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1.
Small ; 20(21): e2308430, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38126626

RESUMO

Graphene nanoribbons (GNRs) are promising in nanoelectronics for their quasi-1D structures with tunable bandgaps. The methods for controllable fabrication of high-quality GNRs are still limited. Here a way to generate sub-5-nm GNRs by annealing single-walled carbon nanotubes (SWCNTs) on Cu(111) is demonstrated. The structural evolution process is characterized by low-temperature scanning tunneling microscopy. Substrate-dependent measurements on Au(111) and Ru(0001) reveal that the intermediate strong SWCNT-surface interaction plays a pivotal role in the formation of GNRs.

2.
Brief Bioinform ; 23(2)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35189638

RESUMO

Identifying genome-wide binding events between circular RNAs (circRNAs) and RNA-binding proteins (RBPs) can greatly facilitate our understanding of functional mechanisms within circRNAs. Thanks to the development of cross-linked immunoprecipitation sequencing technology, large amounts of genome-wide circRNA binding event data have accumulated, providing opportunities for designing high-performance computational models to discriminate RBP interaction sites and thus to interpret the biological significance of circRNAs. Unfortunately, there are still no computational models sufficiently flexible to accommodate circRNAs from different data scales and with various degrees of feature representation. Here, we present HCRNet, a novel end-to-end framework for identification of circRNA-RBP binding events. To capture the hierarchical relationships, the multi-source biological information is fused to represent circRNAs, including various natural language sequence features. Furthermore, a deep temporal convolutional network incorporating global expectation pooling was developed to exploit the latent nucleotide dependencies in an exhaustive manner. We benchmarked HCRNet on 37 circRNA datasets and 31 linear RNA datasets to demonstrate the effectiveness of our proposed method. To evaluate further the model's robustness, we performed HCRNet on a full-length dataset containing 740 circRNAs. Results indicate that HCRNet generally outperforms existing methods. In addition, motif analyses were conducted to exhibit the interpretability of HCRNet on circRNAs. All supporting source code and data can be downloaded from https://github.com/yangyn533/HCRNet and https://doi.org/10.6084/m9.figshare.16943722.v1. And the web server of HCRNet is publicly accessible at http://39.104.118.143:5001/.


Assuntos
Sequenciamento de Cromatina por Imunoprecipitação , RNA Circular , Sítios de Ligação , RNA/genética , RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
3.
BMC Biol ; 21(1): 141, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37337183

RESUMO

BACKGROUND: The harlequin ladybird Harmonia axyridis (Coleoptera: Coccinellidae), native to Asia, has been introduced to other major continents where it has caused serious negative impacts on local biodiversity. Though notable advances to understand its invasion success have been made during the past decade, especially with then newer molecular tools, the conclusions reached remain to be confirmed with more advanced genomic analyses and especially using more samples from larger geographical regions across the native range. Furthermore, although H. axyridis is one of the best studied invasive insect species with respect to life history traits (often comparing invasive and native populations), the traits responsible for its colonization success in non-native areas warrant more research. RESULTS: Our analyses of genome-wide nuclear population structure indicated that an eastern Chinese population could be the source of all non-native populations and revealed several putatively adaptive candidate genomic loci involved in body color variation, visual perception, and hemolymph synthesis. Our estimates of evolutionary history indicate (1) asymmetric migration with varying population sizes across its native and non-native range, (2) a recent admixture between eastern Chinese and American populations in Europe, (3) signatures of a large progressive, historical bottleneck in the common ancestors of both populations and smaller effective sizes of the non-native population, and (4) the southwest origin and subsequent dispersal routes within its native range in China. In addition, we found that while two mitochondrial haplotypes-Hap1 and Hap2 were dominant in the native range, Hap1 was the only dominant haplotype in the non-native range. Our laboratory observations in both China and USA found statistical yet slight differences between Hap1 and Hap2 in some of life history traits. CONCLUSIONS: Our study on H. axyridis provides new insights into its invasion processes into other major continents from its native Asian range, reconstructs a geographic range evolution across its native region China, and tentatively suggests that its invasiveness may differ between mitochondrial haplotypes.


