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1.
Int J Mol Sci ; 22(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34445212

RESUMO

Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs with covalent closed loop structure. Researchers have revealed that circRNAs play an important role in human diseases. As experimental identification of interactions between circRNA and disease is time-consuming and expensive, effective computational methods are an urgent need for predicting potential circRNA-disease associations. In this study, we proposed a novel computational method named GATNNCDA, which combines Graph Attention Network (GAT) and multi-layer neural network (NN) to infer disease-related circRNAs. Specially, GATNNCDA first integrates disease semantic similarity, circRNA functional similarity and the respective Gaussian Interaction Profile (GIP) kernel similarities. The integrated similarities are used as initial node features, and then GAT is applied for further feature extraction in the heterogeneous circRNA-disease graph. Finally, the NN-based classifier is introduced for prediction. The results of fivefold cross validation demonstrated that GATNNCDA achieved an average AUC of 0.9613 and AUPR of 0.9433 on the CircR2Disease dataset, and outperformed other state-of-the-art methods. In addition, case studies on breast cancer and hepatocellular carcinoma showed that 20 and 18 of the top 20 candidates were respectively confirmed in the validation datasets or published literature. Therefore, GATNNCDA is an effective and reliable tool for discovering circRNA-disease associations.


Assuntos
Neoplasias da Mama , Carcinoma Hepatocelular , Biologia Computacional , Bases de Dados de Ácidos Nucleicos , Neoplasias Hepáticas , Redes Neurais de Computação , RNA Circular , RNA Neoplásico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo
2.
PLoS Comput Biol ; 17(7): e1009165, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34252084

RESUMO

miRNAs belong to small non-coding RNAs that are related to a number of complicated biological processes. Considerable studies have suggested that miRNAs are closely associated with many human diseases. In this study, we proposed a computational model based on Similarity Constrained Matrix Factorization for miRNA-Disease Association Prediction (SCMFMDA). In order to effectively combine different disease and miRNA similarity data, we applied similarity network fusion algorithm to obtain integrated disease similarity (composed of disease functional similarity, disease semantic similarity and disease Gaussian interaction profile kernel similarity) and integrated miRNA similarity (composed of miRNA functional similarity, miRNA sequence similarity and miRNA Gaussian interaction profile kernel similarity). In addition, the L2 regularization terms and similarity constraint terms were added to traditional Nonnegative Matrix Factorization algorithm to predict disease-related miRNAs. SCMFMDA achieved AUCs of 0.9675 and 0.9447 based on global Leave-one-out cross validation and five-fold cross validation, respectively. Furthermore, the case studies on two common human diseases were also implemented to demonstrate the prediction accuracy of SCMFMDA. The out of top 50 predicted miRNAs confirmed by experimental reports that indicated SCMFMDA was effective for prediction of relationship between miRNAs and diseases.

3.
Viruses ; 13(6)2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199601

RESUMO

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutating with increasing speed worldwide. Therefore, there is an urgent need for a simple, sensitive, and high-throughput (HTP) assay to quantify virus-host interactions in order to quickly evaluate the infectious ability of mutant viruses and to develop or validate virus-inhibiting drugs. Here, we developed an ultrasensitive bioluminescent biosensor to evaluate virus-cell interactions by quantifying the interaction between the SARS-CoV-2 receptor binding domain (RBD) and its cellular receptor angiotensin-converting enzyme 2 (ACE2) both in living cells and in vitro. We have successfully used this novel biosensor to analyze SARS-CoV-2 RBD mutants and evaluated candidate small molecules (SMs), antibodies, and peptides that may block RBD:ACE2 interaction. This simple, rapid, and HTP biosensor tool will significantly expedite the detection of viral mutants and the anti-COVID-19 drug discovery process.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Técnicas Biossensoriais/métodos , Interações entre Hospedeiro e Microrganismos/fisiologia , Proteínas Luminescentes/metabolismo , SARS-CoV-2/metabolismo , Anticorpos Neutralizantes/imunologia , Sítios de Ligação , Células HEK293 , Ensaios de Triagem em Larga Escala/métodos , Humanos , Técnicas In Vitro , Ligação Proteica , Domínios Proteicos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
Am J Clin Pathol ; 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34302336

