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1.
J Nanosci Nanotechnol ; 20(2): 692-700, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383064

RESUMO

Fluorescent bimetallic Au-Ag nanoclusters (Au-AgNCs) were found to exhibit oxidase-like activity and could catalyze the oxidation of 3,3',5,5' tetramethylbenzidine (TMB) to oxTMB. On the basis of this property, we assembled a fluorescent nanoplatform as a turn-on probe for sensing mercury (II) ions (Hg2+) through the inner-filter effect (IFE). Au-AgNCs and oxTMB were chosen as IFE absorber and fluorophore pair for the first time. In the absence of Hg2+, the Au-AgNCs absorption band well. Covered the fluorescence emission band of oxTMB, and as a result, the fluorescence of oxTMB was reduced. In the presence of Hg2+, Hg2+ was reduced to Hg0 by extra BSA in Au-AgNCs probe system and anchored on the surface of Au-AgNCs. The absorption intensity for Au-AgNCs then decreased at 418 nm, resulting in the recovery of fluorescence from oxTMB. The formed Au-Hg thin amalgam layer obviously enhanced the oxidase-like activity of Au-AgNCs as well as hindered the IFE activity between Au-AgNCs and oxTMB. Therefore, based on the Hg2+ stimulating oxidaselike properties of Au-AgNCs, a fluorometric assay for determination of Hg2+ was developed in this study. The proposed sensing strategy showed a linear range from 10 nM to 500 nM, with ultralow LOD of ~0.7 nM for Hg2+. Moreover, the detection probe system was stable over a wide pH range, making it able to be applied in complex sample systems. We have successfully demonstrated the detection of Hg2+ in tap water samples. The fluorescent assay reported here, for sensitive and selective determination of Hg2+, may find great application in multiple areas, such as environmental and pharmaceutical analysis.

2.
J Nanosci Nanotechnol ; 20(1): 433-441, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383190

RESUMO

The production of p-type silicon/intrinsic ultrananocrystalline diamond/n-type nanocrystalline iron disilicide heterojunction devices was conducted via coaxial arc plasma deposition and pulsed laser deposition. The results of current density-voltage (J-V) curves justified a large leakage current along with minimal response under illumination. A recombination process controls the mechanism for carrier portage in the zone of V ≤ 0.16 V, while a space-charge-limited current process governs the carrier portage mechanism in the circumstance of V value beyond 0.16 V. Frequency (f) dependent conductance (G/ω)-V and capacitance (C)-V curves were measured to extract the series resistance (Rs) and density of the interface state (nss). On the basis of extraction in the manner of Nicollian-Brews, the value of Rs rose with f abatement. With zero bias voltage applied, the value of Rs was 189.84 Ω at 2 MHz and rose to 715.10 Ω at 20 kHz. The acquired Rs may be attributable to the occurrence of Rs in the neutral zones as well as Ohmic contact. The values for nss, which were extracted in the manner of Hill-Coleman, were 1.23×1011 eV-1 cm-2 at 2 MHz and 6.51×1012 eV-1 cm-2 at 20 kHz. This result was an indicator of the occurrence of interface states at the zone of the junction interface performing as a source of leakage current and a trap center for the carriers originated by light.

