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1.
Sci Rep ; 14(1): 6553, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504116

RESUMO

Spinal cord injury (SCI) can cause a range of functional impairments, and patients with SCI have limited potential for functional recovery. Previous studies have demonstrated that autophagy plays a role in the pathological process of SCI, but the specific mechanism of autophagy in this context remains unclear. Therefore, we explored the role of autophagy in SCI by identifying key autophagy-related genes and pathways. This study utilized the GSE132242 expression profile dataset, which consists of four control samples and four SCI samples; autophagy-related genes were sourced from GeneCards. R software was used to screen differentially expressed genes (DEGs) in the GSE132242 dataset, which were then intersected with autophagy-related genes to identify autophagy-related DEGs in SCI. Subsequently, the expression levels of these genes were confirmed and analyzed with gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) analysis was conducted to identify interaction genes, and the resulting network was visualized with Cytoscape. The MCODE plug-in was used to build gene cluster modules, and the cytoHubba plug-in was applied to screen for hub genes. Finally, the GSE5296 dataset was used to verify the reliability of the hub genes. We screened 129 autophagy-related DEGs, including 126 up-regulated and 3 down-regulated genes. GO and KEGG pathway enrichment analysis showed that these 129 genes were mainly involved in the process of cell apoptosis, angiogenesis, IL-1 production, and inflammatory reactions, the TNF signaling pathway and the p53 signaling pathway. PPI identified 10 hub genes, including CCL2, TGFB1, PTGS2, FN1, HGF, MYC, IGF1, CD44, CXCR4, and SERPINEL1. The GSE5296 dataset revealed that the control group exhibited lower expression levels than the SCI group, although only CD44 and TGFB1 showed significant differences. This study identified 129 autophagy-related genes that might play a role in SCI. CD44 and TGFB1 were identified as potentially important genes in the autophagy process after SCI. These findings provide new targets for future research and offer new perspectives on the pathogenesis of SCI.


Assuntos
Perfilação da Expressão Gênica , Traumatismos da Medula Espinal , Humanos , Perfilação da Expressão Gênica/métodos , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos Testes , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Autofagia/genética , Biologia Computacional/métodos
2.
Mol Neurobiol ; 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38367135

RESUMO

M2 microglia transplantation has previously demonstrated beneficial effects on spinal cord injury (SCI) by regulating neuroinflammation and enhancing neuronal survival. Exosomes (EXOs), secreted by almost all cell types, embody partial functions and properties of their parent cells. However, the effect of M2 microglia-derived EXOs (M2-EXOs) on SCI recovery and the underlying molecular mechanisms remain unclear. In this study, we isolated M2-EXOs and intravenously introduced them into mice with SCI. Considering the reciprocal communication between microglia and astroglia in both healthy and injured central nervous systems (CNSs), we subsequently focused on the influence of M2-EXOs on astrocyte phenotype regulation. Our findings indicated that M2-EXOs promoted neuron survival and axon preservation, reduced the lesion area, inhibited A1 astrocyte activation, and improved motor function recovery in SCI mice. Moreover, they inhibited the nuclear translocation of p65 and the activation of the NF-κB signalling pathway in A1 astrocytes. Therefore, our research suggests that M2-EXOs mitigate the activation of neurotoxic A1 astrocytes by inhibiting the NF-κB signalling pathway, thereby improving spinal tissue preservation and motor function recovery following SCI. This positions M2-EXOs as a promising therapeutic strategy for SCI.

3.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(2): 155-161, 2024 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-38385227