RESUMO

OBJECTIVES: Choosing Wisely Canada (CWC) publishes practices that may contribute to medical overuse and patient harm. Many practices concern laboratory testing, but the recommendations are often written for the test-ordering professionals. Our objective was to develop a list for CWC reflecting the scope of practice of nonpathologist medical laboratory professionals (MLPs). METHODS: We used a national survey, a convention session, and a panel of MLPs from across Canada to generate content for the CWC list. We used a modified Delphi process to identify the most important items and scoping reviews to gather evidence supporting each item. RESULTS: We identified 95 potential CWC list items. After 2 Delphi rounds, there was little movement in the top items. Scoping reviews revealed varying degrees of evidentiary support, which influenced the composition of the final list of 7 CWC items submitted. Three of the final recommendations address ways MLPs preserve the status quo with respect to overutilization of laboratory tests by other health care professionals. The remaining recommendations prompt MLPs to exert clinical judgment in specific scenarios, particularly where they can impact blood collection volumes. CONCLUSIONS: This work brings a more nuanced and comprehensive understanding of the relationships among MLPs, patient safety, and resource waste.

5.
BMC Vet Res ; 17(1): 191, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985499

RESUMO

BACKGROUND: Tetratrichomonas gallinarum is parasitic protozoa with a wide host range. However, its lethal infection is rare reported. CASE PRESENTATION: Here, we described the first lethal cases of T. gallinarum infection in black swans in China. Five black swans died within a week in succession without obvious symptoms except mild diarrhea. At necropsy, severe lesions were observed in caeca with thickened caecal walls and hemorrhages in the mucosa. A large number of moving trophozoites were found in the contents of the cecum by microscopic examination. The livers were enlarged with multiple bleeding spots on the surface. Histopathology of the livers showed mononuclear cell infiltration and moderate hyperplasia of fibrous tissue. The histopathology of the cecum showed that the villi of the cecum were edematous. Finally, the presence of T. gallinarum was determined by specific PCR andin-situ hybridization assay. Additionally, common pathogens that can cause similar symptoms were excluded. CONCLUSIONS: The death of the black swan was caused by T. gallinarum, suggesting that the parasite might be a new threat to the Cygnus birds.


Assuntos
Doenças das Aves/parasitologia , Infecções Protozoárias em Animais/patologia , Trichomonadida/isolamento & purificação , Animais , Anseriformes , Doenças das Aves/patologia , Doenças do Ceco/parasitologia , Doenças do Ceco/patologia , China , Hibridização In Situ/veterinária , Fígado/parasitologia , Fígado/patologia , Reação em Cadeia da Polimerase/veterinária , Trichomonadida/genética
6.
BMC Med Inform Decis Mak ; 21(Suppl 1): 133, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33882934

RESUMO

BACKGROUND: MicroRNAs (miRNAs) have been confirmed to have close relationship with various human complex diseases. The identification of disease-related miRNAs provides great insights into the underlying pathogenesis of diseases. However, it is still a big challenge to identify which miRNAs are related to diseases. As experimental methods are in general expensive and time-consuming, it is important to develop efficient computational models to discover potential miRNA-disease associations. METHODS: This study presents a novel prediction method called HFHLMDA, which is based on high-dimensionality features and hypergraph learning, to reveal the association between diseases and miRNAs. Firstly, the miRNA functional similarity and the disease semantic similarity are integrated to form an informative high-dimensionality feature vector. Then, a hypergraph is constructed by the K-Nearest-Neighbor (KNN) method, in which each miRNA-disease pair and its k most relevant neighbors are linked as one hyperedge to represent the complex relationships among miRNA-disease pairs. Finally, the hypergraph learning model is designed to learn the projection matrix which is used to calculate uncertain miRNA-disease association score. RESULT: Compared with four state-of-the-art computational models, HFHLMDA achieved best results of 92.09% and 91.87% in leave-one-out cross validation and fivefold cross validation, respectively. Moreover, in case studies on Esophageal neoplasms, Hepatocellular Carcinoma, Breast Neoplasms, 90%, 98%, and 96% of the top 50 predictions have been manually confirmed by previous experimental studies. CONCLUSION: MiRNAs have complex connections with many human diseases. In this study, we proposed a novel computational model to predict the underlying miRNA-disease associations. All results show that the proposed method is effective for miRNA-disease association predication.


