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1.
Int J Nanomedicine ; 15: 9657-9668, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299310

RESUMO

Purpose: To evaluate the effects of ZnO NPs on bone growth in rats and explore the possible mechanisms of action. Materials and Methods: Three-week-old male rats received ultrapure water or 68, 203, and 610 mg/kg zinc oxide nanoparticles (ZnO NPs) for 28 days, orally. Results: The high-dosage groups caused significant differences in weight growth rate, body length, and tibia length (P<0.05), all decreasing with increased ZnO NP dosage. There were no significant differences in body mass index (BMI) (P>0.05). The zinc concentration in liver and bone tissue increased significantly with increased ZnO NP dosage (P<0.05). Clearly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were observed in the 610 mg/kg ZnO NP group (P>0.05), whereas alkaline phosphatase (ALP) increased in the 610 mg/kg ZnO NP group (P<0.05). Significant differences in insulin-like growth factor type 1 (IGF-1) levels and a decrease in calcium (Ca) levels were observed in 203 and 610 mg/kg ZnO NP groups (P<0.05). Phosphorus (P) levels increased and the Ca/P ratio decreased in the 610 mg/kg ZnO NP group (P<0.05). Micro-computed tomography (micro-CT) of the tibia demonstrated signs of osteoporosis, such as decreased bone density, little trabecular bone structure and reduced cortical bone thickness. Micro-CT data further demonstrated significantly decreased bone mineral density (BMD), trabecular number (Tb.N), and relative bone volume (BV/TV) with increasing dosage of ZnO NPs. Osteoprotegerin (OPG) expression and the ratio of OPG to receptor activator of nuclear factor-κB ligand (RANKL) were statistically lower in the 610 mg/kg ZnO NP group (P<0.05), whereas RANKL expression did not change significantly (P>0.05). Conclusion: We infer that ZnO NPs affect bone growth in young rats directly or indirectly by altering IGF-1 levels. Overall, the results indicate that ZnO NPs promote osteoclast activity and increase bone loss through the OPG/RANK/RANKL/IGF-1 pathway.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Nanopartículas/química , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Tíbia/efeitos dos fármacos , Óxido de Zinco/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Feminino , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos , Tíbia/diagnóstico por imagem , Tíbia/metabolismo , Tíbia/fisiologia , Microtomografia por Raio-X , Óxido de Zinco/química
2.
Artigo em Inglês | MEDLINE | ID: mdl-33216724

RESUMO

Accurate segmentation of lung cancer in pathology slides is a critical step in improving patient care. We proposed the ACDC@LungHP (Automatic Cancer Detection and Classification in Whole-slide Lung Histopathology) challenge for evaluating different computer-aided diagnosis (CADs) methods on the automatic diagnosis of lung cancer. The ACDC@LungHP 2019 focused on segmentation (pixel-wise detection) of cancer tissue in whole slide imaging (WSI), using an annotated dataset of 150 training images and 50 test images from 200 patients. This paper reviews this challenge and summarizes the top 10 submitted methods for lung cancer segmentation. All methods were evaluated using metrics using the precision, accuracy, sensitivity, specificity, and DICE coefficient (DC). The DC ranged from 0.7354±0.1149 to 0.8372±0.0858. The DC of the best method was close to the inter-observer agreement (0.8398±0.0890). All methods were based on deep learning and categorized into two groups: multi-model method and single model method. In general, multi-model methods were significantly better (p<0.01) than single model methods, with mean DC of 0.7966 and 0.7544, respectively. Deep learning based methods could potentially help pathologists find suspicious regions for further analysis of lung cancer in WSI.

3.
PLoS One ; 15(11): e0242624, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33211753

RESUMO

Synonymous codon usage bias (SCUB) of both nuclear and organellar genes can mirror the evolutionary specialization of plants. The polyploidization process exposes the nucleus to genomic shock, a syndrome which promotes, among other genetic variants, SCUB. Its effect on organellar genes has not, however, been widely addressed. The present analysis targeted the chloroplast genomes of two leading polyploid crop species, namely cotton and bread wheat. The frequency of codons in the chloroplast genomes ending in either adenosine (NNA) or thymine (NNT) proved to be higher than those ending in either guanidine or cytosine (NNG or NNC), and this difference was conserved when comparisons were made between polyploid and diploid forms in both the cotton and wheat taxa. Preference for NNA/T codons was heterogeneous among genes with various numbers of introns and was also differential among the exons. SCUB patterns distinguished tetraploid cotton from its diploid progenitor species, as well as bread wheat from its diploid/tetraploid progenitor species, indicating that SCUB in the chloroplast genome partially mirrors the formation of polyploidies.


