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1.
J Hazard Mater ; 393: 122325, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32126422

RESUMO

SnS2 nanosheets (NSs) have become an ideal candidate for high performance gas sensors due to their unique sensing properties. However, the restacking and aggregation in the process of sensor manufacturing have great influence on the gas sensing performance. In this study, we synthesized a novel heterojunction of the flower-like porous SnS2 NSs with edge exposed MoS2 nanospheres via a facile hydrothermal method and sensitive response has achieved at room temperature (27℃). After functionalization, the SMS-Ⅱ showed excellent response (Ra/Rg = 25.9-100 ppm NO2), which is 22.3 times higher than that of the pristine SnS2 NSs. The sensor also has the characteristics of short response time of 2 s, excellent base line recovery (28.2 s), long-term stability and reliability within 16 weeks, good selectivity and low detection concentration of only 50 ppb. The p-n heterojunction formed between the edge-exposed spherical MoS2 and the 3D flower-like SnS2 NSs has a synergistic effect, providing a highly active sites for the adsorption of NO2 gas, which greatly enhance the sensitivity of the sensor. Simple fabrication and excellent gas sensing performance of the SnS2/MoS2 heterostructure nanomaterials (NMs) will highly effective for commercial gas sensing application.

2.
Mol Ther Nucleic Acids ; 20: 292-307, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32199127

RESUMO

Recently, the identification of several circular RNAs (circRNAs) as vital regulators of microRNAs (miRNAs) underlines the increasing complexity of non-coding RNA (ncRNA)-mediated regulatory networks. This study aimed to explore the effects of mmu_circ_0000790 on the biological behaviors of pulmonary artery smooth muscle cells (PASMCs) in hypoxic pulmonary hypertension (HPH). The HPH mouse model and hypoxia-induced PASMC model were initially established, and the expression of mmu_circ_0000790 in the pulmonary vascular tissues and hypoxic PASMCs was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). A series of in vitro experiments such as dual-luciferase, RNA pull-down, and RNA-binding protein immunoprecipitation (RIP) assays were conducted to evaluate the interactions among mmu_circ_0000790, microRNA-374c (miR-374c), and forkhead transcription factor 1 (FOXC1). The potential physiological functions of mmu_circ_0000790, miR-374c, and FOXC1 in hypoxic PASMCs were investigated through gain- and loss-of function approaches. Upregulated mmu_circ_0000790 was found in both the HPH-pulmonary vascular tissues and hypoxic PASMCs. Additionally, mmu_circ_0000790 could competitively bind to miR-374c and consequently upregulate the target gene of miR-374c, FOXC1. It was also observed that mmu_circ_0000790 induced proliferation and inhibited apoptosis of hypoxic PASMCs, which further promoted the pulmonary vascular remodeling in mice with HPH. Therefore, we speculate that mmu_circ_0000790 may serve as a prospective target for the treatment of patients with HPH.

3.
Int J Biol Macromol ; 151: 855-860, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32068062

RESUMO

The aim of this study was to evaluate the spatial structure and potential antifatigue activity of polysaccharide fractions which was extracted from Inonotus obliquus. The first polysaccharide fractions of Inonotus obliquus (PIO-1) were obtained after hot-water extraction and purification by DEAE cellulose-52 chromatography. Results of the forced swimming test showed that the doses (50 mg/kg) of PIO-1 could increase the climbing duration and swimming time as well as reduced the immobility time in the PIO treated mice. The fatigue related metabolic parameters showed that PIO-1 decreased the level of blood lactic acid (BLA), urea nitrogen (BUN) and lactic dehydrogenase (LDH). Additionally, PIO-1 significantly decreased the 5-HT concentrations in the mice brain. The results of monosaccharide analysis showed that the molar ratio of mannose, glucose, galactose, xylose and arabinose with the molar ratio of 1.0:1.9:3.5:18.5:5.7. The molecular morphology of the PIO-1 observed under atomic force microscopy (AFM). There were many spherical and heterogeneous clumps existed in the images. Therefore, current study indicated polysaccharide PIO-1 not only has great potential to postpone physical fatigue but also shown potential to improve mental fatigue.

