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1.
J Sci Food Agric ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953836

RESUMO

BACKGROUND: Thermal processing of food results in the formation of α-dicarbonyl compounds (α-DCs) such as glyoxal (GO), methylglyoxal (MGO), 2,3-butanedione (2,3-BD) and 3-deoxyglucosone (3-DG), which are precursors of potentially harmful advanced glycation end products. Some of the α-DCs found in food products might result from chemical deterioration reactions during storage and reheating. A range of sugary food simulation systems were stored at three different temperatures (4 °C, 25 °C and 37 °C) and reheated using three different processing methods to investigate the formation and migration of α-DCs. RESULTS: During 20 days of storage, the concentration of α-DCs declined, following which the concentration remained approximately constant. MGO was the major α-DCs affected during storage, its relative content being decreased from 233.71 µg/mL to 44.12 µg/mL in the glucose-lysine system. The concentration of α-DCs decreased with increasing temperature. Microwave reheating increased the formation of α-DCs compounds. The largest increases in 3-DG concentrations were observed in the maltose-lysine systems (24.94 to 35.74 µg/mL). The concentration of α-DCs had small difference in response to reheating at 100 °C, but declined when reheated at 150 °C. CONCLUSION: The concentration of α-DCs following storage and reheating depends on the type of sugar, lysine content, temperature, and method of reheating. This article is protected by copyright. All rights reserved.

2.
Theranostics ; 10(1): 300-311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903121

RESUMO

Metastasis is one of the most important factors that lead to poor prognosis in cancer patients, and effective suppression of the growth of primary cancer cells in a metastatic site is paramount in averting cancer progression. However, there is a lack of biomimetic three-dimensional (3D) in vitro models that can closely mimic the continuous growth of metastatic cancer cells in an organ-specific extracellular microenvironment (ECM) for assessing effective therapeutic strategies. Methods: In this metastatic tumor progression model, kidney cancer cells (Caki-1) and hepatocytes (i.e., HepLL cells) were co-cultured at an increasing ratio from 1:9 to 9:1 in a decellularized liver matrix (DLM)/gelatin methacryloyl (GelMA)-based biomimetic liver microtissue in a microfluidic device. Results: Via this model, we successfully demonstrated a linear anti-cancer relationship between the concentration of anti-cancer drug 5-Fluorouracil (5-FU) and the percentage of Caki-1 cells in the co-culture system (R2 = 0.89). Furthermore, the Poly(lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG)-based delivery system showed superior efficacy to free 5-FU in killing Caki-1 cells. Conclusions: In this study, we present a novel 3D metastasis-on-a-chip model mimicking the progression of kidney cancer cells metastasized to the liver for predicting treatment efficacy. Taken together, our study proved that the tumor progression model based on metastasis-on-a-chip with organ-specific ECM would provide a valuable tool for rapidly assessing treatment regimens and developing new chemotherapeutic agents.

3.
J Sep Sci ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919992

RESUMO

Curcumin widely exists in food, and rapid selective and accurate detection of curcumin have great significance in chemical industry. In this experiment, a new magnetic biocompatibility molecularly imprinted polymer was prepared with non-toxic and biocompatible Zein to adsorb curcumin selectively. The polymer has high biocompatibility, good adsorption capacity, and specific adsorption for curcumin. Combined with portable electrochemical workstations, the polymer can be used to detect curcumin rapidly and cost-effectively. Using curcumin as a template and Zein as the crosslinking agent, the polymers were synthesized on the surface of Fe3 O4 particles for solid phase extraction. The experimental results showed that the polymer reached large adsorption capacity (32.12 mg/g) with fast kinetics (20 mins). The adsorption characteristic of the polymer followed the Langmuir isotherm and pseudo-second-order kinetic models. Hexacyanoferrate was used as electrochemical probe to generate signals, and the linear range was 5-200 ug/mL for measuring curcumin. The experimental analysis showed that the polymer were an ideal material for selective accumulation of curcumin from complex samples. This approach has been successfully applied to the determination of curcumin in food samples with electrochemical detection, indicating that this is a feasible and practical technique. This article is protected by copyright. All rights reserved.