Assuntos
Besouros , Animais , Besouros/genética , Haplótipos , Fenótipo , Genômica , Variação Biológica da População
4.
Sensors (Basel) ; 24(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38475088

RESUMO

A computational spectrometer is a novel form of spectrometer powerful for portable in situ applications. In the encoding part of the computational spectrometer, filters with highly non-correlated properties are requisite for compressed sensing, which poses severe challenges for optical design and fabrication. In the reconstruction part of the computational spectrometer, conventional iterative reconstruction algorithms are featured with limited efficiency and accuracy, which hinders their application for real-time in situ measurements. This study proposes a neural network computational spectrometer trained by a small dataset with high-correlation optical filters. We aim to change the paradigm by which the accuracy of neural network computational spectrometers depends heavily on the amount of training data and the non-correlation property of optical filters. First, we propose a presumption about a distribution law for the common large training dataset, in which a unique widespread distribution law is shown when calculating the spectrum correlation. Based on that, we extract the original dataset according to the distribution probability and form a small training dataset. Then a fully connected neural network architecture is constructed to perform the reconstruction. After that, a group of thin film filters are introduced to work as the encoding layer. Then the neural network is trained by a small dataset under high-correlation filters and applied in simulation. Finally, the experiment is carried out and the result indicates that the neural network enabled by a small training dataset has performed very well with the thin film filters. This study may provide a reference for computational spectrometers based on high-correlation optical filters.

5.
Opt Express ; 31(14): 23325-23349, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37475419

RESUMO

A neural network (NN) computational spectrometer has high reconstruction accuracy and a fast operation speed; however, this type of spectrometer also occupies a large amount of storage in an embedded system due to the excessive computation volume. Contrarily, conventional algorithms such as gradient projection for sparse reconstruction (GPSR) take up less storage, but their spectral reconstruction accuracy is much lower than that of an NN. The major reason is that the performance of a GPSR depends greatly on the non-correlation property of optical filters which may pose challenges for optical filters design and fabrication. In this study, a GPSR algorithm, known as NN-GPSR, is applied to achieve high-precision spectral reconstruction enabled by NN-learned highly correlated filters. A group of NN-learned filters shows high-correlation work as the encoder, and an optimized GPSR algorithm works as the decoder. In this case, large computation volume is exempt and prior knowledge of tens of thousands of images are exploited to get appropriate optical filters design. The experiment data indicate that the NN-GPSR performs well in the reconstructing spectrum and requires far less storage.

6.
Neurochem Res ; 48(5): 1334-1346, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36449198

RESUMO

Background Transplantation of extracellular vesicles (EVs) from stem cells is a feasible scheme for traumatic spinal cord injury (SCI). However, there is no relevant report about stem cells derived EVs loaded with curcumin for SCI treatment. Methods Mouse umbilical cord mesenchymal stem cells (MUMSCs) were incubated in the medium containing curcumin (20 µM) for 48 h. Extracellular vesicles (EVs) and curcumin-primed EVs (Cur-EVs) were collected by ultracentrifugation. Characterizations of EVs/Cur-EVs were analyzed by western blotting with CD9 and CD81 antibodies, transmission electron microscopy and nano-tracking analysis. Curcumin in the Cur-EVs was analyzed by high performance liquid phase chromatography at 430 nm wavelength. Immunofluorescence and in vivo imaging methods were used to confirm biocompatibility of EVs/Cur-EVs in vitro and in vivo. Mice with complete SCI were treated with EVs/Cur-EVs to compare the differences of locomotor function, inflammation, histological changes and remyelination. Results The isolated EVs and Cur-EVs from MUMSCs have good biocompatibility. Compared with the model mice, the locomotor function, inflammation and axonal regeneration of mice were significantly improved after injection of Cur-EVs/EVs. Furthermore, it is more effective for structural and functional recovery of complete SCI after the Cur-EVs treatment compared with the EVs treatment. In the lesioned regions, the macrophage polarization from M1 to M2 phenotype and axonal regeneration were significantly improved in the Cur-EVs group compared with the EVs group. Conclusions Our data suggested that EVs from MUMSCs might be a promising drug delivery vehicle of curcumin for the efficient and biocompatible treatment of severe SCI.


