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1.
Food Chem ; 336: 127710, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32763739

RESUMO

Conventional gold nanoparticle-based lateral flow immunoassay (LFIA) usually suffers a huge challenge in measuring target concentration in food matrices with dark color because of its poor resistance to the background matrix and color interference. To address this issue, we first report a novel bifunctional magneto-gold nanohybrid (MGNH) for the simultaneous magnetic separation and colorimetric target sensing by integrating MGNHs into LFIA. Under optimum conditions, an ultrasensitive detection of ochratoxin A (OTA) in grape juice was achieved with a limit of detection at 0.094 ng mL-1. The average recoveries of this MGNH-LFIA ranged from 92.31% to 108.97% with a coefficient of variation of below 12%. The excellent selectivity of our MGNH-LFIA against OTA was demonstrated. Besides, our MGNH-LFIA is comparable to liquid chromatography coupled with mass spectrometry in terms of accuracy, reproducibility, and practicability. The designed MGNH-LFIA platform is readily extended for improving other small molecule detection in food samples.

2.
Chem Commun (Camb) ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034588

RESUMO

Supramolecular assemblies with reversible boronate ester linkages are facilely prepared via self-assembly between cyclodextrin-centered glycoclusters and 4,4'-(1,2-diphenylethene-1,2-diyl)bis(1,4-phenylene)diboronic acid (TPEDB). Such sphere-like assemblies have shown a typical aggregation-induced emission (AIE) effect and could act as fluorescent probes for the sensitive detection of phenols in water.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33023894

RESUMO

BACKGROUND AND OBJECTIVES: Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, double-blind, placebo-controlled phase 2 pilot trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted. RESULTS: Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF-α, IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups. CONCLUSIONS: This randomized phase 2 pilot trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888.

5.
Br J Cancer ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33024266

RESUMO

BACKGROUND: Our previous study demonstrated that lysine demethylase 2A (KDM2A) enhances stemness in breast cancer cells. This demethylase is also highly expressed in cancer-associated fibroblasts (CAFs). However, its clinical significance is unclear. METHODS: The expression of KDM2A in CAFs was studied using immunohistochemical staining and its association with clinicopathological features and patient's survival was tested. Overexpression and knockdown strategies were used to investigate KDM2A-regulated genes in fibroblasts. Senescent cells were detected by using ß-galactosidase staining. The in vivo tumour-promoting activity of stromal KDM2A was confirmed by animal study. RESULTS: Increase of stromal KDM2A is associated with advanced tumour stage and poor clinical outcome in breast cancer patients. Cancer-derived cytokines stimulated KDM2A expression in normal fibroblasts and transformed them into CAFs. Upregulation of KDM2A induced p53-dependent senescence in fibroblasts and enhanced the release of cytokines, which reciprocally promoted cancer cell proliferation. Additionally, KDM2A upregulated programmed death-ligand 1 (PD-L1) expression via transcriptional activation in fibroblasts. Knockdown of KDM2A completely abolished the tumour-promoting activity of CAFs on breast tumour growth in vivo and diminished PD-L1 expression in the stroma of tumour tissues. CONCLUSIONS: Stromal KDM2A plays an oncogenic role in breast cancer and inhibition of KDM2A reduces fibroblast senescence and suppresses tumour growth.

6.
Oncol Rep ; 44(5): 1917-1928, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000247

RESUMO

Paclitaxel (PXL) is a chemotherapeutic agent widely used in solid tumors. However, whether PXL causes premature ovarian insufficiency in women of reproductive age remains controversial. The aim of the present study was to answer how and for how long PXL affects fertility, and to identify the protective effect of gonadotropin­releasing hormone agonist (GnRHa) in mice. A single dose of PXL was administered to 7­week­old female ICR mice. Mice were treated with GnRHa for 1 estrous cycle prior to chemotherapy, and for another following chemotherapy. On the days 1, 6, 11 and 16 following the administration of PXL, mice were assessed by ovarian histology, ovarian stimulation and mating experiment. Multiple doses of PXL were also administered to verify the duration of the gonadotoxicity of PXL. It was determined that PXL only destroyed antral follicles on day 1 following chemotherapy without reducing primordial follicles. In vitro experiments revealed that PXL impaired oocytes in metaphase, excluding those at the germinal vesicle stage. The number and quality of retrieved metaphaseⅡ(MⅡ) oocytes in PXL­exposed mice were reduced on day 1 following chemotherapy, which was recovered on day 11. MⅡ oocytes from mice pretreated with GnRHa recovered on day 6 following chemotherapy. Following 3 estrous cycles in mice after the last dose of the 3­dose paclitaxel administration, follicles in all stages and retrieved MII oocytes were recovered. It was concluded that the impairment caused by PXL on follicles and oocytes in mice lasted for <3 estrous cycles, which was shortened by pretreatment of GnRHa.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1480-1485, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067941