4.
Mater Sci Eng C Mater Biol Appl ; 108: 110189, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924023

RESUMO

Particulate pollution in the air has strong links with increased morbidity of cardiopulmonary diseases. Iron is one of the major carcinogens in air pollution and can produce hydroxyl radical which induce oxidative stress, lead to cell damage and even to cancer. In this work, a novel nitronyl nitroxide radical NITPh(OMe)2 (2-(2,4-dimethoxyphenyl) -4,4,5,5- tetramethylimidazoline- 1- oxyl-3- oxide) was prepared and characterized by electron spin-resonance spectroscopy (ESR), X-ray crystal diffraction, Fourier transform infrared (IR), X-ray powder diffraction (XRD), elemental analysis, ultraviolet and visible spectra (UV-Vis), and the electronic transition processes was also calculated by time-dependent density functional theory (TDDFT) to analysis UV-Vis spectrum. In vitro cell model of oxidative damage was established by ferric ammonium citrate (FAC) overload, and NITPh(OMe)2 was studied as a free radical scavenger to protect peroxidation of A549 cells. Results showed that NITPh(OMe)2 could significantly alleviate the damage of A549 cells by iron overload in cell morphology, cell viability, cell proliferation and cell apoptosis. The apoptotic signaling pathway of A549 cells induced by FAC and the protection mechanism of NITPh(OMe)2 were all discussed through the expression of three relating proteins, Bcl-2, Bax and DDIT3. This work confirms that nitroxide radicals are effective antioxidants, and have potential application in clinical practice as therapeutic agents.

5.
Acta Pharmacol Sin ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911637

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life-threatening monogenetic diseases characterized by progressive enlargement of fluid-filled renal cysts. Our previous study has shown that Ganoderma triterpenes (GT) retards PKD renal cyst development. In the present study we identified the effective ingredient of GT in suppression of kidney cyst development. Using an in vitro MDCK cystogenesis model, we identified ganoderic acid A (GA-A) as the most promising candidate among the 12 ganoderic acid (GA) monomers. We further showed that GA-A (6.25-100 µM) significantly inhibited cyst growth in MDCK cyst model and embryonic kidney cyst model in vitro, and the inhibitory effect was reversible. In kidney-specific Pkd1 knockout (kPKD) mice displaying severe cystic kidney disease, administration of GA-A (50 mg· kg-1 ·d-1, sc) significantly attenuated renal cyst development. In both MDCK cells and kidney of kPKD mice, we revealed that GA-A dose-dependently downregulated the Ras/MAPK signaling pathway. The expression of proliferating cell nuclear antigen (PCNA) was also suppressed, suggesting a possible effect of GA-A on cell proliferation. These experimental data suggest that GA-A may be the main ingredient of GT as a potential therapeutic reagent for treating ADPKD.

6.
Int J Mol Sci ; 21(1)2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31906428

RESUMO

Although prevalent in the determination of protein structures; crystallography always has the bottleneck of obtaining high-quality protein crystals for characterizing a wide range of proteins; especially large protein complexes. Stable fragments or domains of proteins are more readily to crystallize; which prompts the use of in situ proteolysis to remove flexible or unstable structures for improving crystallization and crystal quality. In this work; we investigated the effects of in situ proteolysis by chymotrypsin on the crystallization of the XcpVWX complex from the Type II secretion system of Pseudomonas aeruginosa. Different proteolysis conditions were found to result in two distinct lattices in the same crystallization solution. With a shorter chymotrypsin digestion at a lower concentration; the crystals exhibited a P3 hexagonal lattice that accommodates three complex molecules in one asymmetric unit. By contrast; a longer digestion with chymotrypsin of a 10-fold higher concentration facilitated the formation of a compact P212121 orthorhombic lattice with only one complex molecule in each asymmetric unit. The molecules in the hexagonal lattice have shown high atomic displacement parameter values compared with the ones in the orthorhombic lattice. Taken together; our results clearly demonstrate that different proteolysis conditions can result in the generation of distinct lattices in the same crystallization solution; which can be exploited in order to obtain different crystal forms of a better quality.