RESUMO

Objective: To compare the intraoperative effects of computer navigation-assisted versus simple arthroscopic reconstruction of posterior cruciate ligament (PCL) tibial tunnel. Methods: The clinical data of 73 patients with PCL tears who were admitted between June 2021 and June 2022 and met the selection criteria were retrospectively analysed, of whom 34 cases underwent PCL tibial tunnel reconstruction with navigation-assisted arthroscopy (navigation group) and 39 cases underwent PCL tibial tunnel reconstruction with arthroscopy alone (control group). There was no significant difference in baseline data between the two groups, including gender, age, body mass index, side of injury, time from injury to surgery, preoperative posterior drawer test, knee range of motion (ROM), Tegner score, Lysholm score, and International Knee Documentation Committee (IKDC) score between the two groups ( P>0.05). The perioperative indicators (operation time and number of guide wire drillings) were recorded and compared between the two groups. The angle between the graft and the tibial tunnel and the exit positions of the tibial tunnel in the coronal, sagittal, and transverse planes respectively were measured on MRI at 1 day after operation. The knee ROM, Tegner score, Lysholm score, and IKDC score were evaluated before operation and at last follow-up. Results: The operation time in the navigation group was shorter than that in the control group, and the number of intraoperative guide wire drillings was less than that in the control group, the differences were significant ( P<0.05). Patients in both groups were followed up 12-17 months, with an average of 12.8 months. There was no perioperative complications such as vascular and nerve damage, deep venous thrombosis and infection of lower extremity. During the follow-up, there was no re-injuries in either group and no revision was required. The results showed that there was no significant difference in the exit positions of the tibial tunnel in the coronal, sagittal, and transverse planes between the two groups ( P>0.05), but the angle between the graft and the tibial tunnel was significantly greater in the navigation group than in the control group ( P<0.05). At last follow-up, 30, 3, 1 and 0 cases were rated as negative, 1+, 2+, and 3+ of posterior drawer test in the navigation group and 33, 5, 1, and 0 cases in the control group, respectively, which significantly improved when compared with the preoperative values ( P<0.05), but there was no significant difference between the two groups ( P>0.05). At last follow-up, ROM, Tegner score, Lysholm score, and IKDC score of the knee joint significantly improved in both groups when compared with preoperative values ( P<0.05), but there was no significant difference in the difference in preoperative and postoperative indicators between the two groups ( P>0.05). Conclusion: Computer-navigated arthroscopic PCL tibial tunnel reconstruction can quickly and accurately prepare tunnels with good location and orientation, with postoperative functional scores comparable to arthroscopic PCL tibial tunnel reconstruction alone.


Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Posterior , Humanos , Ligamento Cruzado Posterior/cirurgia , Ligamento Cruzado Posterior/lesões , Estudos Retrospectivos , Resultado do Tratamento , Articulação do Joelho/cirurgia , Tíbia/cirurgia , Artroscopia/métodos , Lesões do Ligamento Cruzado Anterior/cirurgia
4.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(2): 198-205, 2024 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-38385233

RESUMO

Objective: To investigate the effect of M2 microglia (M2-MG) transplantation on spinal cord injury (SCI) repair in mice. Methods: Primary MG were obtained from the cerebral cortex of 15 C57BL/6 mice born 2-3 days old by pancreatic enzyme digestion and identified by immunofluorescence staining of Iba1. Then the primary MG were co-cultured with interleukin 4 for 48 hours (experimental group) to induce into M2 phenotype and identified by immunofluorescence staining of Arginase 1 (Arg-1) and Iba1. The normal MG were harvested as control (control group). The dorsal root ganglion (DRG) of 5 C57BL/6 mice born 1 week old were co-cultured with M2-MG for 5 days to observe the axon length, the DRG alone was used as control. Forty-two 6-week-old female C57BL/6 mice were randomly divided into sham group ( n=6), SCI group ( n=18), and SCI+M2-MG group ( n=18). In sham group, only the laminae of T 10 level were removed; SCI group and SCI+M2-MG group underwent SCI modeling, and SCI+M2-MG group was simultaneously injected with M2-MG. The survival of mice in each group was observed after operation. At immediate (0), 3, 7, 14, 21, and 28 days after operation, the motor function of mice was evaluated by Basso Mouse Scale (BMS) score, and the gait was evaluated by footprint experiment at 28 days. The spinal cord tissue was taken after operation for immunofluorescence staining, in which glial fibrillary acidic protein (GFAP) staining at 7, 14, and 28 days was used to observe the injured area of the spinal cord, neuronal nuclei antigen staining at 28 days was used to observe the survival of neurons, and GFAP/C3 double staining at 7 and 14 days was used to observe the changes in the number of A1 astrocytes. Results: The purity of MG in vitro reached 90%, and the most of the cells were polarized into M2 phenotype identified by Arg-1 immunofluorescence staining. M2-MG promoted the axon growth when co-cultured with DRGs in vitro ( P<0.05). All groups of mice survived until the experiment was completed. The hind limb motor function of SCI group and SCI+M2-MG group gradually recovered over time. Among them, the SCI+M2-MG group had significantly higher BMS scores than the SCI group at 21 and 28 days ( P<0.05), and the dragging gait significantly improved at 28 days, but it did not reach the level of the sham group. Immunofluorescence staining showed that compared with the SCI group, the SCI+M2-MG group had a smaller injury area at 7, 14, and 28 days, an increase in neuronal survival at 28 days, and a decrease in the number of A1 astrocytes at 7 and 14 days, with significant differences ( P<0.05). Conclusion: M2-MG transplantation improves the motor function of the hind limbs of SCI mice by promoting neuron survival and axon regeneration. This neuroprotective effect is related to the inhibition of A1 astrocytes polarization.