Assuntos
Curcumina , Vesículas Extracelulares , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Ratos , Camundongos , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Cordão Umbilical , Medula Espinal/patologia
7.
PLoS Comput Biol ; 18(12): e1010779, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36520922

RESUMO

Enhancers are short non-coding DNA sequences outside of the target promoter regions that can be bound by specific proteins to increase a gene's transcriptional activity, which has a crucial role in the spatiotemporal and quantitative regulation of gene expression. However, enhancers do not have a specific sequence motifs or structures, and their scattered distribution in the genome makes the identification of enhancers from human cell lines particularly challenging. Here we present a novel, stacked multivariate fusion framework called SMFM, which enables a comprehensive identification and analysis of enhancers from regulatory DNA sequences as well as their interpretation. Specifically, to characterize the hierarchical relationships of enhancer sequences, multi-source biological information and dynamic semantic information are fused to represent regulatory DNA enhancer sequences. Then, we implement a deep learning-based sequence network to learn the feature representation of the enhancer sequences comprehensively and to extract the implicit relationships in the dynamic semantic information. Ultimately, an ensemble machine learning classifier is trained based on the refined multi-source features and dynamic implicit relations obtained from the deep learning-based sequence network. Benchmarking experiments demonstrated that SMFM significantly outperforms other existing methods using several evaluation metrics. In addition, an independent test set was used to validate the generalization performance of SMFM by comparing it to other state-of-the-art enhancer identification methods. Moreover, we performed motif analysis based on the contribution scores of different bases of enhancer sequences to the final identification results. Besides, we conducted interpretability analysis of the identified enhancer sequences based on attention weights of EnhancerBERT, a fine-tuned BERT model that provides new insights into exploring the gene semantic information likely to underlie the discovered enhancers in an interpretable manner. Finally, in a human placenta study with 4,562 active distal gene regulatory enhancers, SMFM successfully exposed tissue-related placental development and the differential mechanism, demonstrating the generalizability and stability of our proposed framework.


Assuntos
Elementos Facilitadores Genéticos , Placenta , Feminino , Humanos , Gravidez , Elementos Facilitadores Genéticos/genética , DNA/genética , Regulação da Expressão Gênica , Linhagem Celular
8.
Nanotechnology ; 35(3)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37905427

RESUMO

Aim. The potential of olfactory ensheathing cells (OECs) as a cell therapy for spinal cord reconstruction and regeneration after injury has drawn significant attention in recent years. This study attempted to investigate the influences of nano-fibrous scaffolds on the growth status and functional properties of OECs.Methods.The ultra-morphology of the scaffolds was visualized using scanning electron microscopy (SEM). To culture OECs, donated cells were subcultured and identified with p75. Cell proliferation, apoptosis, and survival rates were measured through MTT assay, Annexin-V/PI staining, and p75 cell counting, respectively. The adhesion of cells cultured on scaffolds was observed using SEM. Additionally, the functions of OECs cultured on scaffolds were assessed by testing gene expression levels through real time polymerase chain reaction.Results.The electrospun type I collagen-based nano-fibers exhibited a smooth surface and uniform distribution. It was indicated that the proliferation and survival rates of OECs cultured on both randomly oriented and aligned type I collagen-based nano-fibrous scaffolds were higher than those observed in the collagen-coated control. Conversely, apoptosis rates were lower in cells cultured on scaffolds. Furthermore, OEC adhesion was better on the scaffolds than on the control. The expression levels of target genes were significantly elevated in cells cultured on scaffolds versus the controls.Conclusion.As a whole, the utilization of aligned collagen nanofibers has demonstrated significant advantages in promoting cell growth and improving cell function. These findings have important implications for the field of regenerative medicine and suggest that the approach may hold promise for the future therapeutic applications.


