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1.
Artigo em Inglês | MEDLINE | ID: mdl-32436098

RESUMO

With the accelerated pace of economic development and modernization, air pollution has become one of the most focused public health problems. However, the impact of particulate matter exposure during pregnancy on childhood asthma and wheezing remains controversial. We performed this meta-analysis to explore the relationship between prenatal exposure to PM2.5 and childhood asthma and wheezing. Candidate papers were searched on PubMed, Web of Science, Embase, and Cochrane Library before July 15, 2019. The main characteristics of the included studies were extracted, and the quality was evaluated by the Newcastle-Ottawa Scale (NOS). A sensitivity analysis was performed to assess the impact of individual studies on the combined effects. The Egger and Begg tests were conducted to examine the publication bias. Nine studies were included in the final analysis. Prenatal exposure to PM2.5 significantly increased the risk of childhood asthma and wheezing (OR = 1.06, 95% CI 1.02-1.11; per 5 µg/m3). Maternal exposure was more strongly related to childhood asthma and wheezing before age 3 (OR = 1.15, 95% CI 1.00-1.31; per 5 µg/m3) than after (OR = 1.04, 95% CI 1.00-1.09; per 5 µg/m3). Children in developed countries showed more severe effects (OR = 1.14, 95% CI 1.02-1.27; per 5 µg/m3). Children who were born to mothers with higher levels of prenatal exposure were at higher risk of asthma and wheezing (OR = 1.07, 95% CI 1.02-1.13; per 5 µg/m3). This meta-analysis indicated that the impact of PM2.5 on childhood asthma and wheezing begins as early as utero, so regulating pollutant emission standards and strengthening prenatal protection are crucial to maternal and child health.

2.
J Hazard Mater ; 397: 122608, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32387827

RESUMO

Epidemiological studies revealed a sharp increase in respiratory diseases attributed to PM2.5. However, the underlying mechanisms remain unclear. Evidence suggested mitochondrion as a sensitive target upon the stimulus of PM2.5, and the centrality in the pathological processes and clinical characterization of lung diseases. To investigate cell fate and related mechanisms caused by PM2.5, we exposed human lung epithelial cells (BEAS-2B) to PM2.5 (0-100 µg/mL). Consequently, PM2.5 components were found in cytoplasm, and morphological and functional alterations in mitochondria occurred, as evidenced by loss of cristae, vacuolization and even the outer mitochondrial membrane rupture, mitochondrial membrane potential collapse, enhanced reactive oxygen species (ROS)/mtROS level, calcium overload, suppressed cellular respiration and ATP production in PM2.5-treated cells. Further, disturbed dynamics toward fission was clearly observed in PM2.5-treated mitochondria, associated with DRP1 mitochondrial translocation and phosphorylation. Besides, PM2.5 induced mitochondria-mediated apoptosis. More importantly, mechanistic results revealed ROS- and DRP1-mediated mitochondrial fission in a reciprocal way, and DRP1 inhibitor (Mdivi-1) significantly alleviated the pro-apoptotic effect of PM2.5 through reversing the activated mitochondrial apoptotic pathway. In summary, our results firstly revealed PM2.5 induced apoptosis in lung epithelial cells through a ROS-DRP1-mitochodrial fission axis-mediated mitochondrial apoptotic pathway, ultimately contributing to the onset and development of pulmonary diseases.