Assuntos
Microglia , Traumatismos da Medula Espinal , Ratos , Camundongos , Animais , Feminino , Ratos Sprague-Dawley , Axônios/metabolismo , Regeneração Nervosa , Camundongos Endogâmicos C57BL , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo
5.
Front Neurorobot ; 17: 1301192, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023453

RESUMO

The objective of few-shot fine-grained learning is to identify subclasses within a primary class using a limited number of labeled samples. However, many current methodologies rely on the metric of singular feature, which is either global or local. In fine-grained image classification tasks, where the inter-class distance is small and the intra-class distance is big, relying on a singular similarity measurement can lead to the omission of either inter-class or intra-class information. We delve into inter-class information through global measures and tap into intra-class information via local measures. In this study, we introduce the Feature Fusion Similarity Network (FFSNet). This model employs global measures to accentuate the differences between classes, while utilizing local measures to consolidate intra-class data. Such an approach enables the model to learn features characterized by enlarge inter-class distances and reduce intra-class distances, even with a limited dataset of fine-grained images. Consequently, this greatly enhances the model's generalization capabilities. Our experimental results demonstrated that the proposed paradigm stands its ground against state-of-the-art models across multiple established fine-grained image benchmark datasets.

6.
Brief Bioinform ; 24(5)2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37594313

RESUMO

Accurate prediction of molecular properties is an important topic in drug discovery. Recent works have developed various representation schemes for molecular structures to capture different chemical information in molecules. The atom and motif can be viewed as hierarchical molecular structures that are widely used for learning molecular representations to predict chemical properties. Previous works have attempted to exploit both atom and motif to address the problem of information loss in single representation learning for various tasks. To further fuse such hierarchical information, the correspondence between learned chemical features from different molecular structures should be considered. Herein, we propose a novel framework for molecular property prediction, called hierarchical molecular graph neural networks (HimGNN). HimGNN learns hierarchical topology representations by applying graph neural networks on atom- and motif-based graphs. In order to boost the representational power of the motif feature, we design a Transformer-based local augmentation module to enrich motif features by introducing heterogeneous atom information in motif representation learning. Besides, we focus on the molecular hierarchical relationship and propose a simple yet effective rescaling module, called contextual self-rescaling, that adaptively recalibrates molecular representations by explicitly modelling interdependencies between atom and motif features. Extensive computational experiments demonstrate that HimGNN can achieve promising performances over state-of-the-art baselines on both classification and regression tasks in molecular property prediction.


Assuntos
Aprendizado Profundo , Redes Neurais de Computação , Aprendizagem , Descoberta de Drogas
7.
Mol Neurobiol ; 60(9): 5411-5425, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37316756

RESUMO

Ferroptosis plays crucial roles in the pathology of spinal cord injury (SCI). The purpose of this study was to identify differentially expressed ferroptosis-related genes (DE-FRGs) in human acute SCI by bioinformatics analysis and validate the hub DE-FRGs in non-SCI and SCI patients. The GSE151371 dataset was downloaded from the Gene Expression Omnibus and difference analysis was performed. The differentially expressed genes (DEGs) in GSE151371 overlapped with the ferroptosis-related genes (FRGs) obtained from the Ferroptosis Database. A total of 41 DE-FRGs were detected in 38 SCI samples and 10 healthy samples in GSE151371. Then, enrichment analyses of these DE-FRGs were performed for functional annotation. The GO enrichment results showed that upregulated DE-FRGs were mainly associated with reactive oxygen species and redox reactions, and the KEGG enrichment analysis indicated involvement in some diseases and ferroptosis pathways. Protein-protein interaction (PPI) analysis and lncRNA-miRNA-mRNA regulatory network were performed to explore the correlations between genes and regulatory mechanisms. The relationship between DE-FRGs and differentially expressed mitochondria-related genes (DE-MRGs) was also analyzed. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the hub DE-FRGs in clinical blood samples from acute SCI patients and healthy controls. Consistent with the bioinformatics results, qRT-PCR of the clinical samples indicated similar expression levels of TLR4, STAT3, and HMOX1. This study identified DE-FRGs in blood samples from SCI patients, and the results could improve our understanding of the molecular mechanisms of ferroptosis in SCI. These candidate genes and pathways could be therapeutic targets for SCI.