Assuntos
Neoplasias da Mama , Neoplasias Esofágicas , MicroRNAs , Algoritmos , Biologia Computacional , Predisposição Genética para Doença , Humanos , MicroRNAs/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-33735084

RESUMO

MicroRNAs (miRNAs) are a class of non-coding RNAs that play critical role in many biological processes, such as cell growth, development, differentiation and aging. Increasing studies have revealed that miRNAs are closely involved in many humandiseases. Therefore, the prediction of miRNA-disease associations is of great significance to the study of the pathogenesis, diagnosis and intervention of human disease. However, biological experimentally methods are usually expensive in time and money, while computational methods can provide an efficient way to infer the underlying disease-related miRNAs. In this study, we propose a novel method to predict potential miRNA-disease associations, called SVAEMDA. Our method mainly consider the miRNA-disease association prediction as semi-supervised learning problem. SVAEMDA integrates disease semantic similarity, miRNA functional similarity and respective Gaussian interaction profile (GIP) similarities. The integrated similarities are used to learn the representations of diseases and miRNAs. SVAEMDA trains a variational autoencoder based predictor by using known miRNA-disease associations, with the form of concatenated dense vectors. Reconstruction probability of the predictor is used to measure the correlation of the miRNA-disease pairs. Experimental results show that SVAEMDA outperforms other stat-of-the-art methods.

8.
Infect Immun ; 89(5)2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33619031

RESUMO

To investigate the molecular pathogenesis of bone with osteomyelitis, we developed implant-associated osteomyelitis (IAOM) models in mice. An orthopedic stainless pin was surgically placed in the right femoral midshaft of mice, followed by an inoculation of Staphylococcus aureus into the medullary cavity. Typical characteristics of IAOM, like periosteal reaction and intraosseous abscess, occurred by day 14 postinfection. By day 28 postinfection, necrotic abscess, sequestrum formation, and deformity of the whole femur were observed. Transcriptional analysis identified 101 and 1,702 differentially expressed genes (DEGs) between groups by days 3 and 14 postinfection, respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the enrichment of pathways in response to the bacterium, receptor-ligand activity, and chemokine signaling by day 3 postinfection. However, by day 14 postinfection, the enrichment switched to angiogenesis, positive regulation of cell motility and migration, skeletal system development, and cytokine-cytokine receptor interaction. Furthermore, protein-protein interaction network analysis identified 4 cytokines (interleukin 6 [IL-6], Cxcl10, gamma interferon [IFN-γ], and Cxcl9) associated with IAOM at an early stage of infection. Overall, as the pathological changes in this mouse model were consistent with those in human IAOM, our model may be used to investigate the mechanism and treatment of IAOM. Furthermore, the data for transcriptome sequencing and bioinformatic analysis will be an important resource for dissecting the molecular pathogenesis of bone with IAOM.


Assuntos
Osteomielite/etiologia , Infecções Relacionadas à Prótese/genética , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Transcriptoma , Animais , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Biologia Computacional/métodos , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Camundongos
9.
Artigo em Inglês | MEDLINE | ID: mdl-32991287

RESUMO

Numerous studies have shown that microRNAs are associated with the occurrence and development of human diseases. Thus, studying disease-associated miRNAs is significantly valuable to the prevention, diagnosis and treatment of diseases. In this paper, we proposed a novel method based on matrix completion and non-negative matrix factorization (MCNMF) for predicting disease-associated miRNAs. Due to the information inadequacy on miRNA similarities and disease similarities, we calculated the latter via two models, and introduced the Gaussian interaction profile kernel similarity. In addition, the matrix completion (MC) was employed to further replenish the miRNA and disease similarities to improve the prediction performance. And to reduce the sparsity of miRNA-disease association matrix, the method of weighted K nearest neighbor (WKNKN) was used, which is a pre-processing step. We also utilized non-negative matrix factorization (NMF) using dual L2,1-norm, graph Laplacian regularization, and Tikhonov regularization to effectively avoid the overfitting during the prediction. Finally, several experiments and a case study were implemented to evaluate the effectiveness and performance of the proposed MCNMF model. The results indicated that our method could reliably and effectively predict disease-associated miRNAs.

