematopoiesis in mice. Collectively, these results demonstrate that circadian rhythms are vital for maintaining health and suggest that the association between CD and hematopoietic dysfunction warrants further investigation.

Early-life exposure to PM2.5 leads to ASD-like phenotype in male offspring rats through activation of PI3K-AKT signaling pathway.

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms.

Oil mistparticulate matter exposure induces hyperlipidemia-related inflammation via microbiota/ SCFAs/GPR43 axis inhibition and TLR4/NF-κB activation.

Metabolites produced by the human gut microbiota play an important role in fighting and intervening in inflammatory diseases. It remains unknown whether immune homeostasis is influenced by increasing concentrations of air pollutants such as oil mist particulate matters (OMPM). Herein, we report that OMPM exposure induces a hyperlipidemia-related phenotype through microbiota dysregulation-mediated downregulation of the anti-inflammatory short-chain fatty acid (SCFA)-GPR43 axis and activation of the inflammatory pathway. A rat model showed that exposure to OMPM promoted visceral and serum lipid accumulation and inflammatory cytokine upregulation. Furthermore, our research indicated a reduction in both the "healthy" microbiome and the production of SCFAs in the intestinal contents following exposure to OMPM. The SCFA receptor GPR43 was downregulated in both the ileum and white adipose tissues (WATs). The OMPM treatment mechanism was as follows: the gut barrier was compromised, leading to increased levels of lipopolysaccharide (LPS). This increase activated the Toll-like receptor 4 Nuclear Factor-κB (TLR4-NF-κB) signaling pathway in WATs, consequently fueling hyperlipidemia-related inflammation through a positive-feedback circuit. Our findings thus imply that OMPM pollution leads to hyperlipemia-related inflammation through impairing the microbiota-SCFAs-GPR43 pathway and activating the LSP-induced TLR4-NF-κB cascade; our findings also suggest that OMPM pollution is a potential threat to humanmicrobiota dysregulation and the occurrence of inflammatory diseases.

Identification of potential glioma drug resistance target proteins based on ultra-performance liquid chromatography-mass spectrometry differential proteomics.

In this study, to screen for candidate markers of temozolomide (TMZ) resistance in glioblastoma, we artificially established TMZ drug-resistant glioblastoma (GBM) cell lines, U251-TMZ and U87-TMZ. In the U251-TMZ and U87-TMZ cell lines, we screened and analyzed differentially expressed proteins using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) differential proteomics. Compared with the U251 and U87 control cell lines, 95 differential proteins were screened in the U251-TMZ and U87-TMZ cell lines, of which 28 proteins were upregulated and 67 proteins were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the co-upregulated proteins showed that most of the differentially expressed proteins were located in the cytoplasm and were significantly upregulated in the biological processes related to vesicular transport in the intimal system and inflammatory response mediated by myeloid leukocytes. Seven candidates were identified as potential GBM markers of TMZ resistance. Combined with existing research findings, our study supports that UAP1L1 and BCKDK are promising potential markers of TMZ resistance in GBM. This is important for further understanding the molecular mechanisms that drive the development and enhancement of TMZ resistance.

Correction: Jia et al. Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice. Toxics 2023, 11, 127.

In the original publication [...].

Short-term PM2.5 exposure induces transient lung injury and repair.

Exposure to fine atmospheric particulate matter (PM) is known to induce lung inflammation and injury; however, the way in which sophisticated endogenous lung repair and regenerative programs respond to this exposure remains unknown. In this study, we established a whole-body mouse exposure model to mimic real scenarios. Exposure to fine PM (PM with an aerodynamic diameter ≤ 2.5 µm [PM2.5]; mean 1.05 mg/m3) for 1-month elicited inflammatory infiltration and epithelial alterations in the lung, which were resolved 6 months after cessation of exposure. Immune cells that responded to PM2.5 exposure mainly included macrophages and neutrophils. During PM2.5 exposure, alveolar epithelial type 2 cells initiated rapid repair of alveolar epithelial mucosa through proliferation. However, the reparative capacity of airway progenitor cells (club cells) was impaired, which may have been related to the oxidative production of neutrophils or macrophages, as suggested in organoid co-cultures. These data suggested that the pulmonary toxic effects of short-term exposure to fine atmospheric PM at a certain dosage could be overcome through tissue reparative mechanisms.

Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice.

Extensive environmental pollution by microplastics has increased the risk of human exposure to plastics. However, the biosafety of polypropylene microplastics (PP-MPs), especially of PP particles < 10 µm, in mammals has not been studied. Thus, here, we explored the mechanism of action and effect of exposure to small and large PP-MPs, via oral ingestion, on the mouse intestinal tract. Male C57BL/6 mice were administered PP suspensions (8 and 70 µm; 0.1, 1.0, and 10 mg/mL) for 28 days. PP-MP treatment resulted in inflammatory pathological damage, ultrastructural changes in intestinal epithelial cells, imbalance of the redox system, and inflammatory reactions in the colon. Additionally, we observed damage to the tight junctions of the colon and decreased intestinal mucus secretion and ion transporter expression. Further, the apoptotic rate of colonic cells significantly increased after PP-MP treatment. The expression of pro-inflammatory and pro-apoptosis proteins significantly increased in colon tissue, while the expression of anti-inflammatory and anti-apoptosis proteins significantly decreased. In summary, this study demonstrates that PP-MPs induce colonic apoptosis and intestinal barrier damage through oxidative stress and activation of the TLR4/NF-κB inflammatory signal pathway in mice, which provides new insights into the toxicity of MPs in mammals.

Effects of Different Concentrations of Oil Mist Particulate Matter on Pulmonary Fibrosis In Vivo and In Vitro.

Oil-mist particulate matter (OMPM) refers to oily particles with a small aerodynamic equivalent diameter in ambient air. Since the pathogenesis of pulmonary fibrosis (PF) has not been fully elucidated, this study aims to explore the potential molecular mechanisms of the adverse effects of exposure to OMPM at different concentrations in vivo and in vitro on PF. In this study, rats and cell lines were treated with different concentrations of OMPM in vivo and in vitro. Sirius Red staining analysis shows that OMPM exposure could cause pulmonary lesions and fibrosis symptoms. The expression of TGF-ß1, α-SMA, and collagen I was increased in the lung tissue of rats. The activities of MMP2 and TIMP1 were unbalanced, and increased N-Cadherin and decreased E-Cadherin upon OMPM exposure in a dose-dependent manner. In addition, OMPM exposure could activate the TGF-ß1/Smad3 and TGF-ß1/MAPK p38 signaling pathways, and the differentiation of human lung fibroblast HFL-1 cells. Therefore, OMPM exposure could induce PF by targeting the lung epithelium and fibroblasts, and activating the TGF-ß1/Smad3 and TGF-ß1/MAPK p38 signaling pathways.

Different exposure modes of PM2.5 induces bronchial asthma and fibrosis in male rats through macrophage activation and immune imbalance induced by TIPE2 methylation.

Exposure to PM2.5 can aggravate the occurrence and development of bronchial asthma and fibrosis. Here, we investigated the differences in bronchial injury caused by different exposure modes of PM2.5 (high concentration intermittent exposure and low concentration continuous exposure), and the mechanism of macrophage activation and respiratory immune imbalance induced by PM2.5, leading to bronchial asthma and airway fibrosis using animal and cell models. A "PM2.5 real-time online concentrated animal whole-body exposure system" was used to conduct PM2.5 respiratory exposure of Wistar rats for 12 weeks, which can enhance oxidative stress in rat bronchus, activate epithelial cells and macrophages, release chemokines, recruit inflammatory cells, release inflammatory factors and extracellular matrix, promote bronchial mucus hypersecretion, inhibit the expression of epithelial cytoskeletal proteins, destroy airway barrier, and induce asthma. Furthermore, PM2.5 induced M2 polarization in lung bronchial macrophages through JAK/STAT and PI3K/Akt signaling pathways, and compared with low concentration continuous exposure, high concentration intermittent exposure of PM2.5 could regulate significantly higher expression of TIPE2 protein through promoter methylation of TIPE2 DNA, thereby activating PI3K/Akt signaling pathway and more effectively inducing M2 polarization of macrophages. Additionally, activated macrophages release IL-23, and activated epithelial cells and macrophages released TGF-ß1, which promoted the differentiation of Th17 cells, triggered the Th17 dominant immune response, and activated the TGF-ß1/Smad2 signaling pathway, finally causing bronchial fibrosis. Moreover, when the total amount of PM2.5 exposure was equal, high concentration-intermittent exposure was more serious than low concentration-continuous exposure. In vitro experiments, the co-culture models of PM2.5 with BEAS-2B, WL-38 and rat primary alveolar macrophages further confirmed that PM2.5 could induce the macrophage activation through oxidative stress and TIPE2 DNA methylation, and activate the TGF-ß1/Smad2 signaling pathway, leading to the occurrence of bronchial fibrosis.