RESUMO

OBJECTIVE: To investigate the correlation of NK cell receptor-interacting serine/threonine kinase 1(RIPK1) activity and expression with prognosis of acute myeloid leukemia (AML) patients with FLT3-ITD mutation. METHODS: A total of 132 AML patients with FLT3-ITD mutation and 136 AML patients with FLT3-WT were selected. Clinical data and the number, length and rearrangement ratio of FLT3-ITD mutations were collected. The ratio of CD4+ T cells, regulatory T cells(Tregs), CD8+ T cells, B cells, natural killer cells(NK cells) and macrophage in peripheral blood(PB) were analyzed by flow cytometry. Correlation of NK cell ratio with FLT3-ITD mutation number, length and rearrangement ratio was analyzed by Pearson correlation analysis. Western blot and RT-qPCR were used to detect RIPK1 protein and mRNA levels in NK cells, respectively. Plasma RIPK activity was detected by ELISA, and Pearson corre-lation analysis was performed for the correlation of RIPK with FLT3-ITD mutation number, length and rearrangement ratio. Kaplan-Meier curve was used to analyze the survival rate of AML patients with FLT3-ITD mutation. RESULTS: Compared with AML patients with FLT3-WT, the white blood cell count in patients with FLT3-ITD mutation significantly increased, PB and BM blasts significantly decreased. There was no significant change in PB CD3+ T cells, Tregs, CD8+ T cells, B cells, M1 and M2 type macrophage of AML patients with FLT3-WT and FLT3-ITD mutation;Compared with AML patients with FLT3-WT, CD4+ T cells significantly decreased, NK cells significantly increased in AML patients wtih FLT3-ITD mutation. NK cells ratio in AML patients with FLT3-ITD mutation significantly positively correlated with the number of FLT3-ITD mutations and rearrangement bases. Plasma RIPK1 activity, RIPK1 protein and mRNA levels in NK cells of AML patients with FLT3-ITD were significantly lower than those of AML patients with FLT3-WT, and negatively correlated with the number of FLT3-ITD mutations, the length of rearranged bases (≥52 bp) and the ratio of rearranged bases. The survival rate of AML patients with FLT3-ITD mutation in low RIPK1 activity after Rydapt treatment was significantly higher than that in high RIPK1 activity. CONCLUSION: The prognosis of AML patients with FLT3-ITD mutation closely relates with plasma RIPK1 activity and RIPK1 expression in NK cells.

8.
Int Immunopharmacol ; 89(Pt B): 107086, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068868

RESUMO

AIMS: The purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion (MI/R) injury. MAIN METHODS: C57BL/6 mice were exposed to puerarin (100 mg/kg) with or without the SIRT1 inhibitor nicotinamide (500 mg/kg) and then subjected to MI/R operation. Myocardial infarct size, serum creatine kinase-MB (CK-MB) activity, apoptotic cell death, and cardiac structure and function were examined to evaluate MI/R injury. RT-PCR and western blotting were used to determine the inflammatory response and inflammasome activation, as well as activation of SIRT1/NF-κB pathway. RESULTS: Puerarin significantly reduced myocardial infarct size, serum CK-MB activity, and apoptotic cell death, and improved cardiac structural damage and dysfunction. Moreover, puerarin notably decreased the mRNA and protein levels of TNF-α, IL-6, and IL-1ß, indicating that puerarin attenuated MI/R-induced inflammation. Furthermore, puerarin markedly decreased the protein levels of Ac-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1ß, and cleaved IL-18 and increased the protein level of SIRT1. More importantly, the SIRT1 inhibitor nicotinamide prevented these puerarin-induced cardioprotective effects and regulation of the SIRT1/NF-κB pathway, as well as the NLRP3 inflammasome activation. CONCLUSION: Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects. These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease.