Assuntos
Uso do Códon , Códon , Genoma de Cloroplastos , Gossypium/genética , Poliploidia , Triticum/genética , Éxons
4.
Rapid Commun Mass Spectrom ; : e9011, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232557

RESUMO

RATIONALE: The research area of ion clusters has helped to enrich the study of chemical bonding theory, clarify the crystal nucleation process and investigate the cluster ion-molecule reactions. Mass spectrometry technique, especially high-resolution MS, is an important method for investigating ion clusters in the gas phase. As polyoxometalates have been attracting considerable interest in biochemistry, medicine and materials science due to their excellent structural and electronic features and it is important to characterize these clusters by MS. METHODS: Singly negatively charged molybdenum-containing and tungsten-containing ion clusters with different matrices were produced by Keggin-type silicopolyoxometalate anions under matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). RESULTS: The matrices displayed an obvious influence on the formation of ion clusters. It was found that the molybdenum-containing ion species [(HSiO3 )(MoO3 )n ]- , [(SiO2 )m (MoO3 )n (H2 O)x ]-• , [(OH)(MoO3 )n ]-• [(MoO3 )n ]-• and [Hx SiMoy Oz ]- were the main ion series in the mass spectra. For the tungsten-containing ion cluster, [(HSiO3 )(WO3 )n ]- , [(C8 H5 Om )(WO3 )n (H2 O)x ]- , [(OH)(WO3 )n ]- , and [(WO3 )n ]-• were the main ion species in the mass spectra, and a series of organic-inorganic hybrid tungsten-containing ion clusters [(C8 H5 Om )(WO3 )n (H2 O)x ]- were generated by the interaction of DHAP and THAP matrices with tungstate anions. Furthermore, the most abundance species (magic number) in each ion series indicated that they might adopt more stable structures than other relevant clusters. CONCLUSIONS: Keggin-type silicopolyoxometalate anions can produce several series of singly charged molybdenum-containing/tungsten-containing ion clusters in negative-ion generating mode under MALDI conditions. It is proposed that the "Lucky Survivors" hypothesis may be used to illustrate the generation of ion clusters in the gas phase during the early stages of plume expansion. In addition, clear evidences of hydrogen transfer and electron capture to POMs was found in the obtained MALDI mass spectra. These results highlight the utility of the MALDI-FT method for obtaining novel ion clusters and also show the stability of these clusters.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33180726

RESUMO

Collecting and analyzing anonymous personal information is required as a part of data analysis processes, such as medical diagnosis and restaurant recommendation. Such data should ostensibly be stored so that specific individual information cannot be disclosed. Unfortunately, inference attacks---integrating background knowledge and intelligent models---hinder classic sanitization techniques like syntactic anonymity and differential privacy from exhaustively protecting sensitive information. As a solution, we introduce a three-stage approach empowered within a visual interface, which depicts underlying inferences behaviors via Bayesian Network and supports customized defense against inference attacks from unknown adversaries. In particular, our approach visually explains the process details of the underlying privacy preserving models, allowing users to verify if the results sufficiently satisfy the requirements of privacy preservation. We demonstrate the effectiveness of our approach through two case studies and expert reviews.

6.
Anal Chem ; 92(23): 15639-15646, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33179904

RESUMO

Vascular endothelial cells (ECs) are natively exposed to dynamic cyclic stretch and respond to it by the production of vasoactive molecules. Among them, reactive oxygen species (ROS) are closely implicated to the endothelial function and vascular homeostasis. However, the dynamic monitoring of ROS release during endothelial mechanotransduction remains a steep challenge. Herein, we developed a stretchable electrochemical sensor by decoration of uniform and ultrasmall platinum nanoparticles (Pt NPs) on gold nanotube (Au NT) networks (denoted as Au@Pt NTs). The orchestrated structure exhibited prominent electrocatalytic property toward the oxidation of hydrogen peroxide (H2O2) (as the most stable ROS) while maintaining excellent mechanical compliance of Au NT networks. Moreover, the favorable biocompatibility of Au NTs and Pt NPs promoted the adhesion and proliferation of ECs cultured thereon. These allowed in situ inducing ECs mechanotransduction and synchronously real-time monitoring of H2O2 release. Further investigation revealed that the production of H2O2 was positively correlated with the applied mechanical strains and could be boosted by other coexisting pathogenic factors. This indicates the great prospect of our proposed sensor in exploring ROS-related signaling for the deep understanding of cell mechanotransduction and vascular disorder.