Acute exercise in ozone-polluted air induces apoptosis in rat quadriceps femoris muscle cells via mitochondrial pathway.

Ozone (O3) pollution can decrease sport performance and induce respiratory toxicity, but relatively few studies have investigated its effects on skeletal muscles. We randomly assigned rats to the following groups based on a 2 â€‹× â€‹4 two-factor factorial design: Air+0, Air+10, Air+15, and Air+20, O3+0, O3+10, O3+15, and O3+20. The rats in the +0 groups rested, whereas those in the +10, +15, and +20 groups ran on a treadmill (in clean air for Air groups and in air polluted with 0.14 â€‹parts per million [ppm] O3 for O3 groups) at speeds of 10, 15, and 20 â€‹m/min, respectively, for 1 â€‹h. Thereafter, key enzyme activities involving the tricarboxylic acid cycle, oxidative phosphorylation, adenosine triphosphate (ATP) content, histopathological changes, oxidative stress, inflammation factors, and apoptosis were assessed in the rat quadriceps femoris samples. Ozone reduced key enzyme activities and ATP contents in the quadriceps femoris regardless of whether the rats exercised. Pathological changes, inflammatory factors, oxidative stress, and mitochondria-dependent apoptosis were only evident under conditions of exercise combined with ozone and increasingly worsened as exercise intensity increased. These findings suggested that acute exercise under ozone exposure could induce damage to the quadriceps femoris, which would negatively affect sport performance. Ozone-induced disrupted energy metabolism might be an early event that becomes more critical as exercise intensity increases. Therefore, care should be taken when exercising in polluted air, even when ozone pollution is mild.

Combined multi-omics analysis reveals oil mist particulate matter-induced lung injury in rats: Pathological damage, proteomics, metabolic disturbances, and lung dysbiosis.

Oil mist particulate matter (OMPM) causes acute and chronic diseases and exacerbations. Owing to the characteristics of poor ventilation, high oil mist concentration, and a relatively closed working environment, the existence of OMPM in the cabin is inevitable, and its impact on the health of occupations on ships cannot be ignored. However, compared with several studies that summarized the health effects of OMPM from traditional sources, few studies have focused on the occupational exposure risk of OMPM from oil pollution sources in ships. In this study, we collected OMPM from oil pollution in cabins and assessed the exposure to OMPM from oil pollution and the corresponding health risks through acute exposure experiments in rats. OMPM exposure induces protein regulation in the extracellular matrix and immune responses, leading to severe inflammatory responses. The abundance and composition of the lung microbial community changed significantly. It interferes with the lung metabolite levels. However, more research is needed to fully understand the extent of health risks associated with OMPM exposure. Further research on vulnerable groups exposed to OMPM from ships is needed to inform public health interventions.

[Effects of early life PM2.5 exposure on prefrontal cortex of offspring male rats].

Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P＜0.01), the level of MT were decreased significantly (P＜0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P＜0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P＜0.01), and the level of ROS was increased significantly (P＜0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P＜0.01, P＜0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P＜0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.

[Effect of epithelial-mesenchymal transition on cardiac fibrosis induced by oil mist particulate matter].