10.
Transplant Proc ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33004221

RESUMO

Iliac atherosclerosis is common in renal transplant recipients. In severe cases, it affects intraoperative renal arterial anastomosis and increases the risk of postanastomosis complications. At present, safe and efficient vascular replacement methods are relatively limited. In the 2 renal transplant cases at our center, described here, the donors' iliac arteries were unavailable. We therefore attempted to replace the recipients' diseased external iliac artery with the donors' inferior vena cava and then performed an end-to-side grafting with the attachment in arterial reconstruction. One patient received a single kidney transplantation, while the other received a dual kidney transplantation. Antiplatelet/anticoagulation drug application was avoided, and both patients were observed for more than 6 months. Stable renal graft function was achieved without any vascular complications. During this study, all procedures were in compliance with the Helsinki Congress and the Declaration of Istanbul. For end-stage renal disease patients with severe iliac atherosclerosis who are waiting for kidney transplantation, a donor's vena cava graft could potentially be a promising replacement option to restore external iliac artery patency and reconstruct renal blood flow, without the necessity of harvesting a recipient's autologous vessels or looking for costly artificial ones.

11.
J Environ Qual ; 49(2): 358-367, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33016432

RESUMO

In this work, the use of a coupled process, alkyl glycoside (APG) enhanced soil desorption followed by the zero-valent iron-ethylenediaminetetraacetic acid (EDTA)-air (ZEA) Fenton-like system, was investigated for the remediation of a simulated hexachlorobenzene (HCB)-contaminated diatomite soil and a real HCB-contaminated soil. Three surfactants with different concentrations were studied to obtain the suitable soil desorption agent. Compared with APG0810 and Triton x-100, APG0814 showed a better solubilization effect due to its lower critical micelle concentration. With addition of 3000 mg L-1 APG0814, 35% of HCB was removed from contaminated diatomite soil, and a small amount of residual APG in diatomite soil was found to be beneficial for the soil dispersion. After treatment with the ZEA system, the removal efficiency of HCB in the diatomite soil desorption solution reached 76% in 2 h; we observed that a small amount of APG retained in the desorption solution accelerated the HCB removal. A real HCB-contaminated soil was used to verify the remediation effects. This study demonstrates that our approach is a feasible alternative for remediating soil contaminated with hydrophobic organic compounds.


Assuntos
Recuperação e Remediação Ambiental , Poluentes do Solo/análise , Ácido Edético , Glicosídeos , Hexaclorobenzeno , Ferro , Solo
12.
Genomics ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011328

RESUMO

Intermuscular bone (IB) is a hard-boned spicule exist in lower teleost, which brings a lot of detrimental effects on palatability and economic value of blunt snout bream (Megalobrama amblycephala). Masson trichrome staining for ossific IB indicated that some osteoblasts appeared at the edge of the bone matrix and a few osteocytes are present in the center of the mineralized bone matrix. By comparing the orthologous gene families of fish with IBs and without IBs, we screened the key signaling pathways associated with IB formation. Furthermore, the transcriptomic data demonstrated the functional importance of these gene families. The candidate genes involved in chondrocyte development were highly expressed in stage 1 compared with stage 2 and stage 3, suggesting that the development process of IB might mainly involve in intramembranous ossification. Our research reveals the molecular mechanism of IBs formation, and provides molecular evidence for the further study on intermuscular boneless stains.

13.
J Int Med Res ; 48(10): 300060520948337, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33045874

RESUMO

OBJECTIVE: Stress urinary incontinence (SUI) is prevalent worldwide, particularly among elderly women. Although electroacupuncture (EA) has been accepted by many patients and physicians in Asia, its efficacy for SUI has not been evaluated scientifically and systematically. We aimed to conduct a systematic evaluation of the efficacy and safety of EA treatment for women with SUI. METHODS: We retrieved publications up to February 2019 from seven databases. Randomized controlled trials for women with SUI treated by EA were included. Therapeutic effect, 1-hour urine leakage and International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) scores were the primary outcomes. The Cochrane Collection's RevMan 5.3 software was used to pool data. RESULTS: The 15 included articles demonstrated that EA for SUI was effective (odds ratio [OR], confidence interval [CI] = 5.64, 4.19-7.59; Ι2 = 22%). ICIQ-SF scores increased (standard mean difference, CI = -0.48, -0.62 to -0.33; Ι2 = 32%) and 1-hour urine leakage decreased (OR, CI = -4.14, -4.96 to -3.33; Ι2 = 78%) in patients undergoing EA compared with those receiving sham EA, physical exercise or medication. CONCLUSION: EA for women with SUI exhibited significant efficacy and safety for key outcomes.

