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1.
Adv Mater ; : e1908109, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022983

RESUMO

Photodynamic therapy (PDT) efficacy has been severely limited by oxygen (O2 ) deficiency in tumors and the electron-hole separation inefficiency in photosensitizers, especially the long-range diffusion of O2 toward photosensitizers during the PDT process. Herein, novel bismuth sulfide (Bi2 S3 )@bismuth (Bi) Z-scheme heterostructured nanorods (NRs) are designed to realize the spatiotemporally synchronous O2 self-supply and production of reactive oxygen species for hypoxic tumor therapy. Both narrow-bandgap Bi2 S3 and Bi components can be excited by a near-infrared laser to generate abundant electrons and holes. The Z-scheme heterostructure endows Bi2 S3 @Bi NRs with an efficient electron-hole separation ability and potent redox potentials, where the hole on the valence band of Bi2 S3 can react with water to supply O2 for the electron on the conduction band of Bi to produce reactive oxygen species. The Bi2 S3 @Bi NRs overcome the major obstacles of conventional photosensitizers during the PDT process and exhibit a promising phototherapeutic effect, supplying a new strategy for hypoxic tumor elimination.

2.
Theranostics ; 10(4): 1833-1848, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042339

RESUMO

Purpose: To determine the role of UCH-L1 in regulating ERα expression, and to evaluate whether therapeutic targeting of UCH-L1 can enhance the efficacy of anti-estrogen therapy against breast cancer with loss or reduction of ERα. Methods: Expressions of UCH-L1 and ERα were examined in breast cancer cells and patient specimens. The associations between UCH-L1 and ERα, therapeutic response and prognosis in breast cancer patients were analyzed using multiple databases. The molecular pathways by which UCH-L1 regulates ERα were analyzed using immunoblotting, qRT-PCR, immunoprecipitation, ubiquitination, luciferase and ChIP assays. The effects of UCH-L1 inhibition on the efficacy of tamoxifen in ERα (-) breast cancer cells were tested both in vivo and in vitro. Results: UCH-L1 expression was conversely correlated with ERα status in breast cancer, and the negative regulatory effect of UCH-L1 on ERα was mediated by the deubiquitinase-mediated stability of EGFR, which suppresses ERα transcription. High expression of UCH-L1 was associated with poor therapeutic response and prognosis in patients with breast cancer. Up-regulation of ERα caused by UCH-L1 inhibition could significantly enhance the efficacy of tamoxifen and fulvestrant in ERα (-) breast cancer both in vivo and in vitro. Conclusions: Our results reveal an important role of UCH-L1 in modulating ERα status and demonstrate the involvement of UCH-L1-EGFR signaling pathway, suggesting that UCH-L1 may serve as a novel adjuvant target for treatment of hormone therapy-insensitive breast cancers. Targeting UCH-L1 to sensitize ER negative breast cancer to anti-estrogen therapy might represent a new therapeutic strategy that warrants further exploration.

3.
Anal Chem ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32066237

RESUMO

Aberrant brown adipose tissue (BAT) metabolism is linked to obesity as well as other metabolic disorders. However, the paucity of imaging tools limits the study of in vivo BAT metabolism in animal models. The current work evaluated a heptamethine dye (CyHF-8) in living mice as a dual-modality BAT-avid molecular probe for two imaging approaches, including near-infrared fluorescence imaging (NIRF) and photoacoustic imaging (PAI). CyHF-8 exhibited favorable spectral properties in the near-infrared window (786/787/805 nm), and accumulated in the subcellular mitochondria of brown adipocytes. After intravenous injection of CyHF-8, NIRF and PAI were both capable of non-invasively detecting interscapular BAT at early timepoints in living mice. Quantitative analysis of NIRF and PAI images showed that CyHF-8 signals respond to dynamic BAT changes in mice stimulated by norepinephrine (NE) and in diabetic mice induced by streptozotocin (STZ). In summary, dual-modality NIRF/PAI probe CyHF-8 can be used for both NIRF and PAI to non-invasively assess BAT metabolism in living animals.