11.
ACS Appl Mater Interfaces ; 12(37): 41819-41831, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32812744

RESUMO

The safety issue caused by thermal runaway poses a huge threat toward the lifespan and application of high-density electrochemical energy storage devices, especially in the field of micro-energy, such as microsupercapacitors (MSCs). The heat accumulation is difficult to be eliminated, considering the narrow space inside integrated electronic devices attached to the MSC group. Active thermal management is of paramount importance to ensure the normal operation of electronic devices. However, existing one-time thermal protection strategies cannot fully meet current requirements. Herein, we report a promising thermoreversible temperature-responsive electrolyte system, which can shut down the current flow before thermal runaway occurs, thanks to the sol-gel transition of Pluronic [poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide)]-based graft copolymer solution. As the temperature rises to 80 °C, the self-protective electrolyte will change from the sol state to gel state. Meanwhile, the internal resistance increases and ionic conductivity decreases gradually as a result of the gelation of the sol electrolyte. The capacity of the energy storage device using the self-protective electrolyte is reduced by about 95%, and the ionic conductivity remains at only 1% at 80 °C compared with the initial value at room temperature, and it can be restored after cooling down. During 20 heating/cooling cycles, the electrochemical performance is substantially stable, demonstrating a potential approach to achieve repeatability and self-protection for micro-energy storage devices according to temperature changes. In addition, we integrated the as-prepared self-protective electrolyte into MSCs via three-dimensional printing technology to design an all-printed transferable micro-energy storage device with the dynamic reversible self-protection behavior, and the thermo-switchable protection mechanism under series and parallel conditions were studied under appropriate temperature window (25-80 °C). The strategy disclosed herein is expected to provide new insights into the new-generation smart MSCs for their wide applications in diverse fields such as microelectronics and wearable devices.

12.
PeerJ ; 8: e9484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742785

RESUMO

Background: Bone marrow adipocyte (BMA), closely associated with bone degeneration, shares common progenitors with osteoblastic lineage. However, the intrinsic mechanism of cells fate commitment between BMA and osteogenic lineage remains unclear. Methods: Gene Expression Omnibus (GEO) dataset GSE107789 publicly available was downloaded and analyzed. Differentially expressed genes (DEGs) were analyzed using GEO2R. Functional and pathway enrichment analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were conducted by The Database for Annotation, Visualization and Integrated Discovery and Gene set enrichment analysis software. Protein-protein interactions (PPI) network was obtained using STRING database, visualized and clustered by Cytoscape software. Transcriptional levels of key genes were verified by real-time quantitative PCR in vitro in Bone marrow stromal cells (BMSCs) undergoing adipogenic differentiation at day 7 and in vivo in ovariectomized mice model. Results: A total of 2,869 DEGs, including 1,357 up-regulated and 1,512 down-regulated ones, were screened out from transcriptional profile of human BMSCs undergoing adipogenic induction at day 7 vs. day 0. Functional and pathway enrichment analysis, combined with modules analysis of PPI network, highlighted ACSL1, sphingosine 1-phosphate receptors 3 (S1PR3), ZBTB16 and glypican 3 as key genes up-regulated at the early stage of BMSCs adipogenic differentiation. Furthermore, up-regulated mRNA expression levels of ACSL1, S1PR3 and ZBTB16 were confirmed both in vitro and in vivo. Conclusion: ACSL1, S1PR3 and ZBTB16 may play crucial roles in early regulation of BMSCs adipogenic differentiation.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32793507

RESUMO

Effective management of infectious osteomyelitis relies on timely microorganism identification and appropriate antibiotic therapy. Extracellular vesicles (EVs) carry protein and genetic information accumulated rapidly in the circulation upon infection. Rat osteomyelitis models infected by Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli were established for the present study. Serum EVs were isolated 3 days after infection. The size and number of serum EVs from infected rats were significantly higher than those from controls. In addition, bacterial aggregation assay showed that the S. aureus and E. coli formed large aggregates in response to the stimulation of serum EVs from S. aureus-infected and E. coli-infected rats, respectively. Treatment of EVs-S. epidermidis led to large aggregates of S. epidermidis and E. coli, whereas stimulation of EVs-P. aeruginosa to large aggregates of S. aureus and P. aeruginosa. To evaluate the changes in EVs in osteomyelitis patients, 28 patients including 5 S. aureus ones and 21 controls were enrolled. Results showed that the size and number of serum EVs from S. aureus osteomyelitis patients were higher than those from controls. Further analysis using receiver operating characteristic curves revealed that only the particle size might be a potential diagnostic marker for osteomyelitis. Strikingly, serum EVs from S. aureus osteomyelitis patients induced significantly stronger aggregation of S. aureus and a cross-reaction with P. aeruginosa. Together, these findings indicate that the size and number of serum EVs may help in the diagnosis of potential infection and that EVs-bacteria aggregation assay may be a quick test to identify infectious microorganisms for osteomyelitis patients.