7.
Medicine (Baltimore) ; 99(43): e22679, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120759

RESUMO

Gestational diabetes mellitus (GDM) is a kind of chronic inflammatory condition with carbohydrate metabolism disorder. Interleukin-1beta (IL-1ß) plays an important role in inflammatory response, but its role in GDM development remains unknown. The aim of this study was to analyze the association between Interleukin 1beta (IL1B) rs1143623 and rs16944 polymorphisms and susceptibility to GDM.In total, 300 pregnant women with GDM and 261 healthy pregnant women were included in the study. In both groups, single nucleotide polymorphism (SNP) rs1143623 and rs16944 were analyzed by using snapshot technology. IL-1ß serum values were determined by ELISA.Serum IL-1ß levels involvement in GDM development. According to the results, we found the association between the IL1B rs1143623 polymorphism and susceptibility to GDM. In further analysis, IL1B rs1143623 GG genotype had a higher level of total cholesterol (TCHO) and lower level of high density lipoprotein (HDL) in GDM patients compared with the CC/GC genotypes. However, there were no statistically significant difference between the GDM and healthy control groups in terms of rs16944 polymorphism.Our results indicated that rs1143623 in IL1B gene may lead to GDM in the southwest of china. However, no significant difference was found between GDM and rs16944. The rs1143623 genotype may significantly impact the fat metabolism, especially the levels of TCHO and HDL. We believe that our findings will contribute to understanding of the etiology and possible novel prognostic markers for GDM.


Assuntos
Diabetes Gestacional/genética , Interleucina-1beta/sangue , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez
8.
Mikrochim Acta ; 187(11): 612, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064202

RESUMO

This review (with 106 references) summarizes the latest progress in the synthesis, properties and biomedical applications of gold nanotubes (AuNTs). Following an introduction into the field, a first large section covers two popular AuNTs synthesis methods. The hard template method introduces anodic alumina oxide template (AAO) and track-etched membranes (TeMs), while the sacrificial template method based on galvanic replacement introduces bimetallic, trimetallic AuNTs and AuNT-semiconductor hybrid materials. Then, the factors affecting the morphology of AuNTs are discussed. The next section covers their unique surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS) and their catalytic properties. This is followed by overviews on the applications of AuNTs in biosensors, protein transportation, photothermal therapy and imaging. Several tables are presented that give an overview on the wealth of synthetic methods, morphology factors and biological application. A concluding section summarizes the current status, addresses current challenges and gives an outlook on potential applications of AuNTs in biochemical detection and drug delivery.Graphical abstract.

9.
Nat Commun ; 11(1): 5183, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33056981

RESUMO

Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome data from 702 neuroblastoma samples. Forty percent of samples harbor at least one recurrent driver gene alteration and most aberrations, including MYCN, ATRX, and TERT alterations, differ in frequency by age. MYCN alterations occur at median 2.3 years of age, TERT at 3.8 years, and ATRX at 5.6 years. COSMIC mutational signature 18, previously associated with reactive oxygen species, is the most common cause of driver point mutations in neuroblastoma, including most ALK and Ras-activating variants. Signature 18 appears early and is continuous throughout disease evolution. Signature 18 is enriched in neuroblastomas with MYCN amplification, 17q gain, and increased expression of mitochondrial ribosome and electron transport-associated genes. Recurrent FGFR1 variants in six patients, and ALK N-terminal structural alterations in five samples, identify additional patients potentially amenable to precision therapy.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Neuroblastoma/genética , Adolescente , Adulto , Fatores Etários , Quinase do Linfoma Anaplásico/genética , Criança , Pré-Escolar , Estudos de Coortes , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Conjuntos de Dados como Assunto , Transporte de Elétrons/genética , Exoma/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Ribossomos Mitocondriais , Mutação , Neuroblastoma/patologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Proteínas Ribossômicas/genética , Transcriptoma/genética , Sequenciamento Completo do Genoma , Adulto Jovem
10.
Plants (Basel) ; 9(11)2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33113801