7.
Sci Total Environ ; 706: 136086, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855650

RESUMO

Recently, biochar is widely used as a soil amendment to improve soil properties, which might affect the fate and behavior of contaminants in soil. In this study, we investigated the effect of biochar on the migration of tetracycline (TC) in soil and their combined impacts on microbiome. Due to the strong interaction between soil and TC, adsorption, rather than photolysis or biodegradation, was the dominating dissipation way of TC in soil. Moreover, biochar could promote the vertical migration of TC through the decreased soil bulk density and its lower adsorption capacity. After 90-day incubation, only slight impact of TC on soil bacterial community was observed due to the rapid dissipation of TC in soil, whereas more available C supply induced by biochar significantly altered bacterial community via the enhancement of copiotrophic bacteria. Besides, biochar could decrease the soil pH and thus change the composition of fungal community. The effect of TC on fungal community was partially counteracted by biochar, which could adsorb part of TC and thus decrease the contact of TC with microorganisms. This work will improve our understanding of the fate of organic pollutants and evolution of microbiome in soil where biochar servers as soil amendment.

8.
Nature ; 577(7788): 121-126, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31853060

RESUMO

Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by 'reader' proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatin-reader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.

9.
Food Chem ; 308: 125584, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31654976

RESUMO

The influence of cropping systems on nutrition and food safety is controversial. This study aimed to evaluate the effects of an organic cropping system (OCS) on wheat nutrition and food safety at the molecular level by using a comprehensive research method. Nutrient deviation in samples from an OCS and a conventional cropping system (CCS) were detected, and 58 biomarkers were selected through multivariate statistical analysis and were further qualitatively and quantitatively analyzed. The health risk of heavy metal(loid)s (HMs) for different populations was assessed based on the estimated average daily dose and recommended ingestion reference dose, which indicated that populations ingesting grains from OCSs had higher non-carcinogenic and carcinogenic risks. Additionally, HMs posed greater non-carcinogenic risks to children under five years old and greater carcinogenic risks to adults.This study highlights the need to consider the potential risk from HMs and nutritive ingredient differences in organic food.


Assuntos
Triticum/química , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Metais Pesados/análise , Valor Nutritivo
10.
Int Braz J Urol ; 46(1): 70-80, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31851461

RESUMO

OBJECTIVE: To analyze the compositions of upper urinary tract stones and investigate their distributions in different gender and age groups. MATERIALS AND METHODS: Patients diagnosed with upper urinary tract stone disease between December 2014 and March 2018 were retrospectively reviewed. Patient's age, gender, BMI, comorbidities, stone event characteristics, and compositions were collected, and proportions of stone components in different gender and age groups were analyzed. RESULTS: A total of 1532 stone analyses were performed (992 from males and 540 from females). The mean age was younger in males (p<0.001). Males included more cases with larger BMI, hyperuricemia, and obesity, while females had more urinary tract infections. Multiple components were present in 61.8% of stones. Calcium oxalate (CaOx) (67.0%) was the most common component, followed by uric acid (UA) (11.8%), infection stone (11.4%), calcium phosphate (CaP) (8.0%), cystine (1.1%), brushite (0.4%), and 2,8-dihydroxyadenine (0.2%). Men contributed with more CaOx stones than women at age 30-49 years (all p<0.01) and more UA stones at 30-59 years (all p<0.05). Women contributed with more infection stones than men in age groups 30-49 and 60-69 years (all p<0.05), and more CaP stones at 30-49 years. The prevalence peak was 50-59 years in men and 60-69 years in women. Both genders had the lowest prevalence in adolescence. Prevalence of UA stones increased while that of infection stones decreased with aging in both genders. CONCLUSIONS: Age and sex had a strong association with distribution of stone compositions in this Chinese cohort.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31877011

RESUMO

In recent years, rapid development of induced pluripotent stem cell (iPSC) technology has provided good technical support for the study of human cardiovascular disease (CVD). In this work, a mimetic cell membrane and drug carrier OPFL system containing photoactive oligo(p-phenylene vinylene) functionalized with phospholipid units (OPV-lipid) was prepared for functional regulation of iPSC-derived cardiomyocytes. OPFL bound to the cell membrane of iPSC-derived human cardiomyocytes and significantly enhanced delivery of cyclosporin A (CsA) into these cells, which promoted the regulation of mitochondrial calcium levels and membrane potential by CsA. This led to the protection of the mitochondrial structure and function, thus reducing apoptosis of iPSC-derived cardiomyocytes and achieving the effect of treating CVD. OPFL not only acts as a fluorescent probe for cell imaging and visualization of the drug delivery process but also provides a tool to deliver lipid-insoluble drugs throughout the cell membrane. Benefiting from good biocompatibility, facile operation, and a visible and controllable cell uptake process, OPFL has good potential to be a powerful tool in future basic and clinical research applications involving iPSCs.