3.
Sci Total Environ ; 730: 138982, 2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32388108

RESUMO

BACKGROUND: Air pollution is a serious environmental problem in China. This study was designed to investigate whether exposure to particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) before pregnancy is associated with gestational diabetes mellitus (GDM) and fasting glucose in China. METHODS: We recruited subjects and collected clinical data from the Nanjing Maternity and Child Health Care Hospital from July 2016 to October 2017. A series of validated land-use regression (LUR) models were built to assess individual exposure to PM2.5 in a 1 × 1 km area at both work and home addresses following a time-weighted pattern. Multiple linear regression and logistic regression analyses were performed to examine the association between PM2.5 exposure and GDM and fasting glucose. RESULTS: In total, 11,639 of 16,995 women were included in the final analysis. Among the 11,639 women, 2776 (23.85%) had GDM. Individual exposure to PM2.5 within three months before pregnancy ranged from 21.58 to 85.92 µg/m3. Positive associations were observed among the interquartile ranges (IQRs) of exposure to PM2.5 within three months before pregnancy and GDM (OR = 2.61, 95% CI: 1.40-4.93, p < .01) as well as fasting glucose levels (ß = 0.57, 95% CI: 0.45-0.68, p < .01). The diabetogenic effects of PM2.5 gradually increased from the first month before pregnancy, peaked in the second month and then gradually decreased until the third month when the week-specific exposure were analyzed to identify the sensitive time window. CONCLUSION: Our study confirmed that higher exposure to PM2.5 within three months before pregnancy is significantly associated with increased risk of GDM and elevated fasting glucose levels, reflecting the importance of preconceptional environmental exposure in the development of maternal GDM.

4.
Sci Total Environ ; 733: 139135, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32438194

RESUMO

Nowadays, the great majority of toxicological studies have focused on immediate cardiovascular effects of simultaneous exposure to long-term or short-term PM2.5; yet, whether the persistent vascular fibrosis will be induced after short-term PM2.5 exposure and its related underlying mechanisms remain unclear. In this study, we adopted SD rats treated with PM2.5 for 1 month and followed by 12 months and 18 months recovery. Results from Doppler ultrasonography and histopathological analysis found that PM2.5-evoked vascular fibrosis was comprised of structural injury, including thickening of aortic media and carotid intima media thickness (CIMT), narrow left common carotid artery (LCCA), collagen deposition, impaired elasticity and functional alterations in aortal stiffness during long-term recovery. The protein expression levels of collagen I, collagen III, proliferating cell nuclear antigen (PNCA), TGF-ß and osteopontin (OPN) remained elevated trends in PM2.5-treated groups for the related period than in control groups. Additionally, PM2.5 upregulated the protein expression levels of superoxide dismutase 2 (SOD2), mitochondrial fission related proteins (Drp1 and Fis1), while downregulated the protein expression levels of mitochondrial fusion related proteins (Mfn2 and OPA1). Moreover, PM2.5 significantly activated the mitophagy-related protein expression, including LC3, p62, PINK, Parkin. In summary, our results demonstrated that short-term PM2.5 exposure could trigger mitophagy, further lead to mitochondrial dysfunction which regulated persistent vascular fibrosis during long-term recovery.

5.
Environ Res ; 185: 109471, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32276169

RESUMO

BACKGROUND: Pregnancy complications, such as gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP), have a great impact on public health. Exposure to ambient air pollution during pregnancy may cause pregnancy complications. The aim of our study is to explore the risk of trimester-specific maternal exposure to air pollutants on complications of pregnancy. METHODS: PubMed, EMBASE, Web of Science, and Cochrane were systematically searched for cohort studies published before October 27, 2019 which reported the association between ambient air pollutants (PM2.5, PM10, CO, NO, NO2, NOx, O3, and SO2) and pregnancy complications (GDM, HDP, preeclampsia, and gestational hypertension) during different exposure windows. A meta-analysis was applied to combine relative risks (RRs) and their confidence intervals (CIs) from eligible studies. Quality assessment was conducted and Egger test was used to evaluate the publication bias. All statistical analyses were performed by STATA software (Version 15, StataCorp, College Station, Texas, USA). RESULTS: This meta-analysis consisted of 33 cohort studies conducted on 22,253,277 pregnant women. Meta-analyses showed during the first trimester, there were significant associations of PM10 with gestational hypertension (RR = 1.07, 95% CI: 1.02-1.12 per 10 µg/m3, I2 = 0.0%), of SO2 with GDM (RR = 1.04, 95% CI: 1.00-1.08 per 1 ppb increment, I2 = 54.1%), of PM2.5 with preeclampsia (RR = 0.97, 95% CI: 0.95-1.00 per 5 µg/m3, I2 = 4.1%). During the entire pregnancy, PM2.5 significantly increased the risk of hypertensive disorders of pregnancy (RR = 1.18, 95% CI: 1.02-1.34 per 5 µg/m3, I2 = 85.1%). Egger test indicated that wide-scale publication bias was unlikely. CONCLUSION: Maternal exposure to ambient air pollutants is associated with pregnancy complications especially during the first trimester. Further large multicenter cohort studies considering different constituents of pollutants, levels of disease severity, sensitive populations, and various exposure windows are warranted in the future research.