RESUMO

The lotus (Nelumbo nucifera) is one of the most popular aquatic plants in Asia, and has emerged as a novel model for studying flower and rhizome development, and primary and secondary metabolite accumulation. Here, we developed a highly efficient callus induction system for the lotus by optimizing a series of key factors that affect callus formation. The highest efficient callus production was induced on immature cotyledon and embryo explants grown on Murashige and Skoog (MS) basal medium containing an optimized combination of 3 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.5 mg/L 6-benzylaminopurine (6-BA). In addition, lotus callus induction was proven to be influenced by lotus genotypes, light conditions, the developmental stages of explants and the time of explant sampling. Collecting immature cotyledons from seeds of the genotype "Shilihe 1", at 9 days post pollination, and to culture the explants in darkness, are proposed as the optimum conditions for lotus callus induction. Interestingly, highly efficient callus induction was also observed in explants of immature embryo derived aseptic seedlings; and a small amount of lotus benzylisoquinoline alkaloid (BIA) and obvious expression of BIA biosynthetic genes were detected in lotus callus.

11.
Huan Jing Ke Xue ; 41(10): 4690-4700, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124402

RESUMO

To realize the comprehensive utilization of resources of moutai-flavor vinasse and improve the nitrogen efficiency of yellow soil, a field culture experiment was carried out to study the effects of short-term application of vinasse biochar on nitrogen availability and bacterial community structure diversity in yellow soil of Guizhou by setting 5 biochar dosages of 0% (MB0), 0.5% (MB0.5), 1.0% (MB1.0), 2.0% (MB2.0), and 4.0% (MB4.0). The results showed that the total nitrogen(TN) and nitrate nitrogen(NN) content in the soil increased by 35.79%-365.26% and 122.96%-171.80%, the microbial biomass nitrogen (MBN) content decreased by 34.10%-59.95%, and the AN/TN, NN/TN, and MBN/TN exhibited a decreasing trend with an increase in the amount of biochar applied. The application of vinasse biochar significantly reduced the number of OTU and community richness and diversity of soil bacteria; the influence degree increased with an increase in the application amount of vinasse biochar. In comparison with the MB0 treatment, the application of biochar significantly changed the soil bacterial community structure. The relative abundance of Bacteroidetes increased by 1.76-2.11 times with an increase in the biochar application. However, the relative abundance of Acidobacteria, Chloroflexi, Gemmatimonadetes, Planctomycetes, Armatimonadetes, Thaumarchaeota, and Nitrospirae decreased to different degrees, with the most significant decrease in the MB4.0 treatment. The application of vinasse biochar increased the relative abundance of certain soil functional bacteria, such as Streptomyces and Pusillimonas, and simultaneously also decreased the relative abundance of the dominant bacteria, such as Lysobacter and Gemmatimonas. In addition, the redundancy analysis (RDA) showed that the MBN/TN, NN, and MBN were the main cause of soil bacterial community structure change in nitrogen environment factor. The MBN/TN and MBN exhibited a significantly positive correlation with Thaumarchaeota and Nitrospira, which indicated that the short-term application of vinasse biochar can significantly reduce the abundance of ammonia-oxidizing archaea and nitrifying bacteria, inhibit the ammonia-oxidizing effect and nitrification rate of soil, and improve the availability of soil nitrogen. In summary, the short-term application of vinasse biochar can improve nitrogen nutrients, change the structure and diversity of soil bacterial community, and effectively control the risk of soil nitrogen leaching by inhibiting ammonia oxidation and nitrification of soil, to improve the availability of soil nitrogen.


Assuntos
Nitrogênio , Solo , Carvão Vegetal , Nitrogênio/análise , Microbiologia do Solo
12.
BMC Plant Biol ; 20(1): 457, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023477