12.
Curr Mol Med ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808386

RESUMO

OBJECTIVE: To Investigate The Relationship Between Genetic Polymorphisms Of Rxrg Rs1467664, Rs3753898 And The Genetic Susceptibility Of Type 2 Diabetes In Chinese Han Population From South China. METHODS: In Our Case-Control Study, Single-Nucleotide Polymorphisms (Snps) Rs1467664 And Rs3753898 Were Genotyped By Snpscantm Kit In 1092 Patients With T2d As Cases And 1092 Normal Persons As Controls. The Distributions Of Genotype And Allele Frequencies In Two Groups Was Analyzed By Spss 20.0 Software. RESULTS: The Distribution Of Genotypes And Alleles Of Rxrg Rs3753898 Was Statistically Significant Between Two Groups, But There Was No Significant Difference In The Distribution Of Genotypes And Alleles Of The Rs1467664. Before And After The Adjustment Of Age, Sex And Bmi, Rs3753898 In The Two Groups Had Statistical Significance Under The Additive, Dominant And Recessive Models (P<0.05), But No Statistical Differences Were Found Under The Overdominance And Co-Dominant Genetic Models (P>0.05). There Was No Significant Difference In The Genetic Models Of Rs1467664 Between The Two Groups (P>0.05). The Haplotype Which Consists Of Rs1467664 Allele T And Rs3753898 Allele A Was A High Risk Factor For T2d, Or=1.27, 95% Ci (1.09-1.47), Padj=0.002. CONCLUSION: Our Results Showed That The Single Nucleotide Polymorphism Of Rxrg Rs3753898 May Be Related To The Genetic Susceptibility Of Type 2 Diabetes. The Haplotype Consisting Of The Allele T Of Rs1467664 And The Allele A Of Rs3753898 Is A Risk Factor For Type 2 Diabetes, Suggesting That Genetic Variation Of Rxrg Gene May Be The Genetic Cause Of Diabetes Mellitus In Chinese Han Population.

13.
PLoS Comput Biol ; 15(12): e1007311, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31809500

RESUMO

The goal of many single-cell studies on eukaryotic cells is to gain insight into the biochemical reactions that control cell fate and state. In this paper we introduce the concept of Effective Stoichiometric Spaces (ESS) to guide the reconstruction of biochemical networks from multiplexed, fixed time-point, single-cell data. In contrast to methods based solely on statistical models of data, the ESS method leverages the power of the geometric theory of toric varieties to begin unraveling the structure of chemical reaction networks (CRN). This application of toric theory enables a data-driven mapping of covariance relationships in single-cell measurements into stoichiometric information, one in which each cell subpopulation has its associated ESS interpreted in terms of CRN theory. In the development of ESS we reframe certain aspects of the theory of CRN to better match data analysis. As an application of our approach we process cytomery- and image-based single-cell datasets and identify differences in cells treated with kinase inhibitors. Our approach is directly applicable to data acquired using readily accessible experimental methods such as Fluorescence Activated Cell Sorting (FACS) and multiplex immunofluorescence.

14.
Sci Rep ; 9(1): 18012, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784649

RESUMO

Tuberculosis (TB) disease still kills 1-person every 21-seconds. Few TB diagnostic tests are considered truly appropriate for point of care settings. The WHO-endorsed immunodiagnostic Alere Determine Lipoarabinomannan Ag-test (LAM-test) detects Mycobacterium tuberculosis complex LAM in urine, and its use is recommended for TB diagnosis among HIV co-infected individuals with low CD4 T-cell counts. Here we found that a simple 15-minute enzymatic treatment at room temperature of LAM-spiked urine with α-mannosidase (for human TB), and LAM-spiked milk with combined lactase and caseinase (for bovine TB), enhanced 10-fold the detection levels of the LAM-test and thus, improved the detection of LAM by the LAM-test in urine and milk that otherwise could be missed in the field. Future separate clinical research studies specifically designed to address the potential of these findings are required.