Assuntos
Ferroptose , MicroRNAs , Humanos , Ferroptose/genética , Biologia Computacional , DNA Mitocondrial , Bases de Dados Factuais
8.
Artigo em Inglês | MEDLINE | ID: mdl-36223356

RESUMO

Learning representations from data is a fundamental step for machine learning. High-quality and robust drug representations can broaden the understanding of pharmacology, and improve the modeling of multiple drug-related prediction tasks, which further facilitates drug development. Although there are a number of models developed for drug representation learning from various data sources, few researches extract drug representations from gene expression profiles. Since gene expression profiles of drug-treated cells are widely used in clinical diagnosis and therapy, it is believed that leveraging them to eliminate cell specificity can promote drug representation learning. In this paper, we propose a three-stage deep learning method for drug representation learning, named DRLM, which integrates gene expression profiles of drug-related cells and the therapeutic use information of drugs. Firstly, we construct a stacked autoencoder to learn low-dimensional compact drug representations. Secondly, we utilize an iterative clustering module to reduce the negative effects of cell specificity and noise in gene expression profiles on the low-dimensional drug representations. Thirdly, a therapeutic use discriminator is designed to incorporate therapeutic use information into the drug representations. The visualization analysis of drug representations demonstrates DRLM can reduce cell specificity and integrate therapeutic use information effectively. Extensive experiments on three types of prediction tasks are conducted based on different drug representations, and they show that the drug representations learned by DRLM outperform other representations in terms of most metrics. The ablation analysis also demonstrates DRLM's effectiveness of merging the gene expression profiles with the therapeutic use information. Furthermore, we input the learned representations into the machine learning models for case studies, which indicates its potential to discover new drug-related relationships in various tasks.

9.
Stem Cell Res Ther ; 13(1): 442, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056445

RESUMO

Traumatic central nervous system (CNS) disorders have catastrophic effects on patients, and, currently, there is no effective clinical treatment. Cell transplantation is a common treatment for traumatic CNS injury in animals. In recent years, an increasing number of studies have reported that the beneficial effect of transplanted cells for CNS repair is mediated primarily through the extracellular vesicles (EVs) secreted by the cells, in which microRNAs play a major role. Accordingly, numerous studies have evaluated the roles and applications of EVs secreted by different cell types in neurological diseases. Furthermore, due to their unique biological features, EVs are used as disease biomarkers and drug delivery systems for disease prevention and treatment. We discuss current knowledge related to EVs, focusing on the mechanism underlying their effects on traumatic CNS diseases, and summarize existing research on the potential clinical utility of EVs as disease biomarkers and drug delivery systems.


Assuntos
Doenças do Sistema Nervoso Central , Vesículas Extracelulares , MicroRNAs , Animais , Biomarcadores/metabolismo , Doenças do Sistema Nervoso Central/metabolismo , Doenças do Sistema Nervoso Central/terapia , Sistemas de Liberação de Medicamentos , Vesículas Extracelulares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
10.
Front Immunol ; 13: 969127, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911768

RESUMO

Microglia are important resident immune cells in the central nervous system (CNS) and play an important role in its development, homeostasis, and disease treatments. Activated microglia perform diverse functions in mouse models of CNS neurodegenerative diseases or deficits. In humans, microglia have been linked to various neurodegenerative diseases. Following brain or spinal cord injury, microglia express pro- and anti-inflammatory phenotypes at different stages of recovery. With the development of pharmacological and genetic tools for microglial depletion, studies have demonstrated that microglial depletion exerts both positive and negative effects in the treatment of CNS diseases. Notably, microglial depletion provides an empty niche that stimulates production of new microglia. Microglial depletion and repopulation can not only treat diseases by eliminating dysfunctional microglia but can also provide an indication of the molecular mechanisms of diseases. Although this approach has shown impressive results, its use is still in its infancy. In this review, we summarize the current pharmacological and genetic tools for microglial depletion and highlight recent advances in microglial repopulation therapy for the treatment and functional recovery of neurological diseases and deficits. Finally, we briefly discuss the therapeutic challenges and prospective uses of microglial repopulation therapy.