6.
Sci Total Environ ; 727: 138790, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32344260

RESUMO

Although the associations between endosulfan and adverse cardiovascular health have been reported, the toxic effects and underlying mechanism of endosulfan on the heart are not well understood. In this study, we examined the cardiotoxicity induced by endosulfan using Wistar rats and human cardiomyocytes (AC16) cells. Wistar rats were divided into control group (received corn oil alone) and three concentrations of endosulfan groups (1, 5 and 10 mg/kg·bw) by gavage. The AC16 cells were treated with three various concentrations (0, 1.25, 5, and 20 µg/mL) of endosulfan. The results showed that endosulfan induced cytotoxicity through damaging myocardial structure, decreasing the viability of cardiomyocytes, and elevating the serum levels of cardiac troponin I, heart fatty acid binding protein, aspartate aminotransferase, and reactive oxygen species (p < 0.05). Moreover, measurement of mitochondrial function showed that endosulfan could significantly decrease adenosine triphosphate levels and cytochrome c oxidase IV expression in AC16 cells (p < 0.05). In addition, endosulfan obviously inhibited Bcl-2 expression, activated the expressions of cytochrome c/Caspase-9/Caspase-3 signaling pathway, and induced the apoptosis of AC16 cells (p < 0.05). Furthermore, endosulfan significantly increased the expression of Bim, and inhibited the expressions of PI3K/Akt/FoxO3a signaling pathways in cardiomyocytes (p < 0.05). These results suggest that endosulfan may induce cardiotoxicity by inducing myocardial apoptosis resulting from activation of mitochondria-mediated apoptosis pathway and inhibition of pro-survival signaling pathways, which might be helpful in elucidating the mechanism of cardiac dysfunction induced by endosulfan.

7.
Int J Oncol ; 56(6): 1335-1351, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32236571

RESUMO

Bone morphogenetic proteins (BMP) are pluripotent molecules, co­ordinating cellular functions from early embryonic and postnatal development to tissue repair, regeneration and homeostasis. They are also involved in tumourigenesis, disease progression and the metastasis of various solid tumours. Emerging evidence has indicated that BMPs are able to promote disease progression and metastasis by orchestrating communication between cancer cells and the surrounding microenvironment. The interactions occur between BMPs and epidermal growth factor receptor, hepatocyte growth factor, fibroblast growth factor, vascular endothelial growth factor and extracellular matrix components. Overall, these interactions co­ordinate the cellular functions of tumour cells and other types of cell in the tumour to promote the growth of the primary tumour, local invasion, angiogenesis and metastasis, and the establishment and survival of cancer cells in the metastatic niche. Therefore, the present study aimed to provide an informative summary of the involvement of BMPs in the tumour microenvironment.

8.
Chemosphere ; 251: 126423, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32171134

RESUMO

Accumulating evidences support that exposure to fine particulate matter (PM2.5) could cause inflammation of the airway, but its underlying mechanisms are less known. Our study aimed to explore the potential effect of non-canonical NF-κB signaling pathway in airway inflammation, which caused by PM2.5, and the possible regulatory relationship between miR-6747-5p and NF-κB2. The histological analysis from in vivo study manifested that PM2.5 could induce the exudation and infiltration of polymorphonuclear leukocytes (PMNs). Immunohistochemistry results of lung tissues showed that PM2.5 increased ICAM-1, 6Ckine, SDF-1 and BAFF positive staining with a dose-dependent manner. In addition, PM2.5 could induce the p52 nuclear translocation to trigger non-canonical NF-κB signaling pathway in lung tissues and BEAS-2B cells. Targetscan reporter gene assay showed that there was a target regulatory relationship between miR-6747-5p and NF-κB2. Besides, the chemical mimics of miR-6747-5p weakened the activation of non-canonical NF-κB signaling pathway induced by PM2.5. In summary, exposure to PM2.5 could trigger airway inflammation by activating the non-canonical NF-κB signaling pathway, which may be related to the negative feedback regulation mechanism of miR-6747-5p. Our findings will give new ideas into the toxic effects of airway inflammation triggered by PM2.5.