Assuntos
Nanofibras , Alicerces Teciduais , Colágeno Tipo I/genética , Células Cultivadas , Colágeno
9.
J Pept Sci ; 29(6): e3469, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36525306

RESUMO

Protein phosphatase-1 (PP1) is a ubiquitous enzyme involved in multiple processes inside cells. PP1-disrupting peptides (PDPs) are chemical tools that selectively bind to PP1 and release its activity. To restrict the activity of PDPs to a cellular compartment, we developed PDP-Mem, a cell membrane-targeting PDP. The membrane localization was achieved through the introduction of a palmitoylated lysine. PDP-Mem was shown to activate PP1α in vitro and to localize to the membrane of HeLa Kyoto and U2OS cells. However, in cells, the combination of the polybasic sequence for cell penetration and the membrane targeting palmitoylated lysine activates the MAPK signaling pathway and induces cytoplasmic calcium release independently of PP1 activation. Therefore, when targeting peptides to cellular membranes, undesired effects induced by the targeting sequence and lipid modification need to be considered.


Assuntos
Lisina , Peptídeos , Humanos , Proteína Fosfatase 1/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo , Células HeLa , Transdução de Sinais , Fosforilação
10.
Molecules ; 29(1)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38202649

RESUMO

Binary ethosome vesicles have been developed as flexible lipid vesicles for the enhanced physicochemical stability and skin delivery of drugs. This work aimed to prepare phloretin-loaded propylene glycol ethosomes (PHL-PGEs) to improve their stability, skin permeability and antioxidant activity. PHL-PGEs were prepared via the ethanol injection method and optimized using different weight ratios of ethanol to propylene glycol (PG). When the ethanol/PG mass ratio changed from 10:0 to 0:10, the encapsulation efficiency and stability of ethosomes increased. At a PHL concentration of 1mg/mL, the EE% was 89.42 ± 2.42 and the DL% was 4.21 ± 0.04, which exhibited their highest values. The encapsulation of the PHL in the PHL-PGEs was strengthened via XRD analysis and FTIR analysis. The results of the in vitro percutaneous permeability test demonstrated that the combined use of ethanol and PG exhibited a notable enhancement in skin permeability, and the skin retention of PHL-PGEs was 1.06 times that of PHL-ethosomes (PHL-Es) and 2.24 times that of the PHL solution. An in vitro antioxidant activity study indicated that solubility and antioxidant activity was potentiated via the nanoencapsulation of phloretin. Therefore, these results confirm the potential of this nanocarrier to enhance physicochemical stability, skin permeability and antioxidant activity.


Assuntos
Antioxidantes , Etanol , Antioxidantes/farmacologia , Permeabilidade , Floretina/farmacologia , Propilenoglicol
11.
J Clin Biochem Nutr ; 73(2): 161-171, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37700848

RESUMO

Metabolic differences between colorectal cancer (CRC) and NI (NI) play an important role in early diagnoses and in-time treatments. We investigated the metabolic alterations between CRC patients and NI, and identified some potential biomarkers, and these biomarkers might be used as indicators for diagnosis of CRC. In this study, there were 79 NI, 50 CRC I patients, 52 CRC II patients, 56 CRC III patients, and 52 CRC IV patients. MS-MS was used to measure the metabolic alterations. Univariate and multivariate data analysis and metabolic pathway analysis were applied to analyze metabolic data and determine differential metabolites. These indicators revealed that amino acid and fatty acids could separate these groups. Several metabolites indicated an excellent variables capability in the separation of CRC patients and NI. Ornithine, arginine, octadecanoyl carnitine, palmitoyl carnitine, adipoyl carnitine, and butyryl carnitine/propanoyl carnitine were selected to distinguish the CRC patients and NI. And methionine and propanoyl carnitine, were directly linked to different stages of CRC. Receiver operating characteristics curves and variables importance in projection both represented an excellent performance of these metabolites. In conclusion, we assessed the difference between CRC patients and NI, which supports guidelines for an early diagnosis and effective treatment.

12.
Opt Express ; 30(8): 13616-13629, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35472971

RESUMO

An all-silicon long-wavelength infrared (LWIR) achromatic metalens based on deep silicon etching is designed in this paper. With a fixed aperture size, the value range of the equivalent optical thickness of the non-dispersive meta-atoms constructing the achromatic metalens determines the minimum f-number. The fabrication characteristic with high aspect ratio of deep silicon etching amplifies the difference value of optical thickness between different meta-atoms by increasing the propagation distance of the propagation mode, which ensures a small f-number to obtain a better imaging resolution. A 280-µm-diameter silicon achromatic metalens with a f-number of 1 and the average focusing efficiency of 27.66% has been designed and simulated to validate the feasibility of this strategy. The simulation results show that the maximum focal length deviation percentage from the target value between the wavelength of 8.6 and 11.4 µm is 1.61%. This achromatic metalens design is expected to play a role in the field of LWIR integrated optical system.