14.
J Food Biochem ; : e13518, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047354

RESUMO

Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu Island, Taiwan. This present study aimed to investigate the protective effects of aqueous extract of Pepino leaves (AEPL) in mice with metabolic syndrome. Metabolic syndrome animal model was induced by continuous high-fat diet feeding and low-dose streptozotocin (40 mg/ml) for 5 days. A 1% AEPL or metformin were given for 6 weeks after streptozotocin injection. The results revealed that 1% AEPL effectively reduced fasting blood glucose, insulin resistance, and hyperlipidemia in metabolic syndrome mice. Histologic examination revealed lipid accumulation in liver decreased by 1% AEPL treatment. Further, western blot analysis revealed 1% AEPL treatment managed enzymes related to lipid synthesis and oxidation pathways and hepatic glucose production. Besides, 1% AEPL treatment increased liver antioxidant activities to against oxidative stress. These results concluded that AEPL treatment attenuated insulin resistance, hyperlipidemia, and hyperglycemia of metabolic syndrome. PRACTICAL APPLICATIONS: Metabolic syndrome (MS) is a multifactorial chronic disease which is characterized by dyslipidemia, insulin resistance, and hyperglycemia. However, there is no single drug or defined medication for MS so far. The present study revealed that AEPL treatment was able to regulate lipid metabolism and glycemic control at the molecular level to alleviate MS. AEPL has the potential to be a novo complementary medication for metabolic syndrome.

15.
Plant J ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048422

RESUMO

Ethylene is a key plant hormone controlling the ripening of climacteric fruits, and a few transcription factors acting as important regulators of fruit ripening have been identified in tomato (Solanum lycopersicum), a model for climacteric fruits. However, the vast majority of them are transcriptional activators, and the associated transcriptional regulatory mechanisms of most regulators are unclear. Here, we report on a tomato transcriptional repressor (termed SlMYB70) that negatively regulates fruit ripening by directly modulating ethylene biosynthesis. As an EAR motif-containing MYB transcription factor-encoding gene, SlMYB70 displayed a ripening-associated expression pattern and was responsive to ethylene. RNA interference (RNAi)-mediated repression of SlMYB70 accelerated fruit ripening, but overexpression of SlMYB70 delayed fruit ripening. Ethylene production was noticeably increased and decreased in SlMYB70-RNAi and SlMYB70-overexpressing lines, respectively, compared to wild-type tomatoes. SlMYB70 was proven to be a transcriptional repressor, dependent on the EAR repression motif, and to repress the transcription of two ethylene biosynthesis genes in fruit ripening, namely, SlACS2 and SlACO3. The promoters of SlACS2 and SlACO3 are directly bound by SlMYB70, which was verified by using a combination of yeast one-hybrid, chromatin immunoprecipitation-qPCR, and electrophoretic mobility shift assays. These results suggest that SlMYB70 negatively regulates fruit ripening via direct transcriptional repression of ethylene biosynthesis genes, which provides insights into the ethylene-mediated key regulatory hierarchy in climacteric fruit ripening and also highlights different types of transcriptional regulation of fruit ripening.

16.
Pediatr Hematol Oncol ; : 1-11, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016804

RESUMO

The standard chemotherapy for acute myeloid leukemia (AML) is usually composed of anthracyclines and cytarabine. We previously reported that homoharringtonine (HHT) was incorporated into regimens for pediatric AML with acceptable efficacy and tolerable toxicity. We treated newly diagnosed AML patients aged 0-18 years on the AML-SCMC-2009 protocol. A total of 102 de novo newly diagnosed AML patients aged 0-18 years were enrolled. All patients were treated with ten courses of chemotherapy including double induction, high dose cytarabine consolidation, and maintenance. The cumulative dose of HHT was 165 mg/m2 and the daunorubicin dose was 120 mg/m2. Complete remission (CR), overall survival (OS) rate, event free survival (EFS) rate, adverse effect response and prognosis factors were retrospectively evaluated to investigate the long-term outcome and safety of this protocol. Eighty-two patients (80.4%) achieved complete remission with the first induction. The 5-year overall survival and event-free survival rates were 65.0% (SE, 4.9%) and 53.3% (SE, 5.2%), respectively. A first induction failure, age older than 2 years, and BCR-ABL translocation were associated with a significantly worse outcome (p < 0.05). No significant drug-related cardiac toxicity was observed. AML-SCMC-2009 protocol which use HHT as backbone drug is efficacious and tolerated. HHT could partially replace anthracycline to be an effective option for childhood AML.