9.
J Hazard Mater ; 391: 122203, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171159

RESUMO

Cardiac fibrosis is associated with fine particulate matter (PM2.5) exposure. In addition, whether high-fat diet (HFD) could exacerbate the PM2.5-induced cardiac injury was unevaluated. Thus, this study was aimed to investigate the combined effects of PM2.5 and HFD on cardiac fibrosis. The echocardiography and histopathological analysis showed that co-exposure of PM2.5 and HFD had a significant deleterious effect on both cardiac systolic and diastolic function accompanied the myofibril disorder and myocardial fibrosis in C57BL/6 J mice than exposed to PM2.5 or HFD alone. The augmented oxidative damage and increased α-SMA area percentage were detected in heart tissue of mice exposed to PM2.5 and HFD together. PM2.5 upregulated the expressions of cardiac fibrosis-related special markers, including collagen-I, collagen-III, TGF-ß1, p-Smad3 and total Smad3, which had more pronounced activations in co-exposure group. Meanwhile, the factorial analysis exhibited the synergistic interaction regarded to the combined exposure of PM2.5 and HFD. Simultaneously, PM2.5 and palmitic acid increased intracellular ROS generation and activated the TGF-ß1/Smad3 signaling pathway in cardiomyocytes. While the ROS scavenger NAC had effectively attenuated the ROS level and suppressed the TGF-ß1/Smad3 signaling pathway. Taken together, our results demonstrated combined exposure to PM2.5 and HFD could aggravate cardiac fibrosis via activating the ROS/TGF-ß1/Smad3 signaling pathway.

10.
Int J Biol Sci ; 16(3): 447-459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32015681

RESUMO

The mortality rate of lung cancer remains the highest amongst all cancers despite of new therapeutic developments. While cancer stem cells (CSCs) may play a pivotal role in cancer, mechanisms underlying CSCs self-renewal and their relevance to cancer progression have not been clearly elucidated due to the lack of reliable and stable CSC cellular models. In the present study, we unveiled the novel oncogene function of cadherin 1 (Cdh1) via bioinformatic analysis in a broad spectrum of human cancers including lung adenocarcinoma (LUAD), adding a new dimension to the widely reported tumor suppressor function of Cdh1. Experimentally, we show for the first time that Cdh1 promotes the self-renewal of lung CSCs, consistent with its function in embryonic and normal stem cells. Using the LLC-Symmetric Division (LLC-SD) model, we have revealed an intricate cross-talk between the oncogenic pathway and stem cell pathway in which Cdh1 functions as an oncogene by promoting lung CSC renewal via the activation of the Phosphoinositide 3-kinase (PI3K) and inhibition of Mitogen-activated protein kinase (MAPK) pathways, respectively. In summary, this study has provided evidence demonstrating effective utilization of the normal stem cell renewal mechanisms by CSCs to promote oncogenesis and progression.