4.
Bioinformatics ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904817

RESUMO

MOTIVATION: Polyadenylation plays a regulatory role in transcription. The recognition of polyadenylation signal (PAS) motif sequence is an important step in polyadenylation. In the past few years, some statistical machine learning-based and deep learning-based methods have been proposed for PAS identification. Although these methods predict PAS with success, there is room for their improvement on PAS identification. RESULTS: In this study, we proposed a deep neural network-based computational method, called SANPolyA, for identifying PAS in human and mouse genomes. SANPolyA requires no manually crafted sequence features. We compared our method SANPolyA with several previous PAS identification methods on several PAS benchmark datasets. Our results showed that SANPolyA outperforms the state-of-art methods. SANPolyA also showed good performance on leave-one-motif-out evaluation. AVAILABILITY: https://github.com/yuht4/SANPolyA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

5.
FASEB J ; 34(1): 1018-1037, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914603

RESUMO

Recombinant antimicrobial peptide microcin J25 (MccJ25) causes potent antimicrobial activity against enterotoxigenic Escherichia coli (ETEC) in vitro; however, independently of this activity, its role in suppressing intestinal inflammation and epithelial barrier injury in vivo remains unclear. We investigated the therapeutic effects of MccJ25 on intestinal inflammation and epithelial barrier dysfunction and the underlying mechanism, using gentamicin for comparison. In a mouse model of intestinal inflammation, therapeutic administration of either MccJ25 or gentamicin after ETEC K88 infection attenuated clinical symptoms, reduced intestinal pathogen colonization, improved intestinal morphology, and decreased inflammatory pathologies and intestinal permeability, ultimately improving the hosts' health. MccJ25 also attenuated ETEC-induced mouse intestinal barrier dysfunction by enhancing tight junction proteins (TJPs). Using the human epithelial cell line Caco-2, we verified the epithelial barrier-strengthening and mucosal injury-alleviating effects of MccJ25 on ETEC infection: increased expression of TJPs by activating the p38/MAPK pathway, balancing the microbiota, and improving short-chain fatty acid concentrations in the cecum of ETEC-infected mice. Although gentamicin and MccJ25 had similar effects in the inflamed gut, MccJ25 was superior to gentamicin with regard to defending the host from ETEC infection. Overall, MccJ25 may be a promising therapeutic drug for treating enteric pathogen-induced intestinal inflammation diseases.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31967775

RESUMO

High-performance HCHO sensors are of great importance in various application fields such as indoor air quality assessments. Herein, bimetallic Ag-Pt nanoparticles are synthesized as high-performance catalysts for ZnO-based gas sensors. Spherical aberration (Cs)-corrected transmission electron microscopy images with atomic resolution clearly indicate that the prepared nanoparticles exhibit a novel Ag@Pt core-shell nanostructure with a pentagram shape. For high-performance HCHO sensor construction, integrated micro-electrodes are first fabricated with the microelectromechanical system (MEMS) technology. Then, the hydrothermal route is used to self-assemble well-aligned ZnO nanowire arrays onto the sensing microregion. After that, the pentagram-shaped Ag@Pt nanoparticles are loaded onto the surface of ZnO nanowires with the inkjet printing technique to form MEMS sensors with Ag@Pt@ZnO as the sensing material. The thoroughly sensing experiments indicate that the Ag@Pt nanoparticles exhibit satisfied catalytic activation to HCHO molecules. The experimental observed detection limit of our sensor to HCHO reaches the parts per billion level. To elucidate the HCHO-sensing mechanism, the online mass spectrum (online MS) is utilized to analyze the components of exhaust gas stream of HCHO flowing through the Ag@Pt@ZnO material. The online MS indicates that with the Ag@Pt catalyst, HCHO molecules are partially oxidized to HCOOH molecules at low temperatures and are completely oxidized to CO2 molecules at high temperatures.

7.
Future Microbiol ; 15: 49-61, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31920092

RESUMO

Aim: To compare the genome sequences among clinical and American-Type Culture Collection Ureaplasma strains and to reveal the potential molecular mechanisms of multiple banded antigen (MBA) variation. Materials & methods: Two strains of Ureaplasma urealyticum 132 and 315 and one strain of Ureaplasma parvum 106 isolated from infertile males were sequenced using Illumina and Nanopore technologies. Comparative genomic analysis was performed of the three strains and two American-Type Culture Collection strains. Results & conclusion: The Ureaplasma species shared a core genome. Strains 132 and 315 shared a distant relationship with previously sequenced Ureaplasma spp. The MBA locus is more informative for studying MBA mutations than is the mba gene alone. The mechanisms of MBA variation are more flexible and complex than previously reported. The variation in MBA is not limited to the mba gene but occurs in other genes within the MBA locus.