4.
Cancer Med ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052594

RESUMO

Recent studies have demonstrated that various long non-coding RNAs (lncRNAs) participate in the gastric cancer (GC) development and metastasis. Some lncRNAs exert their regulatory function by interacting with microRNAs. Here we identified a novel lncRNA RP11-81H3.2 that was highly expressed in the GC tissue and cell lines. RP11-81H3.2 knockdown significantly inhibited the proliferation, migration, and invasion of GC cells. Mechanistically, we demonstrated that RP11-81H3.2 directly interacted with miR-339 while miR-339 regulated the HNRNPA1 expression by targeting HRRNPA1 3'-UTR. RP11-81H3.2-miR-339-HNRNPA1 interaction network regulated the GC cell proliferation, migration, and invasion. Moreover, our results confirmed that RP11-81H3.2 knockdown suppressed the tumor growth of GC in a xenograft model in vivo. In summary, the results suggest that RP11-81H3.2 functions as an oncogene in GC and could be utilized as a promising diagnosis and therapeutic marker for GC treatment.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32006327

RESUMO

Watershed exposure caused by the use of pesticide in farmland has become a major environmental concern. Currently, there are two major approaches to quantify the watershed exposure: monitoring and modeling. Watershed monitoring is expensive, and short-term monitoring is difficult to be used to address potential long-term exposure variability. Model simulation is widely used because not only can it save time and efforts, but it can also simulate the environmental transport process of pesticide over a long time frame to better understand temporal variability. Research on application of commonly used pesticide exposure assessment models such as PRZM, RICEWQ on watershed scale has found that those models need to be coupled together with waterbody models to assess pesticide exposure at the watershed level, and they are applied on a single crop in targeted area within a watershed, failing to consider the diversity of regional and watershed cropping conditions. To address pesticide exposure assessment in different waterbodies after application on multiple crops within a watershed, this study coupled PRZM, RICEWQ, and SWAT models simultaneously in North Tiaoxi watershed. PRZM model and RICEWQ model were used to simulate the exposure of pesticides in dryland and rice paddies separately, and the pesticide masses through runoff, overflow, spray drift, and other routes simulated by the above two models were set as the input of SWAT model which could simulate hydrology and pollutant transport at watershed scale. Pesticide use, cropping, hydrology, and watershed data were collected, and parameterized for exposure modeling of carbaryl in the North Tiaoxi River after uses on orchard, corn, and rice within the watershed. Model predictions showed high degree of agreement between the simulated results and the field monitoring data. The coupled PRZM, RICEWQ, and SWAT model could simulate reasonably well pesticide exposures in waterbodies with applications on multiple crops within a watershed.

6.
Eur J Clin Nutr ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932742

RESUMO

BACKGROUND/OBJECTIVES: The results linking body iron stores to the risk of gestational diabetes mellitus (GDM) are conflicting. We aimed to measure the serum ferritin level of women in early pregnancy and evaluate the risk of GDM in a Chinese urban population. SUBJECTS/METHODS: In total, 851 pregnant women between 10 and 20 weeks of gestation took part in the prospective, observational study conducted. The women were divided into four groups by quartiles of serum ferritin levels (Q1-4). Their blood samples were collected and assayed for several biochemical variables at the beginning of the study, and the women were followed up with a 75-g oral glucose tolerance test at 24-28 weeks of gestation. RESULTS: The participants had an average serum ferritin concentration of 65.67 µg/L. GDM prevalence within each serum ferritin quartile was 9.4%, 14.6%, 18.8% and 19.3%, respectively, (P = 0.016). The odds ratio for GDM in the ferritin Q2-4 was 1.64 (CI: 0.90-2.99), 2.23 (CI: 1.26-3.96) and 2.31 (CI: 1.30-4.10), compared with Q1, respectively. This association persisted after adjusting for potential confounders factors. In addition, in Q4, pregnant women with a pre-pregnancy body mass index ≥24 kg/m2, maternal age ≤35 years old or haemoglobin≥ 110 g/L did have an increased risk of developing GDM. CONCLUSIONS: Elevated serum ferritin concentrations in early gestation are associated with an increased risk of GDM, especially in pregnant women who have a high baseline iron storage status with no anaemia or who are overweight/obese. Individual iron supplementation should be considered to minimize the risk of GDM.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31978250