Assuntos
Vesículas Extracelulares , Osteomielite , Infecções Estafilocócicas , Animais , Biomarcadores , Escherichia coli , Humanos , Osteomielite/diagnóstico , Ratos , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus
14.
Front Microbiol ; 11: 1301, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32595631

RESUMO

Staphylococcus aureus (S. aureus) infection-induced osteomyelitis is a great challenge in clinic treatment. Identification of the essential genes and biological processes that are specifically changed in mononuclear cells at an early stage of S. aureus osteomyelitis is of great clinical significance. Based on transcriptional dataset GSE16129 available publicly, a bioinformatic analysis was performed to identify the differentially expressed genes of osteomyelitis caused by S. aureus infection. ERBB2, TWIST1, and NANOG were screened out as the most valuable osteomyelitis-related genes (OMRGs). A mice model of implant-associated S. aureus osteomyelitis was used to verify the above genes. We found significantly up-regulated expression of TWIST1 in macrophages and accumulation of macrophages around the infected implant. Meanwhile, S. aureus infection increased the expression of TWIST1, MMP9, and MMP13, and stimulated the migration and phagocytosis function of Raw 264.7 cells. Additionally, knock-down of the expression of TWIST1 by siRNA could significantly down-regulate MMP9 and MMP13 and suppress the migration and phagocytosis ability of macrophages in response to S. aureus infection. Furthermore, we found that NF-κB signaling was activated in Raw 264.7 cells by S. aureus and that inhibition of NF-κB signaling by Bay11-7082 blocked the expression of TWIST1, MMP9, and MMP13 as well as cell migration and phagocytosis evoked by S. aureus. Our findings demonstrate that NF-κB/TWIST1 is necessary for migration and phagocytosis of macrophages in response to S. aureus infection. Our study highlights the essential role of NF-κB/TWIST1 in early innate immune response to S. aureus infection in bone.

15.
J Orthop Translat ; 24: 12-22, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32518750

RESUMO

Background: Abnormal bone formation in subchondral bone resulting from uncoupled bone remodeling is considered a central feature in osteoarthritis (OA) pathogenesis. H-type vessels can couple angiogenesis and osteogenesis. We previously revealed that elevated H-type vessels in subchondral bone were correlated with OA and focal adhesion kinase (FAK) in MSCs is critical for H-type vessel formation in osteoporosis. The aim of this study was to explore the correlation between H-type vessels and MSCs in OA pathogenesis through regulation of H-type vessel formation using defactinib (an FAK inhibitor). Methods: In vivo: 3-month-old male C57BL/6J (WT) mice were randomly divided into three groups: sham controls, vehicle-treated ACLT mice, and defactinib-treated ACLT mice (25 mg/kg, intraperitoneally weekly). In vitro: we explored the role of conditioned medium (CM) of MSCs from subchondral bone of different groups on the angiogenesis of endothelial cells (ECs). Flow cytometry, Western blotting, ELISA, real time (RT)-PCR, immunostaining, CT-based microangiography, and bone micro-CT (µCT) were used to detect changes in relative cells and tissues. Results: This study demonstrated that inhibition of H-type vessels with defactinib alleviated OA by inhibiting H-type vessel-linked MSCs in subchondral bone. During OA pathogenesis, H-type vessels and MSCs formed a positive feedback loop contributing to abnormal bone formation in subchondral bone. Elevated H-type vessels provided indispensable MSCs for abnormal bone formation in subchondral bone. Flow cytometry and immunostaining results confirmed that the amount of MSCs in subchondral bone was obviously higher in vehicle-treated ACLT mice than that in sham controls and defactinib-treated ACLT mice. In vitro, p-FAK in MSCs from subchondral bone of vehicle-treated ALCT mice increased significantly relative to other groups. Further, the CM from MSCs of vehicle-treated ACLT mice enhanced angiogenesis of ECs through FAK-Grb2-MAPK-linked VEGF expression. Conclusions: Our results demonstrate that defactinib inhibits OA by suppressing the positive feedback loop between H-type vessels and MSCs in subchondral bone. The translational potential of this article: Our results provide a mechanistic rationale for the use of defactinib as an effective candidate for OA treatment.