RESUMO

BACKGROUND: Starch in the lotus seed contains a high proportion of amylose, which endows lotus seed a promising property in the development of hypoglycemic and low-glycemic index functional food. Currently, improving starch content is one of the major goals for seed-lotus breeding. ADP-glucose pyrophosphorylase (AGPase) plays an essential role in regulating starch biosynthesis in plants, but little is known about its characterization in lotus. RESULTS: We describe the nutritional compositions of lotus seed among 30 varieties with starch as a major component. Comparative transcriptome analysis showed that AGPase genes were differentially expressed in two varieties (CA and JX) with significant different starch content. Seven putative AGPase genes were identified in the lotus genome (Nelumbo nucifera Gaertn.), which could be grouped into two subfamilies. Selective pressure analysis indicated that purifying selection acted as a vital force in the evolution of AGPase genes. Expression analysis revealed that lotus AGPase genes have varying expression patterns, with NnAGPL2a and NnAGPS1a as the most predominantly expressed, especially in seed and rhizome. NnAGPL2a and NnAGPS1a were co-expressed with a number of starch and sucrose metabolism pathway related genes, and their expressions were accompanied by increased AGPase activity and starch content in lotus seed. CONCLUSIONS: Seven AGPase genes were characterized in lotus, with NnAGPL2a and NnAGPS1a, as the key genes involved in starch biosynthesis in lotus seed. These results considerably extend our understanding on lotus AGPase genes and provide theoretical basis for breeding new lotus varieties with high-starch content.

13.
Iran J Pharm Res ; 19(1): 436-447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922499

RESUMO

The content of polysaccharides in Tuber sinense was investigated by isolation and purification, followed with the further antioxidant studies in total reducing capacity and radical scavenging activities. The crude extract of polysaccharides was purified by dialysis, column chromatography, and High Performance Liquid Chromatography. The main components of monosaccharide (s) and molecular structure of single polysaccharide were studied by using methylation, GC-MS, and NMR analysis. One new water-soluble non-starch polysaccharide (PTS-A with the yield of 0.41%) from T. sinense was purified and identified on structural characteristics for the first time. The characterizations of PTS-A were studied on physicochemical properties, main components of monosaccharide (s) and molecular structure. PTS-A was identified as glucan, only containing D-glucoses with the molecular structure of [→6) α-D-Glcp (1→6) α-D-Glcp (1→]n by methylation analysis and NMR. In the determination of total reducing capacity, their reducing abilities could be listed as vitamin C> PTS-A> crude polysaccharides-3> crude polysaccharides-2> crude polysaccharides-1. All of PTS-A, crude polysaccharides-2 and -3 were relatively good scavenger for 1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1- (2,4,6-trinitrophenyl) hydrazyl radicals with the IC50 of 2.81, 4.17 and 3.44 mg/mL, respectively. Thus, the separation and purification of polysaccharides were significant to increase the antioxidant activity in some degree. One new water-soluble 1,6-α-ᴅ-dextran was discovered with the polysaccharide structure identified for the first time. Both PTS-A and crude extracts of polysaccharide performed a potent potential on antioxidant activities. The bioactivities of PTS-A should be generalized to the broader pharmacological effects.

14.
Vet Microbiol ; 247: 108793, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32768236

RESUMO

Porcine epidemic diarrhea virus (PEDV) belongs to the Alphacoronavirus genus in the Coronaviridae family. Similar to other coronaviruses, PEDV encodes two papain-like proteases. Papain-like protease (PLP)2 has been proposed to play a key role in antagonizing host innate immunity. However, the function of PLP1 remains unclear. In this study, we found that overexpression of PLP1 significantly promoted PEDV replication and inhibited production of interferon-ß. Immunoprecipitation and mass spectrometry were used to identify cellular interaction partners of PLP1. Host cell poly(C) binding protein 2 (PCBP2) was determined to bind and interact with PLP1. Both endogenous and overexpressed PCBP2 co-localized with PLP1 in the cytoplasm. Overexpression of PLP1 upregulated expression of PCBP2. Furthermore, overexpression of PCBP2 promoted PEDV replication. Silencing of endogenous PCBP2 using small interfering RNAs attenuated PEDV replication. Taken together, these data demonstrated that PLP1 negatively regulated the production of type 1 interferon by interacting with PCBP2 and promoted PEDV replication.


Assuntos
Papaína/metabolismo , Vírus da Diarreia Epidêmica Suína/metabolismo , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/fisiologia , Animais , Chlorocebus aethiops , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Células HEK293 , Humanos , Interferon beta/genética , Interferon beta/metabolismo , Proteína Proteolipídica de Mielina/metabolismo , Papaína/genética , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/fisiologia , Interferência de RNA , Proteínas de Ligação a RNA , Fator de Necrose Tumoral alfa/farmacologia , Células Vero , Proteínas não Estruturais Virais/genética
15.
Cardiovasc Ther ; 2020: 1230513, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821283