Assuntos
Doenças Neurodegenerativas , Traumatismos do Sistema Nervoso , Animais , Encéfalo , Sistema Nervoso Central , Humanos , Camundongos , Microglia , Doenças Neurodegenerativas/terapia
11.
Front Neurosci ; 16: 800513, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250447

RESUMO

Spinal cord injury (SCI) can result in sensorimotor impairments or disability. Studies of the cellular response to SCI have increased our understanding of nerve regenerative failure following spinal cord trauma. Biological, engineering and rehabilitation strategies for repairing the injured spinal cord have shown impressive results in SCI models of both rodents and non-human primates. Cell transplantation, in particular, is becoming a highly promising approach due to the cells' capacity to provide multiple benefits at the molecular, cellular, and circuit levels. While various cell types have been investigated, we focus on the use of Schwann cells (SCs) to promote SCI repair in this review. Transplantation of SCs promotes functional recovery in animal models and is safe for use in humans with subacute SCI. The rationales for the therapeutic use of SCs for SCI include enhancement of axon regeneration, remyelination of newborn or sparing axons, regulation of the inflammatory response, and maintenance of the survival of damaged tissue. However, little is known about the molecular mechanisms by which transplanted SCs exert a reparative effect on SCI. Moreover, SC-based therapeutic strategies face considerable challenges in preclinical studies. These issues must be clarified to make SC transplantation a feasible clinical option. In this review, we summarize the recent advances in SC transplantation for SCI, and highlight proposed mechanisms and challenges of SC-mediated therapy. The sparse information available on SC clinical application in patients with SCI is also discussed.

12.
Front Physiol ; 13: 1078087, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36589414

RESUMO

Background: Balance impairment is the most common risk factor for falls among older adults, with three potential factors (tactile sensation, proprioception, and muscle strength) being responsible for their balance control. However, controversies remain on whether or not balance control is related to the three contributors among older adults. Therefore, clarifying the above questions helps explain the mechanisms of increased falls among senior older adults. This study compares the balance control and the three factors and investigates their relationships among older adults of different ages. Methods: 166 participants ultimately passed the qualification assessment and were categorized into younger (YG, 60-69 years, n = 56), middle (MG, 70-79 years, n = 57), or older (OG, ≥80 years, n = 53) aged groups. Berg Balance Scale (BBS) performance, tactile sensation, proprioception, and muscle strength were tested. One-way ANOVA and partial correlation were performed to explore the differences between groups in BBS and its three potential contributors, along with the correlations between them within each age group. Results: Significant differences among the three groups were detected in BBS scores (p < 0.001), tactile sensation at the great toe (p = 0.015) and heel (p = 0.025), proprioception of knee flexion (p < 0.001) and extension (p < 0.001), and ankle plantarflexion (p < 0.001) and dorsiflexion (p < 0.001), and muscle strength of ankle plantarflexion (p < 0.001) and dorsiflexion (p < 0.001), and hip abduction (p < 0.001). Proprioception of knee flexion (r = -0.351, p = 0.009) and extension (r = -0.276, p = 0.041), and ankle plantarflexion (r = -0.283, p = 0.036), and muscle strength of ankle plantarflexion (r = 0.326, p = 0.015) and hip abduction (r = 0.415, p = 0.002) were correlated with BBS among the YG. Proprioception of ankle plantarflexion (r = -0.291, p = 0.030) and muscle strength of ankle plantarflexion (r = 0.448, p = 0.001) and dorsiflexion (r = 0.356, p = 0.007) were correlated with BBS among the MG. Muscle strength of ankle plantarflexion (r = 0.276, p = 0.039) and hip abduction (r = 0.324, p = 0.015) were correlated with BBS among the OG. Conclusion: YG and MG had better balance control, tactile sensation, proprioception, and muscle strength compared to OG. Proprioception correlated with balance control in YG and MG, but not in the OG. The worsen proprioception among the OG could be the key for increased falls. Exercise should be recommended to improve proprioception among senior older adults.