3.
Chemosphere ; 238: 124700, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524602

RESUMO

An eight-year field trial was conducted to investigate the effects of four different N fertilization treatments of urea (CO(NH2)2, the control), ammonium sulfate ((NH4)2SO4), ammonium chloride (NH4Cl), and ammonium hydrogen phosphate [(NH4)2HPO4]) on cadmium (Cd) phytotoxicity in rice and soil microbial communities in a Cd-contaminated paddy of southern China. The results demonstrate that the different N treatments exerted different effects: the application of (NH4)2HPO4 and (NH4)2SO4 significantly increased rice grain yield and decreased soil-extractable Cd content when compared with those of the control, while NH4Cl had a converse effect. Expression of genes related to Cd uptake (IRT and NRAPM genes) and transport (HMA genes) by roots may be responsible for Cd phytotoxicity in rice grown in the different N fertilization treatments. Our results further demonstrate that N fertilization had stronger effects on soil bacterial communities than fungal communities. The bacterial and fungal keystone species were identified by phylogenetic molecular ecological network (pMEN) analysis and mainly fell into the categories of Gammaproteobacteria, Acidobacteria and Actinobacteria for the bacterial species and Ascomycota for the fungal species; all of these keystone species were highly enriched in the (NH4)2HPO4 treatment. Soil pH and soil available-Cd content emerged as the major determinants of microbial network connectors. These results could provide effective fertilizing strategies for alleviating Cd phytotoxicity in rice and enhance the understanding of its underlying microbial mechanisms.

4.
J Biomed Mater Res A ; 108(1): 148-156, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31515902

RESUMO

In order to improve the treatment efficacy and reduce the side effects, the synergistic therapy has been effectively exploited in cancer treatment. Herein, we fabricated a kind of acid-sensitive ROS-triggered dextran-based drug delivery system (DHTD/Zn-TPP) for synergistic therapy, in which chemotherapeutics doxorubicin was conjugated to the dextran backbone via ROS cleavable thioketal conjugates while photosensitizer porphyrin (Zn-TPP) was encapsulated via acid-responsive metallic coordinated interaction. The structure and acid-responsive self-assemble behavior of DHTD/Zn-TPP were measured by 1 H NMR, Fourier transform infrared, dynamic laser scattering, and transmission electron microscopy. Further, the in vivo ROS-triggered DOX release and anticancer efficiency were evaluated toward HeLa cells and MCF-7 cells. All the data obtained verified that DHTD/Zn-TPP had a significantly improved cell growth inhibitory effect with light irritation due to the combined application of photodynamic-chemotherapy.

5.
Water Res ; 168: 115164, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629229

RESUMO

Carbamazepine (CBZ) is a typical pharmaceutical residue commonly found in aqueous environments, but its removal through activated carbon or advanced oxidation processes is often disrupted by co-existing organic matter. An imprinting system which consisted of the target pollutant CBZ (template molecule) and 10 different kinds of functional monomers was constructed via molecular simulation to screen for appropriate monomers, thereby addressing CBZ removal disruptions. An annealing method simulation was used to search for stable, low-energy conformations of the template-monomer interaction system to calculate the binding energy of these different monomers with CBZ. The order of binding affinity calculated was: 4-vinylbenzoic acid > itaconic acid > methacrylic acid, which was consistent with the experimental observations. The adsorption capacity of the molecular imprinted polymer (MIP) prepared using 4-vinylbenzoic acid reached 28.40 mg/g, and the imprinting factor reached 2.72. The simulation and measurement of the ultraviolet spectrum of the imprinting system showed that a new interaction system was formed between the template and monomers, and that multiple binding conformations between them took place when specific recognition occurred. Energy calculation and hydrogen bond analysis revealed that the van der Waals force, including the π-π conjugate and electrostatic forces including hydrogen bonding, played an important role during selective adsorption, which was confirmed by infrared spectroscopy analysis.


Assuntos
Poluentes Ambientais , Impressão Molecular , Preparações Farmacêuticas , Adsorção , Carbamazepina
6.
Ultrasound Med Biol ; 46(1): 180-187, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31582179

