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1.
Nat Commun ; 11(1): 932, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071305

RESUMO

Regulation of male sexual differentiation by a Y chromosome-linked male determining factor (M-factor) is one of a diverse array of sex determination mechanisms found in insects. By deep sequencing of small RNAs from Bactrocera dorsalis early embryos, we identified an autosomal-derived microRNA, miR-1-3p, that has predicted target sites in the transformer gene (Bdtra) required for female sex determination. We further demonstrate by both in vitro and in vivo tests that miR-1-3p suppresses Bdtra expression. Injection of a miR-1-3p mimic in early embryos results in 87-92% phenotypic males, whereas knockdown of miR-1-3p by an inhibitor results in 67-77% phenotypic females. Finally, CRISPR/Cas9-mediated knockout of miR-1-3p results in the expression of female-specific splice variants of Bdtra and doublesex (Bddsx), and induced sex reversal of XY individuals into phenotypic females. These results indicate that miR-1-3p is required for male sex determination in early embryogenesis in B. dorsalis as an intermediate male determiner.

2.
Sensors (Basel) ; 20(3)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32045985

RESUMO

Multi-radio technology is regarded as a promising way to improve the performance of Wireless Sensor Networks (WSNs) and has attracted much attention of researchers. It is very important to reduce energy consumption and to prolong the lifetime of Multi-Radio WSNs (MR-WSNs), since the node is generally battery-operated in MR-WSN environments. In this paper, two typical types of energy consumption process, the transmitting energy consumption and idle listening energy consumption, are analyzed firstly. Based on the above analysis, the energy consumption model of multi-radio nodes is built, and then it is considered as the optimization objective for the minimization energy consumption of multi-radio nodes. Furthermore, the heuristic optimal energy consumption task scheduling strategy based on the Particle Swarm Optimization (PSO) algorithm is proposed, and then the detailed steps of the proposed strategy are presented. Finally, the effectiveness and performance of the proposed strategy are evaluated through practical experiments and simulations. Evaluation results show that the proposed strategy outperforms some other algorithms, in terms of energy consumption, network lifetime, and tasks extensibility.

3.
Molecules ; 25(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012896

RESUMO

Bombyx Batryticatus (BB) is a known traditional Chinese medicine (TCM) utilized to treat convulsions, epilepsy, cough, asthma, headaches, etc. in China for thousands of years. This study is aimed at investigating optimum extraction of protein-rich extracts from BB (BBPs) using response surface methodology (RSM) and exploring the protective effects of BBPs against nerve growth factor (NGF)-induced PC12 cells injured by glutamate (Glu) and their underlying mechanisms. The results indicated optimum process of extraction was as follows: extraction time 1.00 h, ratio of liquid to the raw material 3.80 mL/g and ultrasonic power 230.0 W. The cell viability of PC12 cells stimulated by Glu was determined by CCK-8 assay. The levels of γ-aminobutyric (GABA), interleukin-1ß (IL-1ß), interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT) and glucocorticoid receptor alpha (GR) in PC12 cells were assayed by ELISA. Furthermore, the Ca2+ levels in PC12 cells were determined by flow cytometry analysis. Protein and mRNA expressions of GABAA-Rα1, NMDAR1, GAD 65, GAD 67, GAT 1 and GAT 3 in PC12 cells were evaluated by real-time polymerase chain reaction (RT-PCR) and Western blotting assays. Results revealed that BBPs decreased toxic effects due to Glu treatment and decreased Ca2+ levels in PC12 cells. After BBPs treatments, levels of GABA and 5-HT were increased and contents of TNF-α, IL-4 and IL-1ß were decreased in NGF-induced PC12 cells injured by Glu. Moreover, BBPs up-regulated the expressions of GABAA-Rα1, GAD 65 and GAD 67, whereas down-regulated that of NMDAR1 GAT 1 and GAT 3. These findings suggested that BBPs possessed protective effects on NGF-induced PC12 cells injured by Glu via γ-Aminobutyric Acid (GABA) signaling pathways, which demonstrated that BBPs has potential anti-epileptic effect in vitro. These findings may be useful in the development of novel medicine for the treatment of epilepsy.