12.
J Hazard Mater ; 391: 122206, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32036317

RESUMO

Increasing environmental exposure to silica nanoparticles (SiNPs) and limited cardiotoxicity studies posed a challenge for the safety evaluation and management of these materials. This study aimed to explore the adverse effects and underlying mechanisms of subacute exposure to SiNPs on cardiac function in rats. Results from echocardiographic, ultrastructural and histopathological analysis found that SiNPs induced cardiac contractile dysfunction, accompanied by incomplete myocardial structures, disordered sarcomere segments, interstitial edema and myocyte apoptosis in heart. Levels of myocardial enzymes and inflammatory factors were markedly increased in both serum and heart tissue, accompanied by elevated levels of oxidative damage occurred in the hearts of SiNPs-treated rats. SiNPs significantly upregulated the expressions of inflammation and contraction-related proteins, including JNK, p-JNK, c-Jun, TF and PAR1. Lentivirus transfection of JNK shRNA showed the low-expression of JNK-facilitated F-actin and inhibited TF in the SiNPs-treated cardiomyocytes. Moreover, SiNPs activated the mRNA and protein levels of JNK/TF/PAR1 pathway, and these effects were significantly dampened after JNK knock down. Our results demonstrate that SiNPs trigger myocardial contractile dysfunction via JNK/TF/PAR1 signaling pathway.

13.
Sci Total Environ ; 711: 134493, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32000304

RESUMO

Silica nanoparticles (SiNPs) have been widely used in human health related products, such as food additives, cosmetics and even drug delivery, gene therapy or bioimaging. Recently, a first-in-human clinical trial based on polyethylene glycol (PEG)-modified SiNPs had been approved by US FDA to trace melanoma. However, as a nano-based drug delivery system, its biocompatibility and vascular toxicity are still largely unknown. Thus, we synthesized the fluorescent SiNPs to explore the biocompatibility and vascular endothelial function, and compare different biological effects caused by PEG-modified and unmodified SiNPs in cells and zebrafish model. The characterizations of SiNPs and PEG-modified SiNPs were analyzed by TEM, SEM, AFM and DLS, which exhibited relatively good stable and dispersive. Compared with SiNPs, PEG-modified SiNPs had markedly reduced the inflammatory response and vascular damage in Tg (fli-1: EGFP) and Tg (mpo: GFP) transgenic zebrafish lines, respectively. Consistent with the in vivo results, the PEG-modified SiNPs had been found to significantly decline the levels of ROS, inflammatory cytokines and mitochondrial-mediated apoptosis in vascular endothelial cells compared to SiNPs, and the ROS scavenger NAC could effectively alleviate the above adverse effects induced by nanoparticles. Our results suggested that the PEG-modified SiNPs could become more safety via increasing the biocompatibility and decreasing cellular toxicities in living organisms.


Assuntos
Nanopartículas , Dióxido de Silício , Animais , Animais Geneticamente Modificados , Humanos , Polietilenoglicóis , Peixe-Zebra
14.
J Chem Phys ; 152(5): 054903, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32035450

RESUMO

By using a graphics processing unit-accelerated parallel algorithm on a compute unified device architecture platform, we perform large-scale molecular dynamics simulations in a Lennard-Jones system to observe the entire crystallization process, including metastable stage, critical nuclei formation, and the stage of crystal growth. Although the intermediated precursors that play a role in determining the polymorphs are predominantly bcc ordered, the polymorph selection is rather different at different stages. The precursors that have a relatively high orientational order will be on average in a denser region than uniform liquids, but microscopically the crystal nucleation happens without a density change. The average density of nuclei first increases significantly, and then almost keeps independent on the crystallite size after the growing post-critical nucleus becomes large enough. With such a large enough system, the crystal growth rate is able to be calculated directly by doing a linear fit to the temporal evolution of growing crystallite size. The obtained value of the growth rate indicates that the actual crystal growth in the Lennard-Jones system where the crystal-liquid interface has several kinds of structures is possibly driven by both collision-controlled and diffusion-controlled mechanisms.