RESUMO

This article aims to test a minimally invasive interventional approach by real-time transcranial contrast-enhanced ultrasound (CEUS) through a small bur hole to achieve an early local hemostatic drug therapy in a novel traumatic intracerebral hematoma (ICH) model of pigs with hemostatic abnormalities. The effects of hemostasis in the hemocoagulase atrox (HA) injection group and saline injection group groups were observed by transcranial CEUS at three time points: 0 s, 10 s, 2nd. We successfully established a novel traumatic ICH model of pigs with hemostatic abnormalities by the methods of interventional ultrasound techniques and observed the effect of hemostasis by using HA in a local injection method with the assistance of minimally invasive interventional ultrasound technique. At 0 s, four pigs (100%) were observed that active bleeding was significantly weakened, and the range of hematoma became smaller in the HA group. At 10 s, four pigs (100%) were observed that active bleeding became much weaker, and the range of hematoma became further smaller in the HA group. At 2nd, zero pigs (0/4, 0%) were observed that active bleeding could be clearly identified and four pigs (100%) with ICH could also be observed in the HA group. We believe this useful technique could minimize the invasiveness and be operated at the bedside, which would bring much more benefits for traumatic ICH patients.

7.
Nurse Educ Today ; 84: 104205, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734641

RESUMO

BACKGROUND: Smoking is common among nursing students worldwide, but the reported prevalence is inconsistent across epidemiological studies. This is a meta-analysis of the prevalence of smoking in nursing students worldwide. DESIGN: Meta-analysis of observational studies. SAMPLE: A total of 46 studies were included in this meta-analysis. METHOD: Electronic databases (PubMed, Medline, PsycINFO, EMBASE and Web of science) were independently and systematically searched by two investigators from their commencement date up to 12 May 2018. Studies that reported the smoking rate of nursing students were included and analyzed using random-effects model. RESULTS: The pooled prevalence of current smoking was 26.6% (95% CI: 22.9-30.4%), while pooled prevalence of previous smoking was 15.5% (95% CI: 11.8-19.3%). Subgroup analyses showed that smoking rate was higher in male compared with female students (39% vs 25.2%, P < .001), while survey time, sample size, age, study design and academic year did not moderate the smoking rate (all P > .05). CONCLUSION: This meta-analysis confirmed that smoking is common in nursing students. Considering the negative impact of smoking on health, appropriate smoking cessation measures for nursing students should be developed.

8.
Behav Sleep Med ; : 1-14, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672062

RESUMO

Objective: Poor sleep quality is common in nursing staff. This meta-analysis aimed to examine the pooled prevalence of poor sleep quality in nursing staff.Methods: A systematic search in PubMed, EMBASE, PsycINFO, and Web of Science databases was performed. Studies that reported sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) were synthesized using a random-effects model.Results: Fifty-three studies were analyzed. The pooled prevalence of poor sleep quality was 61.0% (95% CI: 55.8-66.1%). The pooled total PSQI score was 7.13 ± 0.18 (95% CI: 6.78-7.50). The pooled component scores were 1.47 ± 0.20 (95% CI of mean score: 1.08-1.85) in sleep latency, 0.91 ± 0.15 (95% CI of mean score: 0.61-1.21) in sleep duration, 1.59 ± 0.13 (95% CI of mean score: 1.35-1.84) in overall sleep disturbances, 0.33 ± 0.18 (95% CI of mean score: 0-0.67) in sleeping medication, 1.21 ± 1.20 (95% CI of mean score: 0.83-1.60) in daytime dysfunction, 1.39 ± 0.14 (95% CI of mean score: 1.11-1.67) in subjective sleep quality, and 0.66 ± 0.11 (95% CI of mean score: 0.44-0.87) in habitual sleep efficiency. Subgroup and meta-regression analyses found that PSQI cutoff values, mean age, body mass index (BMI), sample size, study quality, and work experience moderated the prevalence of poor sleep quality.Conclusions: Poor sleep quality appears to be common in nursing staff. Considering its negative impact on health, effective measures should be taken to improve poor sleep quality in this population. Longitudinal studies should be conducted to examine the contributing factors of nurses' poor sleep quality.