13.
Sensors (Basel) ; 22(13)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35808267

RESUMO

The stray-light suppression of a large off-axis three-mirror anastigmatic space camera has been a hot topic, and this study proposes a composite stray-light suppression strategy that effectively suppresses stray light using the combination of a baffle, retaining ring, and internal antistray light measures. Additionally, the light barrier of the third mirror with a three-layered structure was designed to further optimize the composite stray-light suppression system. At the stray-light simulation analysis stage, in view of the limitations of the Torrance-Sparrow scattering analysis model, an analysis model with wide adaptability is proposed, which can be applied to the stray-light simulation analysis of large-size mirrors with rough surfaces. The simulation results indicate that the point source transmittance of the composite stray-light suppression strategy proposed in this paper is of the order of 10-5 before installing the light barrier of the third mirror, and the veiling glare index of the full field of view is less than 5.8%. After installing the light barrier of the third mirror, the point source transmittance reached the order of 10-8, and the veiling glare index of the full field of view was less than 1.31%. Moreover, the influence of the light barrier of the third mirror on the modulation transfer function of the system was less than 2.3%. The modulation transfer function test of the large-width off-axis three-mirror anastigmatic space camera in a simulated vacuum on-orbit environment was completed, and the test results indicated that the negative impact of the light barrier of the third mirror on the modulation transfer function was less than 3.6%. Moreover, an out-of-field imaging test of the space camera was conducted and the results showed that the image was clear, and the SNR reached 80 dB. The simulation and experimental results prove that the solution in this study can effectively solve the problem of stray-light suppression for large off-axis three-mirror anastigmatic space cameras.

14.
BMC Cancer ; 21(1): 1345, 2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34922489

RESUMO

BACKGROUNDS: Osteosarcomas are one of the most common primary malignant tumors of bone. It primarily occurs in children and adolescents, with the second highest incidence among people over 50 years old. Although there were immense improvements in the survival of patients with osteosarcoma in the past 30 years, targetable mutations and agents of osteosarcomas still have been generally not satisfactory. Therefore, it is of great importance to further explore the highly specialized immune environment of bone, genes related to macrophage infiltration and potential therapeutic biomarkers and targets. METHODS: The 11 expression data sets of OS tissues and the 11 data sets of adjacent non-tumorous tissues available in the GEO database GSE126209 were used to conduct immune infiltration analysis. Then, through WGCNA analysis, we acquired the co-expression modules related to Mast cells activated and performed the GO and KEGG enrichment analysis. Next, we did the survival prognosis analysis and plotted a survival curve. Finally, we analyzed the COX multivariate regression of gene expression on clinical parameters and drew forest maps for visualization by the forest plot package. RESULTS: OS disease-related immune cell populations, mainly Mast cells activated, have higher cell content (p = 0.006) than the normal group. Then, we identified co-expression modules related to Mast cells activated. In sum, a total of 822 genes from the top three strongest positive correlation module MEbrown4, MEdarkslateblue and MEnavajowhite2 and the strongest negative correlation module MEdarkturquoise. From that, we identified nine genes with different levels in immune cell infiltration related to osteosarcoma, eight of which including SORBS2, BAIAP2L2, ATAD2, CYGB, PAMR1, PSIP1, SNAPC3 and ZDHHC21 in their low abundance have higher disease-free survival probability than the group in their high abundances. CONCLUSION: These results could assist clinicians to select targets for immunotherapies and individualize treatment strategies for patients with OS.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Recidiva Local de Neoplasia/epidemiologia , Osteossarcoma/imunologia , Adolescente , Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Perfilação da Expressão Gênica , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Mastócitos/imunologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/mortalidade , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
15.
Bioorg Med Chem Lett ; 33: 127738, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33316404

RESUMO

Through structural modification of an oxalamide derived chemotype, a novel class of highly potent, orally bioavailable IDO1-specific inhibitors was identified. Representative compound 18 inhibited human IDO1 with IC50 values of 3.9 nM and 52 nM in a cellular and human whole blood assay, respectively. In vitro assessment of the ADME properties of 18 demonstrated very high metabolic stability. Pharmacokinetic profiling in mice showed a significantly reduced clearance compared to the oxalamides. In a mouse pharmacodynamic model 18 nearly completely suppressed lipopolysaccharide-induced kynurenine production. Hepatocyte data of 18 suggest the human clearance to be in a similar range to linrodostat (1).