15.
Oncol Rep ; 43(2): 562-570, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894335

RESUMO

Psoriasin, otherwise known as S100A7, is a member of the S100 protein family. With the key function of binding calcium, it is able to regulate a range of cellular functions. Altered Psoriasin expression is associated with poor clinical outcomes in several solid cancers. The present study aimed to examine the implication of Psoriasin in bladder cancer (BC). Expression of Psoriasin was examined in BC cell lines using PCR. Immunohistochemical (IHC) staining of Psoriasin was performed on a bladder disease spectrum tissue array. Plasmids were constructed to effectively knockdown and overexpress Psoriasin in BC cells and further utilized for in vitro BC cellular function assays. Association between Psoriasin expression and survival of patients with BC was evaluated using Kaplan­Meier survival analysis. Psoriasin was revealed to be expressed by both bladder epithelia and cancer cells as determined by IHC. Increased expression of Psoriasin was significantly correlated with a poor overall BC patient survival. Overexpression of Psoriasin in the EJ138 cell line increased cellular proliferation, adhesion and invasion, whereas knockdown exhibited the opposite effect on cellular functions in RT112 cells. Matrix metalloprotease (MMP)9 appeared to be the most affected of the three MMPs examined in these two BC cell lines. The analysis revealed a positive correlation in BC tumours between Psoriasin and MMP9. Overall, high Psoriasin expression was correlated with poor overall survival in BC patients and promoted invasiveness of BC cells via upregulation of MMPs. Psoriasin possesses certain prognostic and therapeutic potential in BC which requires further exploration.

16.
Sci Adv ; 6(1): eaax5576, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31911942

RESUMO

Cetuximab improves the survival of patients with metastatic colorectal cancer. The main limitation is primary and secondary resistance, the underlying mechanism of which requires extensive investigation. We proved that PRSS expression levels are significantly negatively associated with the sensitivity of cancer cells to cetuximab. Detailed mechanistic analysis indicated that PRSS can cleave cetuximab, leading to resistance. Cetuximab or bevacizumab combined with SPINK1, a PRSS inhibitor, inhibited cell growth more efficiently than cetuximab or bevacizumab alone in xenograft models. PRSS levels in the serum of 156 patients with mCRC were analyzed, and poor efficacy of cetuximab therapy was observed in patients with aberrant PRSS expression. PRSS expression in monoclonal antibody (mAb)-treated patients with cancer from The Cancer Genome Atlas database was also evaluated to determine whether patients with higher PRSS expression have significantly reduced progression-free survival. Our work provides a strong scientific rationale for targeting PRSS in combination with cetuximab therapy.

17.
Environ Int ; 136: 105444, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31935561

RESUMO

Epidemiological studies have confirmed that PM2.5 could contribute to the development of atherosclerosis accompanied with lipids dysregulation. However, the lipids biomarkers involved in this progress remain largely unknown. In this study, a targeted lipidomic approach was used to find out the possible lipid biomarkers involved in the development of atherosclerosis after PM2.5 exposure or during a recovery period. Also, we assessed the pro-atherosclerosis effects of PM2.5 and follow-up influence using pulse wave (PW) Doppler ultrasound, oil red O staining and H&E staining. The vascular stiffness was elevated after 2-month PM2.5 exposure and might persist after 1-month recovery. While the lesions mostly concentrated in the aortic arch was significantly increased in 2-month PM2.5 exposure group and remained an increasing trend after 1-month recovery. The expressions of pro-inflammatory cytokines detected by Mouse Inflammation Array were elevated after ApoE-/- mice treated with PM2.5 for 2-month and restored following 1-month recovery. Yet, IL-10 was significantly decreased during 1-month recovery. Additionally, the targeted lipidomic analysis demonstrated that cholesterol ester (CE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM) were significantly increased while lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC), diacylglycerol (DG), triacylglycerol (TG) were reduced after 2-month PM2.5 exposure, indicating that PM2.5 could disrupt glycerophospholipids, glycerolipids and sphingolipids metabolism. And a persistent impact of PM2.5 on glycerophospholipids and glycerolipids metabolism was found after 1-month recovery. Our study demonstrated that PM2.5-induced inflammation response might promote atherosclerotic lesions probably through lipid dysregulation, and the influence probably persisted after 1-month recovery.