5.
Genes (Basel) ; 11(2)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023848

RESUMO

Essential genes are a group of genes that are indispensable for cell survival and cell fertility. Studying human essential genes helps scientists reveal the underlying biological mechanisms of a human cell but also guides disease treatment. Recently, the publication of human essential gene data makes it possible for researchers to train a machine-learning classifier by using some features of the known human essential genes and to use the classifier to predict new human essential genes. Previous studies have found that the essentiality of genes closely relates to their properties in the protein-protein interaction (PPI) network. In this work, we propose a novel supervised method to predict human essential genes by network embedding the PPI network. Our approach implements a bias random walk on the network to get the node network context. Then, the node pairs are input into an artificial neural network to learn their representation vectors that maximally preserves network structure and the properties of the nodes in the network. Finally, the features are put into an SVM classifier to predict human essential genes. The prediction results on two human PPI networks show that our method achieves better performance than those that refer to either genes' sequence information or genes' centrality properties in the network as input features. Moreover, it also outperforms the methods that represent the PPI network by other previous approaches.

6.
J Ethnopharmacol ; : 112649, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32068140

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Calculus bovis (C. bovis), as a widespread known traditional animal drug in China and Japan, has been widely used to treat various diseases for a long history, including high fever, convulsion and stroke. The aim of the present paper is conducted to comprehensively review the knowledge about C. bovis in traditional usages, origin, chemical constituents, pharmacological activities and toxicology, which is to seek the applicable substitute of NCB and provide potential new strategies about C. bovis. Besides, the directions and perspectives for future investigation regarding C. bovis are also discussed in the manuscript. MATERIALS AND METHODS: In this paper, traditional usages, origin, chemical constituents, pharmacology, and toxicology of C. bovis are comprehensively and systematically summarized through searching scientific databases, including Web of Science, PubMed, Sciencedirect, Springer, CNKI, Baidu Scholar and others. Besides, some classic books of Chinese herbal medicine, academic papers of MSc and PhD, local government reports as well as the state of local drug standards are also retrieved. RESULTS: Currently, C. bovis mainly comes from four sources: natural Calculus bovis (NCB), Calculus bovis sativus (CBS), Cultured calculus bovis (CCB) and Calculus bovis artifactus (CBA). Owing to their different forming process, chemical constituents of four kinds of C. bovis show the certain difference. And over 44 chemical constituents have been isolated and identified from C. bovis, mainly including bile pigments, bile acids, cholesterols and amino acids. Further investigations show a wide range of pharmacological effects on C. bovis, containing effects on the nervous system, cardiovascular system, respiratory system, digestive system, immune system and others. Furthermore, NCB and CBA shows hypotoxicity, but bilirubin of high concentrations is able to cause neurotoxicity and hearing impairment. Additionally, the data about pharmacokinetics of C. bovis still lack. CONCLUSION: CBS contains analogous types and amounts of constituents and exerts approximate therapeutic effects compared to the NCB, thus the CBS might be used as the sustainable substitute of NCB. Furthermore, configuration and concentration of bile acids and bilirubin in C. bovis are responsible for the difference of pharmacological effects in four types C. bovis. The next study should focus on the structure-function relationship of bile acids and bilirubin in C. bovis by pharmacokinetics.

7.
J Cardiothorac Surg ; 15(1): 33, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019564

RESUMO

BACKGROUND: Presently, endoscopic submucosal tunnel dissection (ESTD) has been a novel therapy for superficial esophageal neoplastic lesions (SENL), especially for circumferential neoplastic lesions. A number of studies have reported the clinical application of ESTD with promising outcomes. Therefore, we conducted a systematic review and meta-analysis to evaluated the efficacy and safety of ESTD for SENL . METHODS: From 2013 to November 2018, Pubmed, Embase and Cochrane databases were searched to determine studies reporting ESTD treatment of SENL. Weighted pooled rates (WPR) were calculated for en bloc resection, R0 resection and complication of ESTD. Risk ratios (RR) were calculated and pooled to compare the clinical outcomes of ESTD with ESD for SENL. RESULTS: A total of 9 studies involving 494 patients with 518 esophageal neoplastic lesions were included in our study. WPR for en bloc resection and R0 resection of ESTD was 97.0% (95% CI: 94.7-98.3%) and 84.1% (95% CI: 80.5-87.1%), respectively. WPR for complication was 40.0% (95% CI: 25.8-56.1%). Two studies with 265 patients compared the performance of ESTD with ESD. Pooled RR for en bloc resection and R0 resection was 1.04 (95% CI: 0.95-1.14, P = 0.42) and 1.01 (95% CI: 0.93-1.10, P = 0.73), respectively. Pooled RR for complication was 0.68 (95% CI: 0.46-1.01, P = 0.05). CONCLUSION: Our study showed that ESTD is effective for treating SENL with high en bloc resection rate and R0 resection rate, but accompanying by a relatively high complications.