8.
Int J Neural Syst ; 30(1): 1950017, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31390911

RESUMO

We employed high-density microelectrode arrays to investigate spontaneous firing patterns of neurons in brain circuits of the primary somatosensory cortex (S1) in mice. We recorded from over 150 neurons for 10min in each of eight different experiments, identified their location in S1, sorted their action potentials (spikes), and computed their power spectra and inter-spike interval (ISI) statistics. Of all persistently active neurons, 92% fired with a single dominant frequency - regularly firing neurons (RNs) - from 1 to 8Hz while 8% fired in burst with two dominant frequencies - bursting neurons (BNs) - corresponding to the inter-burst (2-6Hz) and intra-burst intervals (20-160Hz). RNs were predominantly located in layers 2/3 and 5/6 while BNs localized to layers 4 and 5. Across neurons, the standard deviation of ISI was a power law of its mean, a property known as fluctuation scaling, with a power law exponent of 1 for RNs and 1.25 for BNs. The power law implies that firing and bursting patterns are scale invariant: the firing pattern of a given RN or BN resembles that of another RN or BN, respectively, after a time contraction or dilation. An explanation for this scale invariance is discussed in the context of previous computational studies as well as its potential role in information processing.

9.
Environ Int ; 134: 105296, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759273

RESUMO

BACKGROUND: There is a paucity of mechanistic information on the DNA methylation and particulate matter (PM) exposure. This study aimed to investigate the association of PM and its component with DNA methylation, and the roles of DNA methyltransferase (DNMTs). METHODS: There were 240 high-exposed, 318 low-exposed and 210 non-exposed participants in this study. Individual concentrations of PM, polycyclic aromatic hydrocarbons (PAHs) and metals were identified by the monitoring data in their workplaces. Urinary 1-OHP and metals were determined as exposure markers. The global DNA methylation (% 5mC) and the mRNA expression of DNMT1, DNMT3A and DNMT3B were measured. We used mediation analysis to evaluate the role of DNMTs expression on DNA methylation alteration induced by PAHs and metals components. RESULTS: The decreasing trend of % 5mC was associated with increment of PM exposure in all subjects. We found that one IQR increase in total PAHs (3.82 µg/m3) and urinary 1-OHP (1.06 µmol/mol creatinine) were associated with a separate 6.08% and 7.26% decrease in % 5mC (P = 0.009, P < 0.001), and one IQR increase in urinary Ni (27.75 µmol/mol creatinine) was associated with a 3.29% decrease in % 5mC (P = 0.03). The interaction of urinary 1-OHP with Ni on global DNA methylation (%5mC) was not found (P interaction = 0.89). PM exposure was significantly associated with decreased mRNA level of DNMT3B, but the mediated effect of the PAHs and Ni levels on % 5mC through the DNMT3B pathway was not observed. CONCLUSIONS: We found the decrement of global DNA methylation and DNMT3B expression with elevated PM levels in population. The independent mode of action on DNA hypomethylation was found from PAHs and metal components. Global DNA hypomethylation might be a potential biomarker for evaluation of adverse health effects in response to PM exposure.

10.
Sleep Breath ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31832981

RESUMO

PURPOSE: To study and analyze the sleep quality and sleep structure of patients with vestibular migraine (VM). METHODS: In this cross-sectional case-control study, the Pittsburgh Sleep Quality Index (PSQI) questionnaire and polysomnography (PSG) were used to compare the clinical characteristics of sleep disorders in 49 patients with VM, 52 patients with migraine, and 54 controls. RESULTS: The VM, migraine, and control groups did not significantly differ in terms of age or sex. Compared with the migraine and control groups, the VM group had a higher incidence of poor sleep quality (χ2 = 36.618, p < 0.01) and greater severity of poor sleep quality (p < 0.01). Furthermore, the VM group showed reduced sleep efficiency (p < 0.01) and reduced proportions of REM and slow wave (N3) sleep (p ≤ 0.01). Conversely, sleep latency (p = 0.01) and REM latency (p = 0.04) were prolonged, and proportions of light sleep phases (N1, p < 0.05, and N2, p < 0.01) and the micro-arousal index (p = 0.03) were increased. The migraine group had significantly higher apnea hypopnea (AHI) and periodic leg movement (PLMI) indices than the VM group. CONCLUSION: We report an effect of VM on sleep structure and an association with migraine. Similar to migraine, VM affects the sleep regulation centers and causes structural sleep disorders.