15.
Chin J Nat Med ; 17(11): 803-821, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31831128

RESUMO

Gui-Zhi-Jia-Ge-Gen-Tang (GZJGGT) is a traditional Chinese medicine (TCM) prescription commonly used to treat cervical spondylopathy, scapulohumeral periarthritis, etc. Though it is widely applied in clinical practice, the effective constituents of GZJGGT remain unclear. This was the first report on the identification of the chemical constituents from GZJGGT in vitro and in vivo using LC-IT-MS combined with LC-Q-TOF-MS. A total of 141 constituents were detected in GZJGGT, and 77 were identified. These compounds mainly included flavonoid glycosides, triterpene saponins, monoterpene glycosides, puerosides, and organic acids. Among them, 12 compounds were unequivocally identified in comparison with reference substances. Additionally, a diagnostic base peak ion filtering strategy for rapid classification of flavonoid O-glycosides and C-glycosides was proposed. After gastrointestinal administration of GZJGGT to rats, 45 prototypes and 48 metabolites in rat plasma were speculated. In addition, the metabolic profile of GZJGGT was portrayed to understand interrelationship between metabolites.

16.
J Pain Res ; 12: 3127-3133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814754

RESUMO

Purpose: Our study aims to investigate the distribution of pain symptoms and the association between pain symptoms and clinical parameters in patients with adenomyosis. Patients and methods: The clinical and pathological data of 291 patients diagnosed with adenomyosis in the Obstetrics and Gynecology Department of Peking Union Medical College Hospital from March 2012 to September 2015 were collected, and analyzed in regard to the pain symptoms. Results: The median age at disease onset was 34 years. 71.8% of the patients had pain symptoms (pain group) and 28.2% had no pain symptoms (painless group). Patients with symptoms accompanied by dysmenorrhea accounted for 68%, among which 30.3% were mild, 36.9% were moderate, and 32.8% severe, while 56.1% presented with progressive pain. Through comparison, significant differences were identified between the pain and painless groups with regard to age at diagnosis (P=0.009), age at onset of disease (P=0.008), and level of pre-surgical CA125 (P<0.001), as well as proportion of patients with rectal irritation (P=0.008), elevated CA125 level (P<0.001), thickened myometrial layer (P<0.001) and concurrent endometriosis (P=0.001). In the multivariable analysis, an elevated level of pre-surgical CA125 (P<0.001) and thickened posterior myometrial layer (P=0.023) were both independent risk factors for the morbidity of pain symptoms. Similar results except for the difference in rectal irritation were noticed when we made further comparison between the dysmenorrhea and non-dysmenorrhea groups in adenomyosis patients. Conclusion: Our research analyzes the clinical features related to pain symptoms in patients with adenomyosis, which may provide clues for the possible presurgical diagnosis of adenomyosis, as well as references for pain management of adenomyosis.

17.
Int Immunopharmacol ; 78: 106047, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31816576

RESUMO

Isosteroid alkaloids, natural products from Fritillariae Cirrhosae Bulbus, are well known for its antitussive, expectorant, anti-asthmatic and anti-inflammatory properties. However, the anti-inflammatory effect and its mechanism have not been fully explored. In this study, the anti-inflammatory activitives and the potential mechanisms of five isosteroid alkaloids from F. Cirrhosae Bulbus were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. The pro-inflammatory mediators and cytokines were measured by Griess reagent, ELISA and qRT-PCR. The expression of MAPKs was investigated by western blotting. Treatment with the five isosteroid alkaloids in appropriate concentrations could reduce the production of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in supernatant, and suppressed the mRNA expressions of TNF-α and IL-6. Meanwhile, the five isosteroid alkaloids significantly inhibited the phosphorylated activation of mitogen activated protein kinase (MAPK) signaling pathways, including extracellular signal-regulated kinase (ERK1/2), p38 MAPK and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). These results demonstrated that isosteroid alkaloids from F. Cirrhosae Bulbus exert anti-inflammatory effects by down-regulating the level of inflammatory mediators via mediation of MAPK phosphorylation in LPS-induced RAW264.7 macrophages, thus could be candidates for the prevention and treatment of inflammatory diseases.