9.
Opt Express ; 27(21): 29676-29684, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684225

RESUMO

Laser wakefield accelerators have emerged as a promising candidate for compact synchrotron radiation and even x-ray free electron lasers. Today, to make the electrons emit electromagnetic radiation, the trajectories of laser wakefield accelerated electrons are deflected by transverse wakefield, counter-propagating laser field or external permanent magnet insertion device. Here, we propose a novel type of undulator that has a period of a few hundred microns and a magnetic field of tens of Tesla. The undulator consists of a bifilar capacitor-coil target that sustains a strong discharge current that generates a helical magnetic field around the coil axis when irradiated by a high-energy laser. Coupling this undulator with state-of-the-art laser wakefield accelerators can, simultaneously, produce ultra-bright quasi-monochromatic x-rays with tunable energy ranging 5-250 keV and optimize the free electron laser parameter and gain length compared with a permanent magnet-based undulator. This concept may pave a path toward ultra-compact synchrotron radiation and even x-ray free electron lasers.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31685428

RESUMO

A sensitive and selective nanoprobe for detection of hypochlorite (OCl-) based on 4-aminoantipyrine (AAP) modified carbon dots (CDs-AAP) has been prepared. The CDs-AAP exhibit an emission peak at 484 nm when the excitation wavelength is 370 nm, accompanying 36 nm red shift compare with the pristine CDs. The addition of OCl- lead to the AAP on the surface of CDs experience a process of hydrazide hydrolysis and double bond addition, causing the singlet and triplet electrons of the excited state more closer in energy (ie, the energy difference between the two is reduced), eventually quenching the fluorescence of CDs due to heavy atomic effects. Central composite design (CCD) and response surface method (RSM) were used to optimize the detection variables of pH, incubation time and temperature. The designed model study indicated that the optimum detection conditions was pH 7.0, temperature 30 °C and incubation time 20 min, respectively. Under optimal conditions, the fluorescent intensity of the nanoprobe linearly responded to the OCl- concentration from 3 µM to 36 µM and the limit of detection was 40 nM. The proposed nanoprobe was successfully used to the detection of OCl- in tap water and pool water, and the recovery were in the range of 94% - 103%. In addition, the nanoprobe was also applied in imaging of VMSCs cells and labeling E.coli.

11.
Chemosphere ; 242: 125112, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31669993

RESUMO

This investigation was made to examine the role of indole-3-acetic acid (IAA), gibberellin A3 (GA3), 6-Benzylaminopurine (6-BA), and 24-epibrassinolide (EBL) in improving stress tolerance and phytoremediation of the cadmium (Cd) and uranium (U) by mustard (Brassica juncea L.). The optimum concentrations of IAA, GA3, 6-BA, and EBL were determined based on plant biomass production, metal uptake, translocation, and removal efficiency. The biomass and total chlorophyll content decreased under Cd and U stress. Nevertheless, the application of IAA, GA3, and 6-BA significantly (p < 0.05) increased the growth and total chlorophyll content of mustard. The malondialdehyde (MDA) and H2O2 content of mustard were enhanced under Cd and U stress, but they were significantly (p < 0.05) decreased in plant growth regulators (PGRs) treatments (except for EBL). PGRs treatments increased activities of antioxidant enzymes such as superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase, thus reducing the oxidative stress. Furthermore, the shoot uptake of Cd and U of IAA and EBL treatments was significantly (p < 0.05) higher than that of other treatments. IAA and EBL also have more significant effects on the translocation and remediation of Cd and U compared to GA3 and 6-BA. The removal efficiency of Cd and U reached the maximum in the 500 mg L-1 IAA treatment, which was 330.77% and 118.61% greater than that in the control (CK), respectively. These results suggested that PGRs could improve the stress tolerance and efficiency of phytoremediation using B. juncea in Cd- and U- contaminated soils.