11.
BMC Biol ; 17(1): 106, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852478

RESUMO

BACKGROUND: The early-life microbiota exerts a profound and lifelong impact on host health. Longitudinal studies in humans have been informative but are mostly based on the analysis of fecal samples and cannot shed direct light on the early development of mucosa-associated intestinal microbiota and its impact on GI function. Using piglets as a model for human infants, we assess here the succession of mucosa-associated microbiota across the intestinal tract in the first 35 days after birth. RESULTS: Although sharing a similar composition and predicted functional profile at birth, the mucosa-associated microbiome in the small intestine (jejunum and ileum) remained relatively stable, while that of the large intestine (cecum and colon) quickly expanded and diversified by day 35. Among detected microbial sources (milk, vagina, areolar skin, and feces of sows, farrowing crate, and incubator), maternal milk microbes were primarily responsible for the colonization of the small intestine, contributing approximately 90% bacteria throughout the first 35 days of the neonatal life. Although maternal milk microbes contributed greater than 90% bacteria to the large intestinal microbiota of neonates upon birth, their presence gradually diminished, and they were replaced by maternal fecal microbes by day 35. We found strong correlations between the relative abundance of specific mucosa-associated microbes, particularly those vertically transmitted from the mother, and the expression levels of multiple intestinal immune and barrier function genes in different segments of the intestinal tract. CONCLUSION: We revealed spatially specific trajectories of microbial colonization of the intestinal mucosa in the small and large intestines, which can be primarily attributed to the colonization by vertically transmitted maternal milk and intestinal microbes. Additionally, these maternal microbes may be involved in the establishment of intestinal immune and barrier functions in neonates. Our findings strengthen the notion that studying fecal samples alone is insufficient to fully understand the co-development of the intestinal microbiota and immune system and suggest the possibility of improving neonatal health through the manipulation of maternal microbiota.

12.
Sci Rep ; 9(1): 19806, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31875039

RESUMO

Methyl bromide (MB), a dominant ozone-depleting substance, is scheduled to be completely phased out for soil fumigation by December 30th 2018, in China. The combined effects of dimethyl disulfide (DMDS) plus metham sodium (MNa) were assessed in controlling soilborne pests for soil fumigation. A study was designed in laboratory for the evaluation of the efficacy of DMDS + MNa to control major soilborne pests. At the same time, two trials were conducted in cucumber field located in Tongzhou (in 2012) and Shunyi (in 2013), respectively, in order to assess the potential of DMDS + MNa in controlling soilborne pests. Laboratory studies disclosed positive synergistic effects of almost all four used combinations on Meloidogyne spp., Fusarium spp., Phytophthora spp., Abutilon theophrasti and Digitaria sanguinalis. Field trials found that DMDS + MNa (30 + 21 g a. i. m-2), both at a 50% reduced dose, effectively suppressed Meloidogyne spp. with a low root galling index (2.1% and 11.7%), significantly reduced the levels of Phytophthora and Fusarium spp. with a low root disease index (7.5% and 15.8%), gave very high cucumber yields (6.75 kg m-2 and 10.03 kg m-2), and increased income for cucumber growers with the highest economic benefits (20.91 ¥ m-2 and 23.58 ¥ m-2). The combination treatment provided similar results as MB standard dose treatment (40 g a. i. m-2) or DMDS standard dose treatment (60 g a. i. m-2) in pest control and yield, but was more effective than MNa standard dose treatment (42 g a. i. m-2). Usage of all chemical treatments gave better significant results than the untreated group of control. Considering the economic benefits, the DMDS plus MNa combination (30 + 21 g a. i. m-2) could be used for soil fumigation in cucumber production in China.