17.
Neurology ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999058

RESUMO

OBJECTIVE: To determine the effects of a 12-week home-based motor training telerehabilitation program in subcortical stroke patients by combing of motor function assessments and multimodality MRI analysis methods. METHODS: Fifty-two stroke patients with hemiplegia were randomly assigned to either a home-based motor training telerehabilitation (TR) group or a conventional rehabilitation (CR) group for 12 weeks. The Fugl-Meyer assessment (FMA) for upper and lower extremities and the modified Barthel index (MBI) were used as primary outcomes. The secondary outcomes included resting-state functional connectivity (rsFC) between the bilateral M1 areas, gray matter volumes of the primary motor cortex (M1) areas and white matter integrity of the corticospinal tract (CST). Analysis of covariance was applied to examine the effects of the home-based motor training TR program on neural function recovery and brain plasticity. RESULTS: Compared with the CR group, the TR group showed significant improvement in the FMA (P = 0.011) and significantly increased M1-M1 rsFC (P = 0.031) at the end of the rehabilitation. The M1-M1 rsFC change was significantly positively correlated with the FMA change in the TR group (P = 0.018). CONCLUSION: This study showed a beneficial effect of the home-based motor training telerehabilitation program on motor function in stroke patients, which was accompanied by enhanced interhemispheric functional connectivity of the M1 areas. We inferred that it is feasible, safe and efficacious for stroke patients to receive professional rehabilitation training at home. Additionally, the combined use of imaging biomarkers should be encouraged in motor training clinical studies in stroke patients. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for stroke patients with hemiplegia, home-based telerehabilitation compared to conventional rehabilitation significantly improves some motor function tests.

18.
Bioorg Chem ; 104: 104314, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33011538

RESUMO

Small molecule accurate recognition technology (SMART) is an emerging method for the rapid structural prediction of major constituents from crude extracts and fractions. In the present study, a targeted isolation of an Elephantopus scaber extract by SMART resulted in the obtention of 15 new (1-15) and five known germacranolide sesquiterpenes (16-20). Their structures were assigned by extensively analyzing HRESIMS, NMR, X-ray crystallographic analyses, modified Mosher's method results, and quantum chemical calculate electronic circular dichroism (ECD) spectra. All germacranolide sesquiterpenes were screened to determine their inhibitory effects with two hepatoma cell lines (HepG2 and Hep3B), and compounds 14, 16, 18, 19 and 20 showed significant cytotoxic activities against the HepG2 (IC50, 3.3-9.9 µM) and Hep3B (IC50, 4.5-8.6 µM) cell lines. Further study suggested that 18 can induce the apoptosis of hepatoma cells via mitochondrial dysfunction.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33030687

RESUMO

Epidemiological evidence of lung cancer risk from radon is based mainly on studies of underground miners where occupational exposures were, historically, relatively high in comparison to residential indoor exposure. However, radiation protection measures have caused radon levels in uranium mines to decrease significantly in more recent periods. Miners' occupational exposure is limited to their working years while they are exposed to environmental radon at home over their entire lifetime. Even during their limited working years, workers spend much more time at home than in workplaces. The biological effect of radon in mines cannot be distinguished from the biological effect of residential radon. Therefore, for an exposure-risk relationship study of former uranium miners, excess radon-induced lung cancer cases should be related to the combined radon exposure cumulated in workplaces and at homes in excess of the radon exposure of the reference population. This is especially important when residential radon levels differ or vary significantly between miners and the reference population over the course of extended follow-up years. This paper reviews some recent studies on former uranium miners, shares what seems controversial to the author and wonders whether lifetime exposure at home to widely varying radon concentrations can actually impact the quality of exposure assessment, and hence impact the results of the exposure-risk relationship.

20.
Environ Pollut ; 268(Pt B): 115733, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33011576

RESUMO

With numerous new chemicals introduced into the environment everyday, identification of their potential hazards to the environment and human health is a considerable challenge. Developing adverse outcome pathway (AOP) framework is promising in helping to achieve this goal as it can bring In Vitro testing into toxicity measurement and understanding. To explore the toxic mechanism underlying environmental chemicals via the AOP approach, an integration of adequate experimental data with systems biology understanding is preferred. Here, we describe a novel method to develop reliable and sensible AOPs that relies on chemical-gene interactions, toxicity pathways, molecular regulations, phenotypes, and outcomes information obtained from comparative toxicogenomics database (CTD) and Ingenuity Pathway Analysis (IPA). Using Benzo(a)pyrene (BaP), a highly studied chemical as a stressor, we identified the pivotal IPA toxicity pathways, the molecular initiating event (MIE), and candidate key events (KEs) to structure AOPs in the liver and lung, respectively. Further, we used the corresponding CTD information of multiple typical AHR-ligands, including 2,3,7,8-tetrachlorodibenzoparadioxin (TCDD), valproic acid, quercetin, and particulate matter, to validate our AOP networks. Our approach is likely to speed up AOP development as providing a time- and cost-efficient way to collect all fragmented bioinformation in published studies. It also facilitates a better understanding of the toxic mechanism of environmental chemicals, and potentially brings new insights into the screening of critical paths in the AOP network.

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