12.
BMC Psychiatry ; 19(1): 344, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694611

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is the most rapid and effective treatment for patients with depression, ECT can achieve remarkable antidepressant effects in the initial 3-4 sessions, but significant side effects limit its use. However, recent low-charge electrotherapy (LCE) studies have demonstrated antidepressant or antipsychotic effects with significantly fewer side effects. The aim of this study is to propose a novel two-step charge set strategy for ECT treatment, referred to as Hybrid-ECT, to decrease side effects by using a low charge while preserving treatment efficacy. METHODS/DESIGN: A randomized, double-blinded, standard-controlled, parallel-group design will be carried out. We plan to enroll 112 inpatients diagnosed with depression (unipolar or bipolar) and randomly assign them to conventional ECT (control group) or to Hybrid-ECT (treatment group, 3 ECT sessions followed by LCE sessions (approximately 2.8 joules per session)). We will evaluate participants across a wide variety of domains including clinical symptoms, cognitive, psychological and functional metrics. We will also perform magnetic resonance imaging (MRI) and event-related potential (ERPs) assessments during treatment to explore brain function differences between ECT and LCE. DISCUSSION: This research proposes a simple but completely novel ECT strategy that aims to rapidly relieve depressive symptoms and minimize side effects. The mechanism of ECT and LCE will be further discussed. TRIAL REGISTRATION: Chinese Clinical Trial Registry, Number: ChiCTR1900022905 (Registration date: April 30, 2019).

13.
J Med Chem ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721578

RESUMO

Gastrointestinal stromal tumors (GISTs) are prototypes of stem cell factor receptor (c-KIT)-driven cancer. Two receptor tyrosine kinases, c-KIT and fms-tyrosine kinase (FLT3), are frequently mutated in AML patients, and these mutations are associated with poor prognosis. In this study, we discovered a multitargeted tyrosine kinase inhibitor, compound 15a, with potent inhibition against single or double mutations of c-KIT developed in GISTs. Moreover, crystal structure analysis revealed the unique binding mode of 15a with c-KIT and may elucidate its high potency in inhibiting c-KIT kinase activity. Compound 15a inhibited cell proliferation and induced apoptosis by targeting c-KIT in c-KIT-mutant GIST cell lines. The antitumor effects of 15a were also demonstrated in GIST430 and GIST patient-derived xenograft (PDX) models. Further studies demonstrated that 15a inhibited the proliferation of c-KIT- and FLT3-driven AML cells in vitro and in vivo. The results of this study suggest that 15a may be a potential anticancer drug for the treatment of GISTs and AML.

14.
J Ultrasound Med ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724216

RESUMO

OBJECTIVES: To determine whether real-time 3-dimensional ultrasound (RT3DUS) could provide additional information on early detection and evaluation in the management of solid abdominal organ trauma based on an animal model. METHODS: Nine bleeding lesions were developed in the livers (n = 3), kidneys (n = 3), and spleens (n = 3) from 9 pigs. An ultrasound contrast agent was administered intravenously (liver, 0.025 mL/kg; kidney, 0.008 mL/kg; and spleen, 0.013 mL/kg) after an unenhanced 2-dimensional ultrasound (2DUS) examination (B-mode and color Doppler). After contrast agent injection, bleeding lesions were imaged by 2DUS and sequentially imaged by 3-dimensional static ultrasound (3DSUS) and RT3DUS to identify active bleeding, observe the relationship between bleeding lesions and peripheral blood vessels, and evaluate the spatial scope of the bleeding lesions in the organs. RESULTS: For the identification of active bleeding, there was no statistical difference in contrast-enhanced 2DUS, 3DSUS, and RT3DUS. For observation of the relationship between bleeding lesions and peripheral blood vessels, RT3DUS performed statistically better than 2DUS (P < .05), as reconstructed RT3DUS could show more information about the relationship. For the evaluation of the spatial scope of the bleeding lesion in the organ, RT3DUS also performed statistically better than 2DUS from the multiplanar observation by postprocessing of the 3-dimensional real-time volumes (P < .05). CONCLUSIONS: Real-time 3-dimensional ultrasound improves early detection and evaluation of solid abdominal organ trauma and provides additional information over the current contrast-enhanced 2DUS.