RESUMO

ISSUE ADDRESSED: Australia's national cervical screening program has reduced rates of cervical cancer morbidity and mortality. However, these benefits have not been experienced by all women. A Cervical Cancer Screening Project was implemented with lay health educators to address inequitable screening access by women experiencing socio-economic disadvantage. METHODS: Resources and a training program were developed and piloted with the specialist homelessness services workforce in Sydney, NSW. Data was collected to inform their development and evaluation through interviews, focus groups, self-administered surveys and analysis of NSW Pap Test Register data. RESULTS: Women reported low familiarity with the term 'cervical screening'. They identified a good patient-doctor relationship, and seeing a female practitioner, as screening enablers. While the majority reported having cervical screening before, NSW Pap Test Register data showed only 74% had screened previously and of those, 69% were overdue. Homelessness service workers expressed interest in talking with clients about cervical screening, and reported increased knowledge and confidence following training. CONCLUSION: The homelessness sector is an appropriate venue to access women who are disadvantaged and under-screened. However, increasing workforce capacity to discuss screening does not lead to increased screening for women accessing these services. Further efforts are required. SO WHAT?: Access to cervical screening by women experiencing disadvantage remains a challenge. Sustained multi-faceted health promotion efforts are required to increase access. These should be informed by additional research exploring barriers and enablers for this group of women.

8.
Steroids ; 156: 108583, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31982422

RESUMO

Five undescribed ergostane-type C28 sterols, daturmetesides A-E (1-5), were isolated from the leaves of Datura metel L. The chemical structures of these new compounds were characterized through extensive spectroscopic analysis and comparison with literatures. Among them, the absolute structures of daturmetesides A and C were unambiguously determined by X-ray crystallography. The anti-inflammatory effect of daturmetesides A-E was all tested by measuring nitric oxide production in lipopolysaccharide-activated RAW264.7 cells. Daturmetesides A, C and D moderatelylowered the NO production with IC50 values ranging from 17.05 ± 0.35 to 24.88 ± 0.93 µM.

9.
J Cell Physiol ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31975378

RESUMO

The blood-testis barrier (BTB) separates the seminiferous epithelium into the apical and basal compartments. The BTB has to operate timely and accurately to ensure the correct migration of germ cells, meanwhile maintaining the immunological barrier. Testin was first characterized from primary Sertoli cells, it is a secretory protein and a sensitive biomarker to monitor junctions between Sertoli and germ cells. Till now, the functions of testin on BTB dynamics and the involving mechanisms are unknown. Herein, testin acts as a regulatory protein on BTB integrity. In vitro testin knockdown by RNAi caused significant damage to the Sertoli cell barrier with no apparent changes in the protein levels of several major tight junction (TJ), adhesion junction, and gap junction proteins. Also, testin RNAi caused the diffusion of two TJ structural proteins, occludin and ZO-1, diffusing away from the Sertoli cell surface into the cytoplasm. Association and colocalization between ZO-1 and occludin were decreased after testin RNAi, examined by Co-IP and coimmunofluorescent staining, respectively. Furthermore, testin RNAi induced a dramatic disruption on the arrangement of actin filament bundles and a reduced F-actin/G-actin ratio. The actin regulatory protein ARP3 appeared at the Sertoli cell interface after testin RNAi without its protein level change, whereas overexpressing testin in Sertoli cells showed no effect on TJ barrier integrity. The above findings suggest that besides as a monitor for Sertoli-germ cell junction integrity, testin is also an essential molecule to maintain Sertoli-Sertoli junctions.

10.
Plant Biotechnol J ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31975524

RESUMO

Kenaf is an annual crop that is widely cultivated as a source of bast (phloem) fibres, the phytoremediation of heavy metal-contaminated farmlands and textile-relevant compounds. Leaf shape played a unique role in kenaf improvement, due to the inheritance as a single locus and the association with fibre development in typical lobed-leaf varieties. Here we report a high-quality genome assembly and annotation for var. 'Fuhong 952' with 1078 Mbp genome and 66 004 protein-coding genes integrating single-molecule real-time sequencing, a high-density genetic map and high-throughput chromosome conformation capture techniques. Gene mapping assists the identification of a homeobox transcription factor LATE MERISTEM IDENTITY 1 (HcLMI1) gene controlling lobed-leaf. Virus-induced gene silencing (VIGS) of HcLMI1 in a lobed-leaf variety was critical to induce round (entire)-like leaf formation. Candidate genes involved in cell wall formation were found in quantitative trait loci (QTL) for fibre yield and quality-related traits. Comparative genomic and transcriptome analyses revealed key genes involved in bast fibre formation, among which there are twice as many cellulose synthase A (CesA) genes due to a recent whole-genome duplication after divergence from Gossypium. Population genomic analysis showed two recent population bottlenecks in kenaf, suggesting domestication and improvement process have led to an increase in fibre biogenesis and yield. This chromosome-scale genome provides an important framework and toolkit for sequence-directed genetic improvement of fibre crops.