13.
Front Genet ; 10: 1071, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681441

RESUMO

DNA N6-methyladenine (6mA) is an important epigenetic modification, which is involved in many biology regulation processes. An accurate and reliable method for 6mA identification can help us gain a better insight into the regulatory mechanism of the modification. Although many experimental techniques have been proposed to identify 6mA sites genome-wide, these techniques are time consuming and laborious. Recently, several machine learning methods have been developed to identify 6mA sites genome-wide. However, there is room for the improvement on their performance for predicting 6mA sites in rice genome. In this paper, we developed a simple and lightweight deep learning model to identify DNA 6mA sites in rice genome. Our model needs no prior knowledge of 6mA or manually crafted sequence feature. We built our model based on two rice 6mA benchmark datasets. Our method got an average prediction accuracy of ∼93% and ∼92% on the two datasets we used. We compared our method with existing 6mA prediction tools. The comparison results show that our model outperforms the state-of-the-art methods.

14.
Clin Lab ; 65(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710433

RESUMO

BACKGROUND: A noninvasive, fast, highly sensitive and simple test is needed for cancer screening in addition to the detection of biomarkers in blood. Recently, the patent (CN102565055A) for the Urinary Monohydroxyphenyl Metabolites Assay (UMM-A) was authorized, and the effectiveness of clinical application has yet to be studied further. METHODS: A retrospective study was conducted consisting of 432 cancer patients, 28 benign tumor patients, 117 non-cancerous diseases patients, and 120 healthy donors to analyze the levels of monohydroxyphenyl metabolites in the urine sample. A logistic regression model was used to study the possible confounding factors affecting the diagnostic performance and to test the probability of a case to be positive for UMM-A. RESULTS: Compared with healthy donors, non-cancerous disease, and benign tumor subjects, the positive rate and MM level of UMM-A in cancer patients have significantly increased. After the 246 retreated cancer patients were excluded, and 186 untreated cancer patients were included, with the same specificity to 77.0%, the sensitivity improved from 66.7 to 89.8%, the negative predictive value improved from 58.6 to 91.4%. CONCLUSIONS: The present study has provided important information on the diagnostic characteristics of UMM-A for untreated cancer and its potential application in cancer screening.

15.
Int Immunopharmacol ; 77: 105922, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669891

RESUMO

PURPOSE: To explore potential biomarkers for identifying systemic lupus erythematosus (SLE) with liver injury. METHODS: This retrospective study examined the records of 158 SLE cases. The Apriori algorithm of association rules was employed to identify laboratory indexes related to liver injury in SLE patients. RESULTS: The ratio of albumin to globulin; levels of alpha-hydroxybutyrate dehydrogenase (α-HBDH), calcium, hemoglobin, urine protein, total cholesterol; absolute value of lymphocytes; red cell distribution width and hematocrit were identified by the Apriori algorithm from SLE-related liver injury patients. α-HBDH was identified as an independent risk factor for SLE-related liver injury. There were more SLE patients with liver injury in high-α-HBDH group than in low-α-HBDH group (64.63% vs. 21.05%; P < 0.001). In high-α-HBDH group, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (GGT), and the AST/ALT ratio were significantly higher, and albumin and complement 3 (C3) were markedly lower. Moreover, α-HBDH level was significantly higher in the SLE-related liver injury patients than in the non-SLE-related liver injury patients. In addition, α-HBDH was positively correlated with levels of AST and LDH, the AST/ALT ratio, and the SLE Disease Activity Index 2000, and it was negatively correlated with albumin and C3. The optimal cutoff value of α-HBDH for distinguishing SLE patients with and without liver injury was 258.50 U/L, which provided a 60.94% sensitivity and a 94.67% specificity. CONCLUSION: α-HBDH could be used to evaluate the disease activity of SLE-related liver injury, and it may be a potential biomarker for diagnosing SLE-related liver injury.