8.
Reprod Sci ; 27(1): 163-171, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32046373

RESUMO

The methionine adenosyltransferase 2ß gene (Mat2b) encodes for the regulatory subunit of methionine adenosyltransferase (MAT), which catalyzes the biosynthesis of S-adenosylmethionine. MAT2B interacts with G protein-coupled receptor kinase interacting ArfGAP1 to increase the activity of extracellular signal-regulated kinases (ERKs) for the regulation of cell growth, metabolism, and differentiation. ERK activity is also essential for oocyte meiosis in mice. However, the regulatory role of MAT2B in mouse oocyte meiosis remains unclear. Accordingly, this study investigated the effect of MAT2B on mouse oocyte maturation. Immunostaining showed that MAT2B localized predominantly in the nucleus of fully grown germinal vesicle (GV) oocytes. After germinal vesicle breakdown (GVBD), MAT2B homogeneously localized in the cytoplasm. A low oocyte maturation rate was observed in Mat2b siRNA-treated oocytes. Furthermore, Mat2b knockdown repressed the phosphorylation of ERK1/2 and consequently blocked MAPK. Denuded oocytes treated with 20 µM U0126 mainly blocked MAPK phosphorylation and affected oocyte maturation. The oocytes arrested at GVBD and metaphase I (MI) by Mat2b silencing or U0126 treatment had several types of abnormal microtubule assembly. Furthermore, Mat2b knockdown or U0126 treatment resulted in the aberrant expression of six maternal transcripts, namely, Fgf8, Cdc2, Gdf9, Padi6, Polr2d, and Tecb2. To the best of our knowledge, this study is the first to demonstrate that Mat2bs play an important role in mouse oocyte maturation though MAPK signaling.

9.
Biosens Bioelectron ; 154: 112039, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32056956

RESUMO

A label-free Au NPs-enhanced surface plasmon resonance (SPR) sensor was developed for the ultrasensitive detection of heparin based on competitive adsorption behavior of heparin and Au NPs on the poly (dimethyl-diallylammonium chloride) (PDDA)-modified optical fiber surface and the corresponding change in the resonance wavelength of SPR. Due to the high affinity between heparin and PDDA, the present senor shows good analytical performance with respect to heparin detection. Two obvious advantages of the proposed heparin sensor over other reported methods are: its much wider linear concentration range (10-6-10-10 g/mL) and lower limit of detection (0.0257 ng/mL). The analysis of heparin in serum demonstrated that the present sensor exhibited high sensitivity and selectivity. It should be noted that the sensing strategy takes advantage of a portable fiber-optic SPR sensing system and avoids the need for complex processes for labeled-Au NPs, and thus the present sensor promises to be a practical tool for the point-of-care monitoring of heparin.

10.
J Diabetes Res ; 2020: 4981814, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32083135

RESUMO

As a chronic metabolic disease, diabetes mellitus (DM) is broadly characterized by elevated levels of blood glucose. Novel epidemiological studies demonstrate that some diabetic patients have an increased risk of developing dementia compared with healthy individuals. Alzheimer's disease (AD) is the most frequent cause of dementia and leads to major progressive deficits in memory and cognitive function. Multiple studies have identified an increased risk for AD in some diabetic populations, but it is still unclear which diabetic patients will develop dementia and which biological characteristics can predict cognitive decline. Although few mechanistic metabolic studies have shown clear pathophysiological links between DM and AD, there are several plausible ways this may occur. Since AD has many characteristics in common with impaired insulin signaling pathways, AD can be regarded as a metabolic disease. We conclude from the published literature that the body's diabetic status under certain circumstances such as metabolic abnormalities can increase the incidence of AD by affecting glucose transport to the brain and reducing glucose metabolism. Furthermore, due to its plentiful lipid content and high energy requirement, the brain's metabolism places great demands on mitochondria. Thus, the brain may be more susceptible to oxidative damage than the rest of the body. Emerging evidence suggests that both oxidative stress and mitochondrial dysfunction are related to amyloid-ß (Aß) pathology. Protein changes in the unfolded protein response or endoplasmic reticulum stress can regulate Aß production and are closely associated with tau protein pathology. Altogether, metabolic disorders including glucose/lipid metabolism, oxidative stress, mitochondrial dysfunction, and protein changes caused by DM are associated with an impaired insulin signal pathway. These metabolic factors could increase the prevalence of AD in diabetic patients via the promotion of Aß pathology.