Objective: To investigate the effects of oil-mist particulate matter (OMPM) on cardiac tissue structure fibrosis in rats and the role of epithelial-mesenchymal transition (EMT). Methods: Six-week-old Wistar rats (half male and half female) were randomly divided into 3 groups: control group (without OMPM exposure), low-dose exposure group (50 mg/m3) and high-dose exposure group (100 mg/m3), 18 rats in each group, with 6.5 hours per day of dynamic inhalation exposure. After 42 days of continuous exposure, cardiac tissues were collected for morphological observation; Western blot was used to detect fibrosis markers collagen I and collagen III levels, epithelial marker E-cadherin levels, interstitial markers N-cadherin, fibronectin, vimentin, alpha-smooth muscle actin (α-SMA) levels, and EMT transcription factor Twist protein levels; Real-time polymerase chain reaction (RT-qPCR) was used to detect collagen I and collagen III mRNA levels. Results: After OMPM exposure, myocardial cell edema and collagen fiber deposition were increased gradually with increasing exposure dose. Western blot results showed that compared with the control group, the expression levels of collagen I, collagen III, N-Cadherin, fibronectin, vimentin, α-SMA, and Twist protein were increased significantly in the low-dose exposure group and the high-dose exposure group (P＜0.01), and protein expression levels were higher in the high-dose exposure group than those in the low-dose exposure group (P＜0.01). In contrast, E-Cadherin protein expression levels were decreased significantly, and lower in the high-dose exposure group (P＜0.01). RT-qPCR results showed that compared with the control group, collagen I and collagen III mRNA levels were increased significantly in the low-dose exposure group and the high-dose exposure group (P＜0.01), and were increased with increasing exposure dose. (P＜0.01). Conclusion: OMPM may induce cardiac fibrosis in rats by promoting EMT process.

The damage effect of heat stress and psychological stress combined exposure on uterus in female rats.

AIMS: Explore the effects of heat stress and psychological stress combined exposure on the uterus and its underlying mechanisms. MAIN METHODS: Sixty female Sprague-Dawley rats were randomly assigned to four groups: control group, psychological stress group, high ambient temperature group, and high ambient temperature combined with psychological stress group. All treatments were administered for two weeks. During this period, the estrous cycle, body weights and rectal temperature were measured regularly. Then, ovarian weight coefficient, serum estradiol (E2) and progesterone (P) concentration, uterine histomorphological alterations, levels of tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD), and the expressions of ovarian hormone receptors, leukemia inhibitory factor (LIF) and its receptor, homeobox gene A10 (HoxA10), Wnt5a, Wnt7a, ß-catenin, and P-ß-cateninY142 in the uterus and endometrium were detected. KEY FINDINGS: High temperature combined with psychological stress lead to body weight, body temperature, ovarian hormones and estrus cycle disorder, uterine gland ducts expansion and endometrial thickness reduction, and the decreased expression of endometrial receptivity markers (LIF and HoxA10). Further, disturbed expression of E2 and P receptors in endometrium, elevated MDA and TNF-α levels, and decreased Wnt5a, Wnt7a and P-ß-cateninY142 content were found. Our data suggested that co-exposure to high temperature and psychological stress could aggravate uterine damage probably by inducing ovarian hormonal disorder and the subsequent oxidative stress and inflammation, and reduce the endometrial function through suppressing Wnt signaling. SIGNIFICANCE: This will provide the scientific basis for improving female reproductive health, and preventing and treating reproductive disorders.

Effects of noise and low-concentration carbon monoxide exposure on rat immunity.