11.
J Colloid Interface Sci ; 561: 762-771, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759559

RESUMO

Among diverse transition metal silicates (TMSs), cobalt silicate (Co2SiO4) and manganese silicate (MnSiO3) have been diffusely developed for electrode materials due to their high theoretical capacity, structural stability and simple synthetic process. In this work, Co2SiO4 nanobelts@MnSiO3 have been designed and synthesized as the enhanced electrode for high-performance hybrid supercapacitors. The one-dimensional (1D) Co2SiO4 nanobelts enhance their ability to transport electrons along the long axis, which allows current collection during the charge and discharge to improve electrochemical performances. The MnSiO3 coating can be a steady elastic buffer layer, which can protect the active materials during the charge and discharge in effect. What's more, the "core" and "shell" will both be a considerable offering to the total capacity. Sure enough, the capacitance value of Co2SiO4 nanobelts@MnSiO3 can achieve 309 F g-1 at 0.5 A g-1 accompanied by 64% capacitance retention after 10,000 cycles. And the hybrid supercapacitor (HSC) device assembled by Co2SiO4 nanobelts@MnSiO3 and activated carbon (AC) own an excellent capacitance of 384 mF cm-2 at 2 mA cm-2 accompanied by 57% capacitance retention after 2000 cycles. Meanwhile, the Co2SiO4 nanobelts@MnSiO3//AC HSC device's power density (P/W m-2) and energy density (E/Wh m-2) can reach to be 30 W m-2 and 0.77 Wh m-2, respectively. The unique and novel microstructure makes cobalt silicate and manganese silicate shine once again in excellent electrochemical performance.

12.
Haemophilia ; 26(1): 122-128, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31742836

RESUMO

INTRODUCTION: An increased bleeding tendency has been shown in female haemophilia carriers compared to healthy females. Bleeding assessment tools (BATs) have mainly been performed in western cultures. It is unclear how they perform in populations with different healthcare, health/wellness concepts and awareness, as well as family planning practices. AIM: To (a) describe and compare the bleeding symptoms in carriers with healthy females, particularly for bleeding after surgical abortion and intrauterine device (IUD) placement which are performed frequently for family planning in China; (b) quantify scores of International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) and Chinese-BAT (C-BAT) developed to include surgical abortion and IUD placement as separate categories in Chinese haemophilia carriers; (c) correlate bleeding scores (BS) with factor levels. METHODS: We conducted a multicentre, cross-sectional study on obligate haemophilia carriers and healthy controls using ISTH-BAT and C-BAT. RESULTS: We enrolled 125 haemophilia carriers and 106 controls. Carriers, compared to controls, had significantly higher median BS (3 vs 1 by both ISTH-BAT and C-BAT) and lower factor level (63.5 vs 101.8 IU/dL). Bleeding after surgical abortion and IUD placement was significantly associated with carrier status. Bleeding scores from neither ISTH-BAT nor C-BAT showed significant correlation with factor levels. CONCLUSION: Haemophilia carriers in China experienced abnormal bleeding. Unique to the Chinese carriers is significant bleeding after surgical abortion (3rd highest incidence of bleeding symptom) and IUD placement (4th highest). However, both ISTH-BAT and C-BAT exhibited no correlation between BS and factor levels in this population and neither could identify carriers with low factor level (of <50 IU/dL).

13.
J Pediatr Adolesc Gynecol ; 33(1): 33-38, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31648037

RESUMO

STUDY OBJECTIVE: To investigate the knowledge and beliefs regarding the use of intrauterine devices (IUDs) for nulliparous women among Chinese health care providers and assess the potential factors related to their misconceptions and conservative beliefs. DESIGN, SETTING, PARTICIPANT, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A self-administered survey was conducted at 2 Chinese national academic conferences in 2015. The questionnaire data obtained from 103 health care providers were analyzed to examine the providers' knowledge regarding the safety and effectiveness of IUDs and the complications associated with IUD use, as well as their beliefs regarding the suitability of IUDs for nulliparous women. An ordinal logistic regression model was used to evaluate the potential factors related to their beliefs. RESULTS: Misconceptions about the complications associated with IUD use were common among our respondents, and they were least likely to know that IUDs do not increase the risk of developing pelvic inflammatory disease (26/97) or ectopic pregnancy (23/102) (22.5%-26.8%). Only approximately 10% of the providers believed that adolescents (9/94) or unmarried nulliparas (10/95) could be candidates for IUDs. In contrast, they were more likely (37/96, 38.5%) to consider married nulliparous women as appropriate candidates (P < .001). Misconceptions about the complications of IUD use were associated with more conservative beliefs regarding IUD use for nulliparous women (adjusted odds ratio, 1.34; 95% confidence interval, 1.00-1.79). CONCLUSION: The health care providers' insufficient knowledge regarding IUDs contributed to their outdated and conservative beliefs about the suitability of IUDs for nulliparous women. In addition, the difference in the providers' beliefs regarding IUD use for married and unmarried nulliparous women might reflect the stigma associated with premarital sex in Chinese traditional culture.