18.
Environ Health ; 18(1): 107, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818305

RESUMO

BACKGROUND: Although no human illness to date is confirmed to be attributed to engineered nanoparticles, occupational epidemiological studies are needed to verify the health effects of nanoparticles. This study used a repeated measures design to explore the potential adverse health effects of workers handling nanomaterials. METHODS: Study population was 206 nanomaterial-handling workers and 108 unexposed controls, who were recruited from 14 nanotechnology plants. They were followed up no less than two times in four years. A questionnaire was used to collect potential confounders and detailed work conditions. Control banding was adopted to categorize risk level for each participant as a surrogate marker of exposure. Health hazard markers include cardiopulmonary dysfunction markers, inflammation and oxidative damage markers, antioxidant enzymes activity, and genotoxicity markers. The Generalized Estimating Equation model was applied to analyze repeated measurements. RESULTS: In comparison to the controls, a significant dose-dependent increase on risk levels for the change of superoxide dismutase (p<0.01) and a significant increase of glutathione peroxidase change in risk level 1 was found for nanomaterial-handling workers. However, the change of cardiovascular dysfunction, lung damages, inflammation, oxidative damages, neurobehavioral and genotoxic markers were not found to be significantly associated with nanomaterials handling in this panel study. CONCLUSIONS: This repeated measurement study suggests that there was no evidence of potential adverse health effects under the existing workplace exposure levels among nanomaterials handling workers, except for the increase of antioxidant enzymes.

19.
Nat Immunol ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31819256

RESUMO

Ptpn6 is a cytoplasmic phosphatase that functions to prevent autoimmune and interleukin-1 (IL-1) receptor-dependent, caspase-1-independent inflammatory disease. Conditional deletion of Ptpn6 in neutrophils (Ptpn6∆PMN) is sufficient to initiate IL-1 receptor-dependent cutaneous inflammatory disease, but the source of IL-1 and the mechanisms behind IL-1 release remain unclear. Here, we investigate the mechanisms controlling IL-1α/ß release from neutrophils by inhibiting caspase-8-dependent apoptosis and Ripk1-Ripk3-Mlkl-regulated necroptosis. Loss of Ripk1 accelerated disease onset, whereas combined deletion of caspase-8 and either Ripk3 or Mlkl strongly protected Ptpn6∆PMN mice. Ptpn6∆PMN neutrophils displayed increased p38 mitogen-activated protein kinase-dependent Ripk1-independent IL-1 and tumor necrosis factor production, and were prone to cell death. Together, these data emphasize dual functions for Ptpn6 in the negative regulation of p38 mitogen-activated protein kinase activation to control tumor necrosis factor and IL-1α/ß expression, and in maintaining Ripk1 function to prevent caspase-8- and Ripk3-Mlkl-dependent cell death and concomitant IL-1α/ß release.

20.
Environ Res ; : 108902, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31785779

RESUMO

BACKGROUND: Phthalic acid esters are established as endocrine disruptors. The study aimed to evaluate the association between urinary phthalate metabolites and prostate cancer occurrence. METHODS: The study was based on the Taiwan Community-Based Cancer Screening Program, which was set up in 1991-1992 and followed periodically. By 2010, 80 incident prostate cancer cases were identified in the 12,020 men. For each case, 2 controls were randomly selected, matched by age (±3 years), urine collection date (±3 months), and residential township. Frequently used phthalate metabolites from the urine samples were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Logistic regression was conducted to assess the association between the exposure levels and prostate cancer occurrence. RESULTS: Exposure to di (2-ethylhexyl), butyl-benzyl and di-isobutyl phthalates (DEHP, BBzP, DiBP) was positively associated with prostate cancer in men with waist circumference (WC) ≥90 cm but not in the leans. Odds ratio for the DEHP metabolite summary score (upper tertile compared to the rest) and prostate cancer were 7.76 (95% CI = 1.95-30.9) for WC ≥ 90 cm. CONCLUSIONS: DEHP, BBzP, and DiBP exposure were associated with prostate cancer occurrence in abdominally obese men. The main limitation remains the lack of mechanistic experiments and comparable toxicological data.

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