Assuntos
Amidas/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Ácido Oxâmico/farmacologia , Amidas/síntese química , Amidas/química , Animais , Compostos Bicíclicos com Pontes/síntese química , Compostos Bicíclicos com Pontes/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cinurenina/antagonistas & inibidores , Cinurenina/biossíntese , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Ácido Oxâmico/síntese química , Ácido Oxâmico/química , Relação Estrutura-Atividade
16.
J Org Chem ; 85(3): 1712-1717, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31841001

RESUMO

We describe here the development of a photoreleasable version of a protein phosphatase-1 (PP1)-disrupting peptide (PDP-Nal) that triggers protein phosphatase-1 activity. PDP-Nal is a 23 mer that binds to PP1 through several interactions. It was photocaged on a tyrosine residue, which required the exchange of phenylalanine in PDP-Nal to tyrosine in order to disrupt the most important binding interface. This PDP-caged can be light-controlled in live cells.


Assuntos
Peptídeos , Proteína Fosfatase 1
17.
J Mater Sci Mater Med ; 31(5): 48, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32405818

RESUMO

BACKGROUND: Skin injury is a kind of common tissue damage in daily life and war. Silk fibroin (SF) is becoming an engineered material for skin wound repair due to its superior unique physical and chemical properties. The present study aimed to illustrate mechanism of SF hydrogel promoting skin repair in the second degree burn mice. METHODS: Heat shock models were established. In vitro, cells were culture for 50 min at 44 °C water bath; while in vivo, the skin of anesthetic mice were treat with soldering iron at 90 °C. Then, they divided into silk fibroin gel group, purilon gel group and control (blank) group. The cellular activity of proliferation and apoptosis was detected by Kit-8, flow cytometry and HE-staining, and the migration and adhesion were detected by scratch test. qRT-PCR and WB were employed to detected adhesion and migration related genes and proteins expression. TLN1 siRNA and overexpression technologies were also employed to illustrate the potential mechanism of SF effects. RESULTS: Compared with the purilon gel group and control group, SF hydrogel could enhance cell proliferation, migration and adhesion and increase the expression of adhesion and migration related proteins (P < 0.05), which promote burn wound healing. CONCLUSIONS: Through the inhibition, overexpression and rescue experiments of Talin1, we proved that silk fibroin hydrogel promote burn wound healing through regulating TLN1 expression and affecting cell adhesion and migration.


Assuntos
Queimaduras/terapia , Fibroínas/química , Hidrogéis/química , Animais , Apoptose/efeitos dos fármacos , Adesão Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Células Endoteliais , Fibroblastos , Humanos , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Interferência de RNA , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Propriedades de Superfície , Talina/genética , Talina/metabolismo
18.
Chembiochem ; 20(1): 66-71, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30338897

RESUMO

Protein phosphatase-1 (PP1)-disrupting peptides (PDPs) are selective chemical modulators of PP1 that liberate the active PP1 catalytic subunit from regulatory proteins; thus allowing the dephosphorylation of nearby substrates. We have optimized the original cell-active PDP3 for enhanced stability, and obtained insights into the chemical requirements for stabilizing this 23-mer peptide for cellular applications. The optimized PDP-Nal was used to dissect the involvement of PP1 in the MAPK signaling cascade. Specifically, we have demonstrated that, in human osteosarcoma (U2OS) cells, phosphoMEK1/2 is a direct substrate of PP1, whereas dephosphorylation of phosphoERK1/2 is indirect and likely mediated through enhanced tyrosine phosphatase activity after PDP-mediated PP1 activation. Thus, as liberators of PP1 activity, PDPs represent a valuable tool for identifying the substrates of PP1 and understanding its role in diverse signaling cascades.