15.
Langmuir ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724868

RESUMO

Wicking of wetting liquids into micro-patterns of posts with homogeneous triangular cross-section is studied in experiments and by numerical energy minimizations. To test for directional wicking we fabricated regular arrays of posts with various combinations of line fractions and aspect ratios using standard photolithography processes. In agreement with numerical energy minimizations of the liquid film morphology, we find spontaneous wicking in the experiments only for line fractions and aspect ratios where the homogeneous liquid film represents the state of lowest interfacial free energy and where no local energy minimum could be detected in our numerical energy minimizations. The numerical results further demonstrate that the stability of a certain morphology of the terminal meniscus controls the direction of wicking relative to the orientation of the triangular posts. The observed selectivity of spontaneous wicking in respect to the meniscus orientation can be exploited to build a micro-fluidic rectifier for partially wetting liquids.

16.
Chemistry ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696989

RESUMO

The anion binding and transport properties of an extensive library of thiophene-based molecules are reported. Seventeen bis-urea positional isomers, with different binding conformations and lipophilicities, were synthetized by the appendage of α-, ß-thiophene or α-, ß-, γ-benzo[ b ]thiophene motifs to the ortho -phenylenediamine central core, yielding six subsets of positional isomers. Through 1 H NMR, X-ray crystallography, molecular modelling and anion efflux studies, it was demonstrated that most active transporters display a pre-organised binding conformation able to promote the recognition of chloride using urea and C-H binding groups in a cooperative fashion. Additional LUV based assays, carried out under electroneutral and electrogenic conditions, together with NMDG-Cl assays, indicate that anion efflux occurs mainly through H + /Cl - symport mechanism. On the other hand, the most efficient anion transporter displays cytotoxicity against tumour cell lines while having no effects on a cystic fibrosis cell line.

17.
Nutrients ; 11(11)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31689947

RESUMO

Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy. However, there is still no consensus on the effects of isoflavones despite over two decades of vigorous research. This systematic review aims to summarize the current literature on isoflavone supplements, focusing on the active ingredients daidzein, genistein, and S-equol, and provide a framework to guide future research. We performed a literature search in Ovid Medline using the search terms "isoflavone" and "menopause", which yielded 95 abstracts and 68 full-text articles. We found that isoflavones reduce hot flashes even accounting for placebo effect, attenuate lumbar spine bone mineral density (BMD) loss, show beneficial effects on systolic blood pressure during early menopause, and improve glycemic control in vitro. There are currently no conclusive benefits of isoflavones on urogenital symptoms and cognition. Due to the lack of standardized research protocols including isoflavone component and dosage, outcomes, and trial duration, it is difficult to reach a conclusion at this point in time. Despite these limitations, the evidence thus far favors the use of isoflavones due to their safety profile and benefit to overall health.

18.
Cereb Cortex ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690946

RESUMO

The striatopallidal pathway is specialized for control of motor and motivational behaviors, but its causal role in striatal control of instrumental learning remains undefined (partly due to the confounding motor effects). Here, we leveraged the transient and "time-locked" optogenetic manipulations with the reward delivery to minimize motor confounding effect, to better define the striatopallidal control of instrumental behaviors. Optogenetic (Arch) silencing of the striatopallidal pathway in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS) promoted goal-directed and habitual behaviors, respectively, without affecting acquisition of instrumental behaviors, indicating striatopallidal pathway suppression of instrumental behaviors under physiological condition. Conversely, striatopallidal pathway activation mainly affected the acquisition of instrumental behaviors with the acquisition suppression achieved by either optogenetic (ChR2) or chemicogenetic (hM3q) activation, by strong (10 mW, but not weak 1 mW) optogenetic activation, by the time-locked (but not random) optogenetic activation with the reward and by the DMS (but not DLS) striatopallidal pathway. Lastly, striatopallidal pathway modulated instrumental behaviors through striatopallidal output projections into the external globus pallidus (GPe) since optogenetic activation of the striatopallidal pathway in the DMS and of the striatopallidal output projections in the GPe similarly suppressed goal-directed behavior. Thus, the striatopallidal pathway confers distinctive and inhibitory controls of animal's sensitivity to goal-directed valuation and acquisition of instrumental behaviors under normal and over-activation conditions, through the output projections into GPe.