RESUMO

Background: As a multifaceted disease, atherosclerosis is often characterized by the formation and accumulation of plaque anchored to the inner wall of the arteries and causes some cardiovascular diseases and vascular embolism. Numerous studies have reported on the pathogenesis of atherosclerosis. However, fewer studies focused on both genes and immune cells, and the correlation of genes and immune cells was evaluated via comprehensive bioinformatics analyses. Methods: 29 samples of atherosclerosis-related gene expression profiling, including 16 human advanced atherosclerosis plaque (AA) and 13 human early atherosclerosis plaque (EA) samples from the Gene Expression Omnibus (GEO) database, were analyzed to get differentially expressed genes (DEGs) and the construction of protein and protein interaction (PPI) networks. Besides, we detected the relative fraction of 22 immune cell types in atherosclerosis by using the deconvolution algorithm of "cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)." Ultimately, based on the significantly changed types of immune cells, we executed the correlation analysis between DEGs and immune cells to discover the potential genes and pathways associated with immune cells. Results: We identified 17 module genes and 6 types of significantly changed immune cells. Correlation analysis showed that the relative percentage of T cell CD8 has negative correlation with the C1QB expression (R = -0.63, p = 0.02), and the relative percentage of macrophage M2 has positive correlation with the CD86 expression (R = 0.57, p = 0.041) in EA. Meanwhile, four gene expressions (CD53, C1QC, NCF2, and ITGAM) have a high correlation with the percentages of T cell CD8 and macrophages (M0 and M2) in AA samples. Conclusions: In this study, we suggested that the progression of atherosclerosis might be related to CD86, C1QB, CD53, C1QC, NCF2, and ITGAM and that it plays a role in regulating immune-competent cells such as T cell CD8 and macrophages M0 and M2. These results will enable studies of the potential genes associated with immune cells in the progression of atherosclerosis, as well as provide insight for discovering new treatments and drugs.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/imunologia , Biologia Computacional , Perfilação da Expressão Gênica , Macrófagos/imunologia , Placa Aterosclerótica , Transcriptoma , Antígeno B7-2/genética , Antígeno CD11b/genética , Doenças das Artérias Carótidas/diagnóstico por imagem , Proteínas de Transporte/genética , Bases de Dados Genéticas , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Proteínas Mitocondriais/genética , NADPH Oxidases/genética , Fenótipo , Mapas de Interação de Proteínas , Tetraspanina 25/genética
16.
Biosci Microbiota Food Health ; 39(3): 109-116, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32775128

RESUMO

Autism spectrum disorders (ASDs) are prevalent neurobiological conditions with complicated causes worldwide. Increasing researcher awareness of ASD and accumulated evidence suggest that the development of ASD may be strongly linked to the dysbiosis of the gut microbiota. In addition, most of the current studies have compared autistic children and neurotypical children or have compared ASD patients before and after antibiotic treatment. Treatment of autism with traditional Chinese medicine (TCM) has increasingly been promoted, but the relationship between its efficacy and intestinal flora has rarely been reported. Under the premise that treatment with the TCM BuYang HuanWu Tang is effective, we conducted a comparative bioinformatics analysis to identify the overall changes in gut microbiota in relation to ASD by comparing the intestinal flora before and after treatment with TCM and contrasting the intestinal flora with that of healthy controls. At the phylum level, Proteobacteria showed a significant increase in children with ASD, which may be a signature of dysbiosis in the gut microbiota. At the genus level, Blautia, Coprococcus 1, the Lachnospiraceae family, and the Ruminococcaceae family were found at the lowest levels of relative abundance in children with ASD, whereas the abundances of Escherichia-Shigella, Klebsiella, and Flavonifractor were significantly increased compared with those in the healthy control group. In sum, this study characterized the alterations of the intestinal microbiome in children with ASD and its normalization after TCM treatment (TCMT), which may provide novel insights into the diagnosis and therapy of ASD.