16.
Acta Pharmacol Sin ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31768045

RESUMO

Cadmium (Cd) is a nonessential heavy metal and a prevalent environmental toxin that has been shown to induce significant cardiomyocyte apoptosis in neonatal murine engineered cardiac tissues (ECTs). In contrast, zinc (Zn) is a potent metallothionein (MT) inducer, which plays an important role in protection against Cd toxicity. In this study, we investigated the protective effects of Zn against Cd toxicity in ECTs and explore the underlying mechanisms. ECTs were constructed from neonatal ventricular cells of wild-type (WT) mice and mice with global MT gene deletion (MT-KO). In WT-ECTs, Cd (5-20 µM) caused a dose-dependent toxicity that was detected within 8 h evidenced by suppressed beating, apoptosis, and LDH release; Zn (50-200 µM) dose-dependently induced MT expression in ECTs without causing ECT toxicity; co-treatment of ECT with Zn (50 µM) prevented Cd-induced toxicity. In MT-KO ECTs, Cd toxicity was enhanced; but unexpectedly, cotreatment with Zn provided partial protection against Cd toxicity. Furthermore, Cd, but not Zn, significantly activated Nrf2 and its downstream targets, including HO-1; inhibition of HO-1 by a specific HO-1 inhibitor, ZnPP (10 µM), significantly increased Cd-induced toxicity, but did not inhibit Zn protection against Cd injury, suggesting that Nrf2-mediated HO-1 activation was not required for Zn protective effect. Finally, the ability of Zn to reduce Cd uptake provided an additional MT-independent mechanism for reducing Cd toxicity. Thus, Zn exerts protective effects against Cd toxicity for murine ECTs that are partially MT-mediated. Further studies are required to translate these findings towards clinical trials.

17.
Life Sci ; 239: 117070, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751580

RESUMO

Doxorubicin (DOX) induced cardiotoxicity is a life-threatening side effect of chemotherapy and decreased cardiac function can present years after treatment. Despite the investigation of a broad range of pharmacologic interventions, to date the only drug shown to reduce DOX-related cardiotoxicity in preclinical studies and limited clinical trials is the iron chelating agent, dexrazoxane (DRZ), although the mechanisms responsible for DRZ mediated protection from DOX related cardiotoxicity remain unclear. Engineered cardiac tissues (ECTs) can be used for tissue repair strategies and as in vitro surrogate models to test cardiac toxicities and preventative countermeasures. Neonatal murine ECTs display cardiotoxicity in response to the environmental toxin, cadmium, and reduced cadmium toxicity with Zinc co-treatment, in part via the induction of the anti-oxidant Metallothionein (MT). We adapted our in vitro ECT model to determine the feasibility of using the ECT approach to investigate DOX-related cardiac injury and DRZ prevention. We found: (1) DOX induced dose and time dependent cell death in ECTs; (2) Zinc did not show protection from DOX cardiotoxicity; (3) MT overexpression induced by Zinc, low dose Cd pretreatment, or MT-overexpression (MT-TG) did not reduce ECT DOX cardiotoxicity; (4) DRZ reduced ECT DOX induced cell death; and (5) The mechanism of DRZ ECT protection from DOX cardiotoxicity was topoisomerase 2B (TOP2B) inhibition rather than reduced reactive oxygen species. Our data support the feasibility of ECTs as an in vitro platform technology for the investigation of drug induced cardiotoxicities including the role of TOP2B in DOX toxicity and DRZ mediated DOX toxicity prevention.


Assuntos
Cardiotoxicidade/metabolismo , Dexrazoxano/farmacologia , Miócitos Cardíacos/metabolismo , Animais , Animais Recém-Nascidos , Cardiotoxicidade/prevenção & controle , DNA Topoisomerases Tipo II/metabolismo , Dexrazoxano/metabolismo , Modelos Animais de Doenças , Doxorrubicina/toxicidade , Quelantes de Ferro/farmacologia , Metalotioneína/metabolismo , Camundongos , Camundongos Transgênicos , Miócitos Cardíacos/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Engenharia Tecidual/métodos
18.
Oxid Med Cell Longev ; 2019: 1479571, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781321