19.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692057

RESUMO

Renal tubular epithelial cells may undergo epithelial-mesenchymal transition (EMT) in response to stimuli, such as transforming growth factor (TGF)-ß1, leading to myofibroblast activation and renal fibrosis. The formin mDia1 is required for nucleation and polymerization of actin and the microtubule cytoskeleton. The present study sought to explore the role of mDia1 in EMT of tubular epithelial cells. A rat model of unilateral ureteral obstruction (UUO) was established. The expression of TGF-ß1, collagen I, collagen III, and mDia1 in the kidneys was examined at day 7 after surgery. The effect of mDia1 on EMT was explored in NRK-52E cells by exposing them to TGF-ß1. Increased expression of TGF-ß1, collagen I, collagen III, and mDia1 was found in obstructive kidneys of UUO model rats. Exposing rat tubular epithelial cells to TGF-ß1 promoted collagen I and collagen III expression but had no effect on mDia1 expression. Silencing mDia1 expression impeded epithelial cell migration as well as reduced TGF-ß1, collagen, and Profilin1 expression, whereas mDia1 overexpression exerted an opposite effect. Furthermore, mDia1 regulated the expression of vimentin, α-smooth muscle actin, and E-cadherin and focal adhesion-kinase (FAK)/Src activation through Profilin1. Inhibition of the mDia1 activator RhoA by fasudil reversed EMT, and FAK/Src activation induced by mDia1. In conclusion, mDia1 regulated tubular epithelial cell migration, collagen expression, and EMT in NRK-52E cells exposed to TGF-ß1. Thus, suppression of mDia1 activation might be a strategy to counteract renal fibrosis.

20.
Curr Pharm Des ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692421

RESUMO

BACKGROUND: The current study was to examine the specific activation of pro-inflammatory cytokines (PICs), namely IL-1ß, IL-6 and TNF-α in the cochlear spiral ganglion of rats after ototoxicity induced by cisplatin. Since γ-aminobutyric acid (GABA) and its receptors are involved in pathophysiological processes of ototoxicity, we further examined the role played by PICs in regulating expression of GABA transporter type 1 and 3 (GAT-1 and GAT-3), as two essential subtypes of GATs responsible for the regulation of extracellular GABA levels in the neuronal tissues. METHODS: ELISA and western blot analysis were employed to examine the levels of PICs and GATs; and auditory brainstem response was used to assess ototoxicity induced by cisplatin. RESULTS: IL-1ß, IL-6 and TNF-α as well as their receptors were significantly increased in the spiral ganglion of ototoxic rats as compared with sham control animals (P<0.05, ototoxic rats vs. control rats). Cisplatin-ototoxicity also induced upregulation of the protein levels of GAT-1 and GAT-3 in the spiral ganglion (P<0.05 vs. controls). In addition, administration of inhibitors to IL-1ß, IL-6 and TNF-α attenuated amplification of GAT-1 and GAT-3 and improved hearing impairment induced by cisplatin. CONCLUSION: our data indicate that PIC signals are activated in the spiral ganglion during cisplatin-ototoxicity which thereby leads to upregulation of GABA transporters. As a result, it is likely that de-inhibition of GABA system is enhanced in the cochlear spiral ganglion. This support a role for PICs in engagement of the signal mechanisms associated with cisplatin-ototoxicity, and has pharmacological implications to target specific PICs for GABAergic dysfunction and vulnerability related to cisplatin-ototoxicity.

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