14.
J Ethnopharmacol ; 248: 112262, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31585162

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

15.
Ecotoxicol Environ Saf ; 188: 109894, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706239

RESUMO

Modulation of plant salt tolerance has been drawing great attention. Thymol is a kind of natural chemical that has been developed as anti-microbial reagent and medicine. To date, we still have limited knowledge about thymol-modulated plant physiology. In this work, physiological, histochemical, and biochemical methods were adopted to study thymol-conferred salt resistance in the root of rice (Oryza sativa). Thymol significantly rescued root growth under salt stress. Thymol ameliorated cell membrane damage, oxidative stress, ROS accumulation, and cell death in roots under salt stress. Thymol-attenuated oxidative stress may be resulted from the activation of anti-oxidative capacity, including both enzymatic and non-enzymatic system. Thymol treatment significantly decreased Na+ content in root cells upon salt stress, which might be ascribed to the upregulation of OsSOS1 (salt overly sensitive 1) facilitating Na+ exclusion. In addition, thymol stimulated the expression of genes encoding tonoplast OsNHX (Na+/H+antiporter), which may help root cells to compartmentalize Na+ in vacuole. The results of these works evidenced that thymol was capable of inducing salt tolerance by reestablishing ROS homeostasis and modulating cellular Na+ flux in rice roots. These findings may be applicable to improve crop growth in salinity area.


Assuntos
Antioxidantes/metabolismo , Homeostase/efeitos dos fármacos , Oryza/efeitos dos fármacos , Tolerância ao Sal/efeitos dos fármacos , Sódio/metabolismo , Timol/farmacologia , Íons/metabolismo , Oryza/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plantas Tolerantes a Sal , Trocadores de Sódio-Hidrogênio/metabolismo
16.
Chemosphere ; 238: 124602, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545211

RESUMO

Polybrominated diphenyl ethers (PBDEs) have been known to exhibit neurotoxicity in rats; however, the underlying mechanism remains unknown and there is no available intervention. In this study, we aimed to investigate the role of oxidative and nitrosative stress in the neurotoxicity in the cerebral cortex and primary neurons in rats following the BDE-153 treatment. Compared to the untreated group, BDE-153 treatment significantly induced the neurotoxic effects in rats, as manifested by the increased lactate dehydrogenase (LDH) activities and cell apoptosis rates, and the decreased neurotrophic factor contents and cholinergic enzyme activities in rats' cerebral cortices and primary neurons. When compared to the untreated group, the oxidative and nitrosative stress had occurred in the cerebral cortex or primary neurons in rats following the BDE-153 treatment, as manifested by the increments in levels of reactive oxygenspecies (ROS), malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) mRNA and protein expressions, along with the decline in levels of superoxide dismutase (SOD) activity, glutathione (GSH) content, and peroxiredoxin I (Prx I) and Prx II mRNA and protein expressions. In addition, the ROS scavenger N-acetyl-l-cysteine (NAC) or NO scavenger NG-Nitro-l-arginine (L-NNA) significantly rescued the LDH leakage and cell survival, reversed the neurotrophin contents and cholinergic enzymes, mainly via regaining balance between oxidation/nitrosation and antioxidation. Overall, our findings suggested that oxidative and nitrosative stresses are involved in the neurotoxicity induced by BDE-153, and that the antioxidation is a potential targeted intervention.