11.
Curr Biol ; 30(2): R89-R91, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31962086

RESUMO

Amino acid signaling through the Rag GTPases promotes mTORC1 lysosomal localization and subsequent activation. Two new cryo-EM structures examine the architecture of the Rag GTPase heterodimers complexed with mTORC1.

12.
Nutrients ; 12(1)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952251

RESUMO

Ganpu tea is an emerging tea drink produced from Pu-erh tea and the pericarp of Citrus reticulate Chachi (GCP). Recently, it has been increasingly favored by consumers due to the potential health effects and special taste. However, information concerning its chemical profile and biological activities is scarce. In this work, a total of 92 constituents were identified in hot-water extracts of Ganpu tea with ultra-high performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). Moreover, the antioxidative and gut microbiota modulatory properties of Ganpu tea were investigated in rats after long-term dietary consumption. Ganpu tea and GCP could significantly enhance the activities of superoxide dismutase (SOD) by 13.4% (p < 0.05) and 15.1% (p < 0.01), as well as the activities of glutathione peroxidase (GSH-Px) by 16.3% (p < 0.01) and 20.5% (p < 0.01), respectively. Both showed better antioxidant capacities than Pu-erh tea. Ganpu tea increased the abundance of Bifidobacterium, Lactobacillus, and Lactococcus, suggesting the potential of Ganpu tea in modulating the gut microbiota to benefit human health. The obtained results provide essential information for further investigation of Ganpu tea.

13.
Sensors (Basel) ; 20(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979225

RESUMO

The spatiotemporal crustal non-tectonic deformation caused by ocean tidal loading (OTL) can reach the centimeters scale in coastal land areas. The temporal variation of the site OTL displacements can be estimated by the global positioning system (GPS) technique, but its spatial variation needs to be further determined. In this paper, in order to analyze the spatial characteristics of the OTL displacements, we propose a multi-scale decomposition method based on signal spatial characteristics to derive the OTL displacements from differential interferometric synthetic aperture radar (D-InSAR) measurements. The method was tested using long-term advanced synthetic aperture radar (ASAR) data and GPS reference site data from the Los Angeles Basin in the United States, and we compared the results with the FES2014b tide model. The experimental results showed that the spatial function of the OTL displacements in an ASAR image can be represented as a higher-order polynomial function, and the spatial trends of the OTL displacements determined by the InSAR and the GPS techniques are basically consistent with the FES2014b tide model. The root-mean-square errors of the differences between the spatial OTL displacements of these two methods and the FES2014b tide model are less than 0.8 mm. The results indicate that the OTL displacement extracted from InSAR data can accurately reflect the spatial characteristics of the OTL effect, which will help to improve the spatial resolution and accuracy of the OTL displacement in coastal areas.

14.
ACS Nano ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31951384

RESUMO

Terahertz technology promises broad applications, which calls for terahertz electromagnetic interference (EMI) shielding materials to alleviate radiation pollution. 2D transition metal carbides and/or nitrides (MXenes) with metallic conductivity are promising for EMI shielding, but simultaneously realizing light weight, high stability, and foldability in a MXene shielding material to meet the requirements of increasingly popular portable and wearable equipment has remained a great challenge. Herein, an ion-diffusion-induced gelation method is demonstrated to synthesize free-standing, light-weight, foldable, and highly stable MXene foams, in which MXene sheets are cross-linked by multivalent metal ions and graphene oxide to form an oriented porous structure. The method is highly efficient, controllable, and versatile for scalable generation of functional 3D MXene structures with arbitrary shapes and synergistic properties. The distinctive cross-linked porous structure endows the light-weight MXene foam with good foldability, outstanding durability and stability in wet environments, and an excellent terahertz shielding effectiveness of 51 dB at a small thickness of 85 µm. This work not only provides an insight for the on-target design of high-performance terahertz shielding materials but also expands the applications of MXenes in 3D macroscopic form.