Assuntos
Peptídeos/metabolismo , Proteína Fosfatase 1/metabolismo , Sequência de Aminoácidos , Linhagem Celular Tumoral , Histonas/química , Histonas/metabolismo , Humanos , MAP Quinase Quinase 1/química , MAP Quinase Quinase 1/metabolismo , MAP Quinase Quinase Quinase 2/química , MAP Quinase Quinase Quinase 2/metabolismo , Sistema de Sinalização das MAP Quinases , Proteína Quinase 1 Ativada por Mitógeno/química , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/química , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação
19.
Basic Res Cardiol ; 114(2): 13, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30788598

RESUMO

Increased late sodium current (late INa) is an important arrhythmogenic trigger in cardiac disease. It prolongs cardiac action potential and leads to an increased SR Ca2+ leak. This study investigates the contribution of Ca2+/Calmodulin-dependent kinase II (CaMKII), protein kinase A (PKA) and conversely acting protein phosphatases 1 and 2A (PP1, PP2A) to this subcellular crosstalk. Augmentation of late INa (ATX-II) in murine cardiomyocytes led to an increase of diastolic Ca2+ spark frequency and amplitudes of Ca2+ transients but did not affect SR Ca2+ load. Interestingly, inhibition of both, CaMKII and PKA, attenuated the late INa-dependent induction of the SR Ca2+ leak. PKA inhibition additionally reduced the amplitudes of systolic Ca2+ transients. FRET-measurements revealed increased levels of cAMP upon late INa augmentation, which could be prevented by simultaneous inhibition of Na+/Ca2+-exchanger (NCX) suggesting that PKA is activated by Ca2+-dependent cAMP-production. Whereas inhibition of PP2A showed no effect on late INa-dependent alterations of Ca2+ cycling, additional inhibition of PP1 further increased the SR Ca2+ leak. In line with this, selective activation of PP1 yielded a strong reduction of the late INa-induced SR Ca2+ leak and did not affect systolic Ca2+ release. This study indicates that phosphatase/kinase-balance is perturbed upon increased Na+ influx leading to disruption of ventricular Ca2+ cycling via CaMKII- and PKA-dependent pathways. Importantly, an activation of PP1 at RyR2 may represent a promising new toehold to counteract pathologically increased kinase activity.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Miócitos Cardíacos/metabolismo , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 2/metabolismo , Potenciais de Ação/fisiologia , Animais , Cálcio/metabolismo , Camundongos , Sódio/metabolismo
20.
Cancer Cell Int ; 19: 104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31043859

RESUMO

BACKGROUND: Increasing reports demonstrated that dysregulated expression of microRNAs (miRNAs) leads to the progression of various tumors. Previous studies revealed that miR-328-3p exhibited dysregulated expression in various types of tumors. However, its function and underlying mechanism in osteosarcoma (OS) are still unexplored. METHODS: The expression of miR-328-3p in the tissues and OS cell lines was detected by qRT-PCR analysis. The effects of miR-328-3p in the proliferation were analyzed by MTT assay. The proliferation and apoptosis of OS cells were examined by colony formation assay and TUNEL staining respectively. The migration and tumor formation ability of OS cells were measured by wound healing assay and xenograft in vivo mice assay. Furthermore, the regulatory roles of miR-328-3p/MMP16 were determined by western blot and luciferase reporter assay. RESULTS: The expression of miR-328-3p was significantly decreased in OS tissues and cell lines. Furthermore, overexpression of miR-328-3p inhibited the cell proliferation and migration, but promoted the apoptosis of OS cells in vitro. Moreover, the analysis in vivo showed that miR-328-3p effectively suppressed the formation of tumors. According to the results of western blot analysis and luciferase reporter assay, we identified matrix metalloproteinase-16 (MMP-16) acted as a direct target of miR-328-3p. Moreover, the expression level of MMP-16, which participates in the occurrence and development of many cancers, was negatively correlated with the miR-328-3p expression in OS cells. CONCLUSION: miR-328-3p inhibited the proliferation, migration but accelerated the apoptosis of OS by directly inhibiting MMP-16. And miR-328-3p/MMP-16 axis may be one of the mechanisms of OS development and a novel potential method for the treatment of OS in clinic.

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