16.
Front Genet ; 11: 354, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32351545

RESUMO

Accumulating biological and clinical evidence has confirmed the important associations between microRNAs (miRNAs) and a variety of human diseases. Predicting disease-related miRNAs is beneficial for understanding the molecular mechanisms of pathological conditions at the miRNA level, and facilitating the finding of new biomarkers for prevention, diagnosis and treatment of complex human diseases. However, the challenge for researchers is to establish methods that can effectively combine different datasets and make reliable predictions. In this work, we propose the method of Multi-Similarity based Combinative Hypergraph Learning for Predicting MiRNA-disease Association (MSCHLMDA). To establish this method, complex features were extracted by two measures for each miRNA-disease pair. Then, K-nearest neighbor (KNN) and K-means algorithm were used to construct two different hypergraphs. Finally, results from combinative hypergraph learning were used for predicting miRNA-disease association. In order to evaluate the prediction performance of our method, leave-one-out cross validation and 5-fold cross validation was implemented, showing that our method had significantly improved prediction performance compared to previously used methods. Moreover, three case studies on different human complex diseases were performed, which further demonstrated the predictive performance of MSCHLMDA. It is anticipated that MSCHLMDA would become an excellent complement to the biomedical research field in the future.

17.
Opt Express ; 28(7): 9642-9652, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32225567

RESUMO

Although fruitful investigations of carrier phase estimation (CPE) have been conducted for a traditional coherent fiber optical transmission, there are few studies on the CPE for a nonlinear Fourier transform (NFT) based transmission. A laser linewidth induced phase noise leads to a phase rotation of the nonlinear spectra and the scattering data, which is similar to its effect on the linear spectra. Here, we first identify that both feed forward the M-th power, and the blind phase search (BPS)-based CPE can function well in the nonlinear frequency division multiplexing (NFDM) transmission with discrete spectrum modulation. Then, a performance comparison between two CPE schemes is presented for various modulation formats under the scenario of a single eigenvalue NFDM transmission. Our simulation results indicate that the laser linewidth tolerances of 2 GBaud quadrature phase shift keying (QPSK), 8-phase shift keying (8-PSK), and 16-amplitude phase shift keying (16-APSK) are 2.3 MHz, 1.05 MHz, and 250 KHz, respectively, given a 1-dB optical signal to noise ratio (OSNR) penalty at BER = 10-3. Finally, the BPS algorithm is experimentally verified under the same scenario of a 2 GBaud back-to-back transmission, due to the use of a semiconductor laser with a 100 KHz linewidth.

18.
J Cell Physiol ; 235(11): 8653-8666, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32324278

RESUMO

Osteoarthritis (OA), a disease of the entire joint, is characterized by abnormal bone remodeling and coalescent degradation of articular cartilage. We have previously found that elevated levels of H-type vessels in subchondral bone correlate with OA and that focal adhesion kinase (FAK) is critical for H-type vessel formation in osteoporosis. However, the potential role of FAK in OA remains unexplored. Here, we demonstrate that the p-FAK level was dramatically elevated in subchondral bone following anterior cruciate ligament transection (ACLT) in rats. Specific inhibition of FAK signaling with Y15 in subchondral bone resulted in the suppression of subchondral bone deterioration and this effect was mediated by H-type vessel-induced ectopic bone formation. Further, articular cartilage degeneration was also alleviated after Y15 treatment. In vitro, the p-FAK level was significantly elevated in mesenchymal stem cells (MSCs) from vehicle-treated ACLT rats as compared to that in MSCs from sham controls and Y15-treated ACLT rats. Elevated p-FAK level in MSCs promoted vascular endothelial growth factor (VEGF) expression, as demonstrated from the high VEGF level in the blood, subchondral bone, and conditioned medium (CM) of MSCs from vehicle-treated ACLT rats. The CM of MSCs from vehicle-treated ACLT rats might promote the angiogenesis of endothelial cells and the catabolic response of chondrocytes through the FAK-growth factor receptor-bound protein 2-mitogen-activated protein kinase-mediated expression of VEGF. The effect of the CM from MSCs of Y15-treated ACLT rats or that treated with a VEGF-neutralizing antibody on vessel formation and the catabolic response was lowered. Thus, the specific inhibition of FAK signaling may be a promising avenue for the prevention or early treatment of OA.