15.
J Am Chem Soc ; 142(4): 2068-2073, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31927987

RESUMO

While the mechanism of the P450-catalyzed oxidative hydroxylation of organic compounds has been studied in detail for many years, less is known about sulfoxidation. Depending upon the structure of the respective substrate, heme-Fe═O (Cpd I), heme-Fe(III)-OOH (Cpd 0), and heme-Fe(III)-H2O2 (protonated Cpd 0) have been proposed as reactive intermediates. In the present study, we consider the transformation of isosteric substrates via sulfoxidation and oxidative hydroxylation, respectively, catalyzed by regio- and enantioselective mutants of P450-BM3 which were constructed by directed evolution. 1-Thiochromanone and 1-tetralone were used as the isosteric substrates because, unlike previous studies involving fully flexible compounds such as thia-fatty acids and fatty acids, respectively, these compounds are rigid and cannot occur in a multitude of different conformations and binding modes in the large P450-BM3 binding pocket. The experimental results comprising activity and regio- and enantioselectivity, flanked by molecular dynamics computations within a time scale of 300 ns and QM/MM calculations of transition-state energies, unequivocally show that heme-Fe═O (Cpd I) is the common catalytically active intermediate in both sulfoxidation and oxidative hydroxylation.

16.
Nanotechnology ; 31(16): 165704, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-31891932

RESUMO

Recently, Bi2O2Se was revealed as a promising two-dimensional (2D) semiconductor for next generation electronics, due to its moderate bandgap size, high electron mobility and pronounced ambient stability. Meanwhile, it has been predicted that high-quality Bi2O2Se-related heterostructures may possess exotic physical phenomena, such as piezoelectricity and topological superconductivity. Herein, we report the first successful heteroepitaxial growth of Bi2O2Se films on SrTiO3 substrates via pulsed laser deposition (PLD) method. Films obtained under optimal conditions show an epitaxial growth with the c axis perpendicular to the film surface and the a and b axes parallel to the substrate. The growth mode transition to three-dimensional (3D) island from quasi-2D layer of the heteroepitaxial Bi2O2Se films on SrTiO3 (001) substrates is observed as prolonging deposition time of films. The maximum value of electron mobility reaches 160 cm2 V-1 s-1 at room temperature in a 70 nm thick film. The thickness dependent mobility provides evidence that interface-scattering is likely to be the limiting factor for the relatively low electron mobility at low temperature, implying that the interface engineering as an effective method to tune the low temperature electron mobility. Our work suggests the epitaxial Bi2O2Se films grown by PLD are promising for both fundamental study and practical applications.

17.
J Agric Food Chem ; 68(4): 1101-1109, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31904947

RESUMO

ε-Poly-l-lysine (ε-PL) consists of 25-35 lysine residues which are linked by an isopeptide bond formed by dehydration condensation of α-carboxyl and ε-amino groups and has good antibacterial activity and broad-spectrum inhibition range. However, there is no clear conclusion about the structure and antibacterial mechanism of ε-PL in aqueous solution. Herein, a high purity of ε-PL was prepared using Amberlite IRC-50 ion-exchange resin. Membrane filtration and dynamic light scattering were used to study the variations of ε-PL aggregation in aqueous solution with pH value. The conformational changes and antibacterial activities of ε-PL and carbamoylated ε-PL in different water environments were studied with circular dichroism (CD) and inhibition zone. The structural changes during the spray-drying process were determined by Fourier transform infrared spectroscopy. The results indicated that the side chain amino charge played a decisive role in the ε-PL conformation and aggregation. ε-PL exhibited the properties of a ß-sheet during spray drying from acidic liquids to solids. The cation enhanced the antibacterial activity of ε-PL but did not play a key role. Instead, the backbone of ε-PL might determine the mechanism of ε-PL antibacterial.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Polilisina/química , Polilisina/farmacologia , Antibacterianos/metabolismo , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Transição de Fase , Polilisina/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Streptomyces/química , Streptomyces/metabolismo
18.
J Vet Sci ; 21(1): e13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31940692