OBJECTIVE: To evaluate the immunotoxicity and effects of noise and/or low-concentration carbon monoxide (CO) exposure on immune organs and immune functions in rats. METHODS: Male Wistar rats exposed to 98 dB(A) white noise and/or 100 ppm CO 4 h/d for 30 d were used to determine the pathological changes in the thymus and spleen, and variations in leukocyte counts, inflammatory factors, and immunoglobulin (Ig) concentrations. RESULTS: The boundaries of the cortex and medulla of the thymus were unclear following noise and combined exposure. The pathological changes in spleen after CO and combined exposure included blurred boundaries of red-pulp and white-pulp, disappearance of normal splenic nodules and neutrophil infiltration. After exposure to noise and in combination, leukocyte and lymphocyte counts decreased significantly. After exposure to low-concentration CO and in combination, serum IgM and IgG levels decreased significantly, but the levels of tumor necrosis factor-α and interferon-γ levels increased significantly. Eosinophils and IgA levels decreased significantly following exposure to noise and/or low concentration of CO, while the level of interleukin-1 increased significantly. Monocytes increased significantly only under noise or CO exposure, but not under combined exposure. CONCLUSIONS: Noise and/or low-concentration CO exposure may suppress innate and adaptive immune functions and induce inflammatory responses. Noise exposure mainly affected the innate immune function of rats, whereas low-concentration CO exposure mainly affected adaptive immune functions. Combined exposure presented higher immunotoxicity than noise or CO alone, suggesting that exposure to noise and low-concentration CO in the living and working environments can affect the immune system.

Exposure to copper oxide nanoparticles triggers oxidative stress and endoplasmic reticulum (ER)-stress induced toxicology and apoptosis in male rat liver and BRL-3A cell.

Copper oxide nanoparticles (Nano-CuO) toxicity has been researched widely in recent years. However, the relationship between oxidative stress and ER-stress and the possible mechanisms induced by Nano-CuO have been rarely studied. Here, the mechanism of hepatotoxicity and apoptosis through oxidative stress and ER-stress induced by Nano-CuO was investigated in vivo and in vitro. In in vivo experiments, male Wistar rats were intranasally instilled 10 µg Nano-CuO/g body weight daily for 60 days, which caused liver function impairment, oxidative stress, inflammatory response, histopathological and ultrastructural damage, ER-stress and apoptosis in liver tissue. in vitro experiments on rat hepatocytes BRL-3A cells showed that exposure to Nano-CuO for 24 h resulted in excess production of reactive oxygen species leading to decrease in mitochondria membrane potential causing cell death by inducing apoptosis. However, administration of n-acetyl cysteine decreased the apoptosis in Nano-cuo treated group. The in vivo and in vitro experiments confirmed that oxidative stress triggered ER-stress pathway, leading to the opening of apoptosis pathways of CHOP, JNK, and Caspase-12. In summary, treatment of Nano Cuo triggered oxidative stress by ROS, which in turn resulted in activation of ER stress pathways causing cell death in liver tissue and BRL-3A cells.

Toxic effects of the food additives titanium dioxide and silica on the murine intestinal tract: Mechanisms related to intestinal barrier dysfunction involved by gut microbiota.

This study aimed to compare the effects of three food-grade particles (micro-TiO2, nano-TiO2, and nano-SiO2) on the murine intestinal tract and to investigate their potential mechanisms of action. A 28-day oral exposure murine model was established. Samples of blood, intestinal tissues and colon contents were collected for detection. The results showed that all three particles could cause inflammatory damage to the intestine, with nano-TiO2 showing the strongest effects. Exposure also led to changes in gut microbiota, especially mucus-associated bacteria. Our results suggest that the toxic effects on the intestine were due to reduced intestinal mucus barrier function and an increase in metabolite lipopolysaccharides which activated the expression of inflammatory factors downstream. In mice exposed to nano-TiO2, the intestinal PKC/TLR4/NF-κB signalling pathway was activated. These findings will raise awareness of toxicities associated with the use of food-grade TiO2 and SiO2.

Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice.