RESUMO

Age-related macular degeneration (AMD) represents a major reason for blindness in the elderly population. Oxidative stress is a predominant factor in the pathology of AMD. We previously evaluated the effects of phospholipid complex of quercetin (Q-PC) on oxidative injury in ARPE-19 cells, but the underlying mechanisms are not fully understood. Herein, the solid dispersion of quercetin-PC (Q-SD) was prepared with solubility being 235.54 µg/mL in water and 2.3×104 µg/mL in chloroform, which were significantly higher than that of quercetin (QT) and Q-PC. Q-SD also exhibited a considerably higher dissolution rate than QT and Q-PC. Additionally, Q-SD had Cmax of 4.143 µg/mL and AUC of 12.015 µg·h/mL in rats, suggesting better bioavailability than QT and Q-PC. Then, a mouse model of dry AMD (Nrf2 wild-type (WT) and Nrf2 knockout (KO)) was established for evaluating the effects of Q-SD in vivo. Q-SD more potently reduced retinal pigment epithelium sediments and Bruch's membrane thickness than QT and Q-PC at 200 mg/kg in Nrf2 WT mice and did not work in Nrf2 KO mice at the same dosage. Additionally, Q-SD significantly decreased ROS and MDA contents and restored SOD, GSH-PX, and CAT activities of serum and retinal tissues in Nrf2 WT mice, but not in Nrf2 KO mice. Furthermore, Q-SD more potently increased Nrf2 mRNA expression and stimulated its nuclear translocation in retinal tissues of Nrf2 WT mice. Q-SD significantly increased the expression of Nrf2 target genes HO-1, HQO-1, and GCL of retinal tissues in Nrf2 WT mice, not in Nrf2 KO mice. Altogether, Q-SD had improved physicochemical and pharmacokinetic properties compared to QT and Q-PC and exhibited more potent protective effects on retina oxidative injury in vivo. These effects were associated with activation of Nrf2 signaling and upregulation of antioxidant enzymes.

19.
Nat Commun ; 10(1): 4492, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582802

RESUMO

Drug delivery with nanocarriers relies on the interaction of individual nanocarriers with the cell surface. For lipid-based NCs, this interaction uniquely involves a process of membrane fusion between the lipid bilayer that makes up the NC and the cell membrane. Cubosomes have emerged as promising fusogenic NCs, however their individual interactions had not yet been directly observed due to difficulties in achieving adequate resolution or disentangling multiple interactions with common characterization techniques. Moreover, many studies on these interactions have been performed under static conditions which may not mimic the actual transport of NCs. Herein we have observed fusion of lipid cubosome NCs with lipid bilayers under flow. Total internal reflection microscopy has allowed visualisation of the fusion event which was sensitive to the lipid compositions and rationalized by lipid diffusion. The fusion event in supported lipid bilayers has been compared with those in cells, revealing a distinct similarity in kinetics.


Assuntos
Membrana Celular/metabolismo , Portadores de Fármacos/farmacologia , Microscopia Intravital/métodos , Fusão de Membrana , Animais , Linhagem Celular , Membrana Celular/ultraestrutura , Portadores de Fármacos/química , Células Epiteliais , Fibroblastos , Humanos , Bicamadas Lipídicas/metabolismo , Lipídeos/química , Camundongos , Microscopia de Força Atômica , Microscopia de Interferência , Nanopartículas/química , Células-Tronco , Imagem com Lapso de Tempo
20.
J Immunol Res ; 2019: 3979352, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583256

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is the major pathogen responsible for community and hospital bacterial infections. Sublancin, a glucosylated antimicrobial peptide isolated from Bacillus subtilis 168, possesses antibacterial infective effects. In this study, we investigated the role and anti-infection mechanism of sublancin in a mouse model of MRSA-induced sublethal infection. Sublancin could modulate innate immunity by inducing the production of IL-1ß, IL-6, TNF-α, and nitric oxide, enhancing phagocytosis and MRSA-killing activity in both RAW264.7 cells and mouse peritoneal macrophages. The enhanced macrophage function by the peptide in vitro correlated with stronger protective activity in vivo in the MRSA-invasive sublethal infection model. Macrophage activation by sublancin was found to be partly dependent on TLR4 and the NF-κB and MAPK signaling pathways. Moreover, oral administration of sublancin increased the frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes. The protective activity of sublancin was associated with in vivo augmenting phagocytic activity of peritoneal macrophages and partly improving T cell-mediated immunity. Macrophages thus represent a potentially pivotal and novel target for future development of innate defense regulator therapeutics against S. aureus infection.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Macrófagos/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Animais , Biomarcadores , Citocinas/metabolismo , Feminino , Macrófagos/imunologia , Staphylococcus aureus Resistente à Meticilina/imunologia , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Transdução de Sinais , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/imunologia
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