RESUMO

Currently, the systems for culturing buffalo spermatogonial stem cells (SSCs) in vitro are varied, and their effects are still inconclusive. In this study, we compared the effects of culture systems with undefined (foetal bovine serum) and defined (KnockOut Serum Replacement) materials on the in vitro culture of buffalo SSC-like cells. Significantly more DDX4- and UCHL1-positive cells (cultured for 2 days at passage 2) were observed in the defined materials culture system than in the undefined materials system (p < 0.01), and these cells were maintained for a longer period than those in the culture system with undefined materials (10 days vs. 6 days). Furthermore, NANOS2 (p < 0.05), DDX4 (p < 0.01) and UCHL1 (p < 0.05) were expressed at significantly higher levels in the culture system with defined materials than in that with undefined materials. Induction with retinoic acid was used to verify that the cultured cells maintained SSC characteristics, revealing an SCP3⁺ subset in the cells cultured in the defined materials system. The expression levels of Stra8 (p < 0.05) and Rec8 (p < 0.01) were significantly increased, and the expression levels of ZBTB16 (p < 0.01) and DDX4 (p < 0.05) were significantly decreased. These findings provided a clearer research platform for exploring the mechanism of buffalo SSCs in vitro.

19.
Exp Mol Pathol ; 113: 104375, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917288

RESUMO

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes mellitus.The main pathological features of DN include glomerular sclerosis and renal tubular interstitial fibrosis, which results in epithelial mesenchymal transition (EMT) and excessive extracellular matrix (ECM) deposition.Transforming growth factor-ß1(TGF-ß1) is a critical factor that regulates the manifestation of renal fibrosis.Smad2 and Smad3 are the main downstream of the TGF-ß1 pathway. Ski-related novel protein N(SnoN) is a negative regulator of TGF-ß1, and inhibits the activation of the TGF-ß1/Smad2/3 signalling pathway. In this study, the expression of Smad2 and Smad3 proteins, SnoN mRNA, SnoN proteins, and the ubiquitination levels of SnoN were determined in DN rats and renal tubular epithelial cells(NRK52E cells). Knockdown and overexpression of Smad2 or Smad3 in NRK52E cells were used to investigate the specific roles of Smad2 and Smad3 in the development of high glucose-induced renal tubular fibrosis, with a specific focus on their effect on the regulation of SnoN expression. Our study demonstrated that Smad3 could inhibit SnoN expression and increase ECM deposition in NRK52E cells, to promote high glucose-induced renal tubular fibrosis. In contrast, Smad2 could induce SnoN expression and reduce ECM deposition, to inhibit high glucose-induced fibrosis. The underlying mechanism involves regulation of SnoN expression. These findings provide a novel mechanism to understanding the significant role of the TGF-ß1/ Smad2/3 pathway in DN.

20.
Environ Pollut ; 259: 113923, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31935612

RESUMO

The emerging flame retardants pentabromobenzene (PBB) has been frequently detected in recent years and may pose exposure risks to wild animals and human beings. In this study, the inflation of posterior swim bladder of zebrafish larvae was used as an endpoint to study the developmental toxicity and putative mechanisms associated with PBB toxicity. Our results showed that embryonic exposure to PBB could significantly inhibit the inflation of posterior swim bladders. Reduced T3 levels and transcriptional changes of crh and pomc were observed in PBB treated zebrafish larvae at 120 hpf. However, key regulators of thyroid and adrenocortical system involved in the synthesis (tsh), biological conversion (ugt1ab, dio2) and functional regulation (trα, trß, gr) showed no significant changes. Further data revealed that prlra was the only gene that was altered among the detected genes at 96 h post fertilization (hpf). At 120 hpf, the morphology of swim bladder indicated deflation in treatments at 0.25 µM and higher. In addition, the mRNA levels of anxa5, prlra, prlrb, atp1b2 and slc12a10 were all significantly changed at 120 hpf. Taken together, we suppose that embryonic exposure to PBB inhibited the inflation of swim bladder in zebrafish probably via prlra mediated pathways. The observed changes of thyroid and adrenocortical parameters might be indirect effects evoked by PBB exposure. Overall, our results provide important data and indications for future toxicological study and risk assessment of the emerging flame retardants PBB.

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