PM2.5 and formaldehyde (FA) are major outdoor and indoor air pollutants in China, respectively, and both are known to be harmful to human health and to be carcinogenic. Of all the known chronic health effects, leukaemia is one of the most serious health risks associated with these two pollutants. To explore the influence and underlying mechanisms of exposure to formaldehyde and PM2.5 on hematopoietic toxicity, we systematically studied the toxicity induced in hematopoietic organs: bone marrow (BM); spleen; and myeloid progenitor cells (MPCs). Male Balb/c mice were exposed to: PM2.5 (20, 160 µg/kg·d) at a dose of 40 µL per mouse or formaldehyde (0.5, 3.0 mg/m3) for 8 h per day for 2 weeks or co-exposed to formaldehyde and PM2.5 (20 µg/kg·d PM2.5 + 0.5 mg/m3 FA, 20 µg/kg·d PM2.5 + 3 mg/m3 FA, 160 µg/kg·d PM2.5 + 0.5 mg/m3 FA, 160 µg/kg·d PM2.5 + 3 mg/m3 FA) for 2 weeks. Similar toxic effects were found in the formaldehyde-only and PM2.5-only groups, including significant decrease of blood cells and MPCs, along with decreased expression of hematopoietic growth factors. In addition, individual exposure of formaldehyde or PM2.5 increased oxidative stress, DNA damage and immune system disorder by destroying the balance of Th1/Th2, and Treg/Th17. DNA repair was markedly inhibited by deregulating the mammalian target of rapamycin (mTOR) pathway. Combined exposure to PM2.5 and formaldehyde led to more severe effects. Administration of Vitamin E (VE) was shown to attenuate these effects. In conclusion, our findings suggested that PM2.5 and formaldehyde may induce hematopoietic toxicity by reducing the expression of hematopoietic growth factors, increasing oxidative stress and DNA damage, activating the 'immune imbalance' pathway and suppressing the DNA-repair related mTOR pathway. The hematopoietic toxicity induced by combined exposure of PM2.5 and formaldehyde might provide further insights into the increased incidence of hematological diseases, including human myeloid leukaemia.

Neurotoxicity of aluminum oxide nanoparticles and their mechanistic role in dopaminergic neuron injury involving p53-related pathways.

The central nervous system is a potential target for Al2O3 nanoparticles (Nano-Al2O3). Here, we investigated the effects of intranasal instillation of Nano-Al2O3 on the distribution and damage in crucial functional sub-brain regions of rats. In vivo results show that Nano-Al2O3 was translocated into the brain via the olfactory nerve pathway. Nano-Al2O3 accumulated in the hippocampus, olfactory bulb, cerebral cortex, and striatum, causing ultrastructural changes, oxidative damage, inflammatory responses, and histopathological damage in sub-brain regions. As indicated by in vitro studies, cell viability decreased with the addition of Nano-Al2O3, which increased the levels of lactate dehydrogenase and oxidative stress. Nano-Al2O3 also impaired mitochondrial function, disturbed the cell cycle and induced apoptosis. In addition, Nano-Al2O3 decreased the expression of cyclin D1, bcl-2, Mdm2, and phospho-Rb and increased the expression of p53, p21, Bax, and Rb. Therefore, oxidative stress, mitochondrial dysfunction, and p53-related pathways might be important in the process of dopaminergic neurotoxicity induced by Nano-Al2O3. The current study establishes a striatum damage model and identifies molecular biomarkers of dopaminergic neuron damage induced by Nano-Al2O3. In brief, our study demonstrates that Nano-Al2O3 exposure can be a risk factor for neurodegenerative diseases and may negatively impact the hippocampus, striatum, and dopaminergic neurons.

Identification of apoptosis-associated protein factors distinctly expressed in cigarette smoke condensate-exposed airway bronchial epithelial cells.

Smoking is associated with an increased risk of respiratory diseases, including lung cancer and asthma. However, the mechanisms or diagnostic markers for smoking-related diseases remain largely unknown. Here we investigated the role of cigarette smoke condensate (CSC) in the regulation of human bronchial epithelial cell (BEAS-2B) behavior. We found that exposure to CSC significantly inhibited BEAS-2B cell viability, impaired cell morphology, induced cell apoptosis, triggered oxidative damage, and promoted inflammatory response, which suggests a deleterious effect of CSC on bronchial epithelial cells. In addition, CSC markedly altered the expression of apoptosis-associated protein factors, including p21, soluble tumor necrosis factor receptor 1, and Fas ligand. In sum, our study identified a panel of novel protein factors that may mediate the actions of CSC on bronchial epithelial cells and have a predictive value for the development and progression of smoking-related diseases, thus providing insights into the development of potential diagnostic and therapeutic strategies against these diseases.