17.
Clin Sci (Lond) ; 134(17): 2419-2434, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32812634

RESUMO

BACKGROUND: Retinal endothelial cell (REC) dysfunction induced by diabetes mellitus (DM) is an important pathological step of diabetic retinopathy (DR). Long noncoding RNAs (lncRNAs) have emerged as novel modulators in DR. The present study aimed to investigate the role and mechanism of lncRNA Hotair in regulating DM-induced REC dysfunction. METHODS: The retinal vascular preparations and immunohistochemical staining assays were conducted to assess the role of Hotair in retinal vessel impairment in vivo. The EdU, transwell, cell permeability, CHIP, luciferase activity, RIP, RNA pull-down, and Co-IP assays were employed to investigate the underlying mechanism of Hotair-mediated REC dysfunction in vitro. RESULTS: Hotair expression was significantly increased in diabetic retinas and high glucose (HG)-stimulated REC. Hotair knockdown inhibited the proliferation, invasion, migration, and permeability of HG-stimulated REC in vitro and reduced the retinal acellular capillaries and vascular leakage in vivo. Mechanistically, Hotair bound to LSD1 to inhibit VE-cadherin transcription by reducing the H3K4me3 level on its promoter and to facilitate transcription factor HIF1α-mediated transcriptional activation of VEGFA. Furthermore, LSD1 mediated the effects of Hotair on REC function under HG condition. CONCLUSION: The Hotair exerts its role in DR by binding to LSD1, decreasing VE-cadherin transcription, and increasing VEGFA transcription, leading to REC dysfunction. These findings revealed that Hotair is a potential therapeutic target of DR.

18.
Nat Genet ; 52(8): 811-818, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32632335

RESUMO

We developed cis-X, a computational method for discovering regulatory noncoding variants in cancer by integrating whole-genome and transcriptome sequencing data from a single cancer sample. cis-X first finds aberrantly cis-activated genes that exhibit allele-specific expression accompanied by an elevated outlier expression. It then searches for causal noncoding variants that may introduce aberrant transcription factor binding motifs or enhancer hijacking by structural variations. Analysis of 13 T-lineage acute lymphoblastic leukemias identified a recurrent intronic variant predicted to cis-activate the TAL1 oncogene, a finding validated in vivo by chromatin immunoprecipitation sequencing of a patient-derived xenograft. Candidate oncogenes include the prolactin receptor PRLR activated by a focal deletion that removes a CTCF-insulated neighborhood boundary. cis-X may be applied to pediatric and adult solid tumors that are aneuploid and heterogeneous. In contrast to existing approaches, which require large sample cohorts, cis-X enables the discovery of regulatory noncoding variants in individual cancer genomes.


Assuntos
Elementos Facilitadores Genéticos/genética , Variação Genética/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , RNA não Traduzido/genética , Adolescente , Alelos , Criança , Pré-Escolar , Cromatina/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Oncogenes/genética , Transcrição Genética/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-32632992

RESUMO

Electrochemical sensing based on conventional rigid electrodes has great restrictions for characterizing biomolecules in deformed cells or soft tissues. The recent emergence of stretchable sensors allows electrodes to conformally contact to curved surfaces and perfectly comply with the deformation of living cells and tissues. This provides a powerful strategy to monitor biomolecules from mechanically deformed cells, tissues, and organisms in real time, and opens up new opportunities to explore the mechanotransduction process. In this minireview, we first summarize the fabrication of stretchable electrodes with emphasis on the nanomaterial-enabled strategies. We then describe representative applications of stretchable sensors in the real-time monitoring of mechanically sensitive cells and tissues. Finally, we present the future possibilities and challenges of stretchable electrochemical sensing in cell, tissue, and in vivo detection.

20.
Biomed Res Int ; 2020: 8072639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626765

RESUMO

Background: Breast cancer is the common malignancy with high morbidity and mortality in women. S-phase kinase-associated protein 2 (Skp2) has been characterized to play an oncogenic role in the breast carcinogenesis and progression. Therefore, inactivation of Skp2 in breast cancer might be a novel approach for fighting breast malignancy. A natural compound diosgenin has been reported to exert anticancer activity in a variety of human cancers. However, the underlying mechanism has not been fully determined. Methods: In this study, we aim to explore whether diosgenin performed antitumor activity via inhibition of Skp2 in breast cancer cells using several methods including MTT, Transwell invasion assay, RT-PCR, western blotting, and transfection. Results: We found that diosgenin inhibited cell viability and stimulated apoptosis. Moreover, we found that diosgenin reduced cell invasion in breast cancer cells. Furthermore, diosgenin inhibited the expression of Skp2 in breast cancer cells. Notably, diosgenin reduced cell viability and motility and induced apoptosis via suppression of Skp2 in breast cancer cells. Conclusion: Our findings revealed that diosgenin could be a potential inhibitor of Skp2 for treating breast cancer.

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