Assuntos
Córtex Cerebral/patologia , Éteres Difenil Halogenados/toxicidade , Síndromes Neurotóxicas/patologia , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Acetilcisteína/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Glutationa/metabolismo , Éteres Difenil Halogenados/metabolismo , Masculino , Malondialdeído/metabolismo , Fatores de Crescimento Neural/metabolismo , Neurônios/efeitos dos fármacos , Neurotrofina 3/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Estresse Nitrosativo/fisiologia , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
17.
J Cell Physiol ; 235(1): 548-562, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31232471

RESUMO

Accumulating evidence implies that N6-methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression profile of seven m6A methylation-relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan-Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase-like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up-trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α-smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC.

18.
J Pharm Biomed Anal ; 180: 113045, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31887668

RESUMO

Nintedanib is a promising tyrosine kinase inhibitor for clinically treating idiopathic pulmonary fibrosis (IPF). Some clinical cases reported that nintedanib treatment can cause hepatotoxicity and myocardial toxicity. U. S. FDA warns the potential drug-drug interaction when it is co-administrated with other drugs. In order to understand the potential toxicity of nintedanib and avoid drug-drug interaction, the metabolism of nintedanib was systematically investigated in human liver microsomes and mice using metabolomics approach, and the toxicity of metabolites was predicted by ADMET lab. Nineteen metabolites were detected in vivo and in vitro metabolism, and 8 of them were undescribed. Calculated partition coefficients (Clog P) were used to distinguish the isomers of nintedanib metabolites in this study. The major metabolic pathways of nintedanib majorly included hydroxylation, demethylation, glucuronidation, and acetylation reactions. The ADMET prediction indicated that nintedanib was a substrate of the cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). And nintedanib and most of its metabolites might possess potential hepatotoxicity and cardiotoxicity. This study provided a global view of nintedanib metabolism, which could be used to understand the mechanism of adverse effects related to nintedanib and its potential drug-drug interaction.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31788950

RESUMO

Amorphous metal-organic frameworks (aMOFs) are an emerging family of attractive materials with great application potential, however aMOFs are usually prepared under harsh conditions and aMOFs with complex compositions and structures are rarely reported. In this work, an aMOF-dominated nanocomposite (aMOF-NC) with both structural and compositional complexity has been synthesized using a facile approach. A ligand-competition amorphization mechanism is proposed based on experimental and density functional theory calculation results. The aMOF-NC possesses a core-shell nanorod@nanosheet architecture, including a Fe-rich Fe-Co-aMOF core and a Co-rich Fe-Co-aMOF shell in the core-shell structured nanorod, and amorphous Co(OH)2 nanosheets as the outer layer. Benefiting from the structural and compositional heterogeneity, the aMOF-NC demonstrates an excellent oxygen evolution reaction activity with a low overpotential of 249 mV at 10.0 mA cm-2 and Tafel slope of 39.5 mV dec-1 .

20.
Microb Pathog ; 140: 103911, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31830580

RESUMO

Pasteurella multocida capsular type A can cause a pulmonary infection, leading to serious pecuniary losses in cattle. The heterogeneity of infection outcome of P. multocida strains showing different virulence may be related to divergent expression of virulence genes. In this study, we compared the transcriptional response of virulence-associated genes in high (PMPAN001) and low (PMPAN007) virulence P. multocida capsular type A strains in lung tissues and in vitro. These clinical isolates differ in their organ bacterial loads, mRNA abundance of the same virulence genes between lung and culture medium, and extent of lung damage. Among the eight virulence-associated genes (fimA, tbpA, exbD, fur, oma87, pmHAS, nanH, and tonB), seven genes showed higher expression in lung compared with in vitro at 16 h (P ≤ 0.05) in PMPAN001, but not in PMPAN007. FimA, exbD, fur, oma87, pmHAS, and tonB gene transcripts showed significantly higher expression in PMPAN001 than in PMPAN007 in the lung tissues at 16 h post-infection (P ≤ 0.05). Specially, the virulence gene, nanH, in both strains was associated with poor expression in vitro and lung tissue (mean relative mRNA abundance values < 0.6). Strain PMPAN001 had a higher proliferation rate in vivo than strain PMPAN007. The bacterial loads of PMPAN001 in the organs increased from 12 h post-infection, with maximum bacteria count ranging from 1 million to 20 million/mg. In addition, lungs treated with PMPAN001 produced serious and extensive lesions marked with inflammation at 20 h. Overall, our results reveal that the highly expressed virulence-associated genes, fimA, exbD, fur, oma87, pmHAS, and tonB can be used as markers for assessing the virulence of P. multocida capsular type A strains.

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