18.
Talanta ; 209: 120517, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892092

RESUMO

Sulfide plays an important role in many important life processes, and abnormal levels of sulfide that may cause diseases. Sulfide is also essential in industrial production and food processing, and it is well concerned for environmental issues and food safety. In order to study the physiological and pathological effects of sulfide and the impact on the environment, it is still urgent to develop a convenient and effective sulfide detection technology. Here, we developed a ratiometric fluorescent probe 7-Nitro-1,2,3-benzoxoxadiazole-Acridoneacetylpiperazine (NBD-AAP) which is based on the fluorescence resonance energy transfer (FRET) between acridone and NBD fluorophores. The NBD-AAP probe could produce a ratiometric response to micromolar sulfide in buffer (pH = 7.4), exhibiting a significant enhancement in fluorescent emission ratio (F427/F552) and obvious visual phenomenon (orange to pink under visible light and yellow to blue under UV light). At the same time, this NBD-AAP probe also has excellent properties including high selectivity and low detection limit (0.19 µM). In addition, this probe has been successfully used for detecting the sulfide in actual samples (monosodium glutamate, beer, environmental water) and imaging in Daphnia magna. These results indicate that NBD-AAP has broad application prospects in sulfide detection and in vivo imaging studies.

19.
Hum Vaccin Immunother ; 16(1): 100-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31210561

RESUMO

Botulinum neurotoxins (BoNTs) are among the most toxic proteins. Vaccination is an effective strategy to prevent botulism. To generate a vaccine suitable for human use, a recombinant non-His-tagged isoform of the Hc domain of botulinum neurotoxin serotype E (rEHc) was expressed in Escherichia coli and purified by sequential chromatography. The immunogenicity of rEHc was evaluated in mice and dose- and time-dependent immune responses were observed in both antibody titers and protective potency. Then, the pilot-scale expression and purification of rEHc were performed, and its immunological activity was characterized. Our results showed rEHc has good immunogenicity and can elicit strong protective potency against botulinum neurotoxin serotype E (BoNT/E) in mice, indicating that rEHc is an effective botulism vaccine candidate. Further, we developed a novel antitoxin against BoNT/E by purifying F(ab')2 from pepsin-digested serum IgG of rEHc-inoculated horses. The protective effect of the F(ab')2 antitoxin was determined in vitro and in vivo. The results showed that our F(ab')2 antitoxin can prevent botulism in BoNT/E-challenged mice and effectively alleviate the progression of paralysis caused by BoNT/E to achieve therapeutic effects. Therefore, our results provide valuable experimental data for the production of a novel antitoxin, which is a promising candidate for the treatment of BoNT/E-induced botulism.

20.
Sci Total Environ ; 705: 135783, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31787299

RESUMO

Decabromodiphenyl ether (BDE-209) and its substitute decabromodiphenyl ethane (DBDPE) are heavily used in various industrial products as flame retardant. They have been found to be persistent in the environment and have adverse health effects in humans. Although some former studies have reported toxic effects of BDE-209, the study of DBDPE's toxic effects is still in its infancy, and the effects of DBDPE on hepatotoxicity are also unclear. This study aimed to evaluate and compare the hepatotoxicity induced by BDE-209 and DBDPE using a rat model. Sprague-Dawley rats were administered DBDPE or BDE-209 (5, 50, 500 mg/kg bodyweight) intragastrically once a day for 28 days. Twenty-four hours after the end of treatment, the rats were sacrificed, and body liver weight, blood biochemical parameters, liver pathology, oxidative stress, inflammation, pregnane X receptor (PXR), constitutive androstane receptor (CAR), and changes in cytochrome P450 (CYP3A) enzymes were measured. Our results showed that both BDE-209 and DBDPE could cause liver morphological changes, induce oxidative stress, increase γ-glutamyl transferase and glucose levels in serum, and down-regulate PXR, CAR, and CYP3A expression. In addition, BDE-209 was found to increase liver weight and the ratio of liver/body weight, lead to elevated total bilirubin and indirect bilirubin levels in serum, and induce inflammation. The present study indicated that BDE-209 and DBDPE may interfere with normal metabolism in rats through oxidative stress and inflammation, which inhibit PXR and CAR to induce the expression of CYP3A enzymes, and finally produce hepatotoxic effects and cause liver damage in rats. Comparatively, our results show that the damage caused by BDE-209 was more serious than that caused by DBDPE.

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