Assuntos
Cartilagem Articular/metabolismo , Quinase 1 de Adesão Focal/antagonistas & inibidores , Proteína-Tirosina Quinases de Adesão Focal/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Osteoartrite/tratamento farmacológico , Alendronato/farmacologia , Animais , Ligamento Cruzado Anterior/patologia , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Osso e Ossos/patologia , Condrócitos/metabolismo , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Masculino , Osteoartrite/patologia , Ratos Sprague-Dawley
19.
Braz J Microbiol ; 51(3): 875-881, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32347530

RESUMO

This study aims to develop a rapid bacterial antibiotic susceptibility test (AST) method by Bacteria-aptamer@AgNPs-surface enhanced Raman spectroscopy (SERS) and further evaluate the influence of different antibiotics on the Raman intensity of bacteria. The Raman intensity of Escherichia coli O157:H7 (E. coli O157:H7) and Staphylococcus aureus (S. aureus) in the presence of different concentrations of antibiotics in 2 h was detected by Bacteria-aptamer@AgNPs-SERS in this study. Our results found that the bacteria Raman signal peak at 735 cm-1 and the minimum inhibitory concentration (MIC) value was determined in 1 h according to Raman signals. In 2 h, the bacteria Raman signal growth at sub-MIC concentrations of four different kinds of antibiotics and the bacteria colony-forming unit (CFU) have similar enhancements. SERS utilizes special functions of rough metal surfaces and offers a huge enhancement of Raman intensities with reduced fluorescence backgrounds, which makes it an ultrasensitive tool of detection. This rapid AST method and the enhancement effect should be of value in search of new antibiotic drugs.


Assuntos
Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana/métodos , Análise Espectral Raman/métodos , Aptâmeros de Nucleotídeos/química , Bactérias/química , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Nanopartículas Metálicas/química , Prata/química
20.
Stem Cell Res Ther ; 11(1): 131, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197645

RESUMO

BACKGROUND: Hypercholesterolemia increases the risk of tendon pain and tendon rupture. Tendon-derived stem cells (TDSCs) play a vital role in the development of tendinopathy. Our previous research found that high cholesterol inhibits tendon-related gene expression in TDSCs. Whether high cholesterol has other biological effects on TDSCs remains unknown. METHODS: TDSCs isolated from female SD rats were exposed to 10 mg/dL cholesterol for 24 h. Then, cell apoptosis was assessed using flow cytometry and fluorescence microscope. RFP-GFP-LC3 adenovirus transfection was used for measuring autophagy. Signaling transduction was measured by immunofluorescence and immunoblotting. In addition, Achilles tendons from ApoE -/- mice fed with a high-fat diet were histologically assessed using HE staining and immunohistochemistry. RESULTS: In this work, we verified that 10 mg/dL cholesterol suppressed cell proliferation and migration and induced G0/G1 phase arrest. Additionally, cholesterol induced apoptosis and autophagy simultaneously in TDSCs. Apoptosis induction was related to increased expression of cleaved caspase-3 and BAX and decreased expression of Bcl-xL. The occurrence of autophagic flux and accumulation of LC3-II demonstrated the induction of autophagy by cholesterol. Compared with the effects of cholesterol treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) enhanced apoptosis, while the apoptosis inhibitor Z-VAD-FMK diminished cholesterol-induced autophagy. Moreover, cholesterol triggered reactive oxygen species (ROS) generation and activated the AKT/FOXO1 pathway, while the ROS scavenger NAC blocked cholesterol-induced activation of the AKT/FOXO1 pathway. NAC and the FOXO1 inhibitor AS1842856 rescued the apoptosis and autophagy induced by cholesterol. Finally, high cholesterol elevated the expression of cleaved caspase-3, Bax, LC3-II, and FOXO1 in vivo. CONCLUSION: The present study indicated that high cholesterol induced apoptosis and autophagy through ROS-activated AKT/FOXO1 signaling in TDSCs, providing new insights into the mechanism of hypercholesterolemia-induced tendinopathy. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.


Assuntos
Hipercolesterolemia , Proteínas Proto-Oncogênicas c-akt , Animais , Apoptose , Autofagia , Linhagem Celular Tumoral , Colesterol , Feminino , Proteína Forkhead Box O1 , Camundongos , Proteínas do Tecido Nervoso , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Células-Tronco , Tendões
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