13.
Front Physiol ; 13: 1070754, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36589446

RESUMO

Background: Knee osteoarthritis (KOA) is one of the most common chronic progressive diseases with degenerative destruction of articular cartilage and bone, leading to knee pain, impaired proprioception, and reduced functional performance. This study was to investigate the effects of an 8-week Traditional Chinese herb hot compress (TCHHC) combined with therapeutic exercise (TE) on pain, proprioception, and functional performance among older adults with KOA. Methods: Twenty-seven older adults with KOA were recruited and randomly assigned to the TCHHC + TE or TE groups. Thirteen participants received TCHHC + TE, and fourteen received TE. At pre- (week 0) and post-intervention (week 9), their pain, joint proprioception, and functional performance were measured. Two-way ANOVA with repeated measures was adopted to analyze the data. Results: Compared with week 0, the pain score, proprioception thresholds of knee extension and ankle plantarflexion, and the times of TUG and 20-m walk tests decreased more significantly in the TCHHC + TE group than in the TE group at week 9. Conclusion: Compared with TE, the 8-week TCHHC + TE was superior in relieving pain, recovering proprioception, and improving functional performance among older adults with KOA. It is recommended that TCHHC should be adopted prior to TE to enhance the effects of KOA rehabilitation.

14.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34727569

RESUMO

Predicting the response of a cancer cell line to a therapeutic drug is an important topic in modern oncology that can help personalized treatment for cancers. Although numerous machine learning methods have been developed for cancer drug response (CDR) prediction, integrating diverse information about cancer cell lines, drugs and their known responses still remains a great challenge. In this paper, we propose a graph neural network method with contrastive learning for CDR prediction. GraphCDR constructs a graph neural network based on multi-omics profiles of cancer cell lines, the chemical structure of drugs and known cancer cell line-drug responses for CDR prediction, while a contrastive learning task is presented as a regularizer within a multi-task learning paradigm to enhance the generalization ability. In the computational experiments, GraphCDR outperforms state-of-the-art methods under different experimental configurations, and the ablation study reveals the key components of GraphCDR: biological features, known cancer cell line-drug responses and contrastive learning are important for the high-accuracy CDR prediction. The experimental analyses imply the predictive power of GraphCDR and its potential value in guiding anti-cancer drug selection.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Aprendizado de Máquina , Neoplasias/tratamento farmacológico , Redes Neurais de Computação
15.
Bioinformatics ; 38(2): 426-434, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34499148

RESUMO

MOTIVATION: There are various interaction/association bipartite networks in biomolecular systems. Identifying unobserved links in biomedical bipartite networks helps to understand the underlying molecular mechanisms of human complex diseases and thus benefits the diagnosis and treatment of diseases. Although a great number of computational methods have been proposed to predict links in biomedical bipartite networks, most of them heavily depend on features and structures involving the bioentities in one specific bipartite network, which limits the generalization capacity of applying the models to other bipartite networks. Meanwhile, bioentities usually have multiple features, and how to leverage them has also been challenging. RESULTS: In this study, we propose a novel multi-view graph convolution network (MVGCN) framework for link prediction in biomedical bipartite networks. We first construct a multi-view heterogeneous network (MVHN) by combining the similarity networks with the biomedical bipartite network, and then perform a self-supervised learning strategy on the bipartite network to obtain node attributes as initial embeddings. Further, a neighborhood information aggregation (NIA) layer is designed for iteratively updating the embeddings of nodes by aggregating information from inter- and intra-domain neighbors in every view of the MVHN. Next, we combine embeddings of multiple NIA layers in each view, and integrate multiple views to obtain the final node embeddings, which are then fed into a discriminator to predict the existence of links. Extensive experiments show MVGCN performs better than or on par with baseline methods and has the generalization capacity on six benchmark datasets involving three typical tasks. AVAILABILITY AND IMPLEMENTATION: Source code and data can be downloaded from https://github.com/fuhaitao95/MVGCN. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Biologia Computacional , Software , Humanos , Doença
17.
Cell Death Dis ; 12(12): 1085, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785659

RESUMO

Nuclear transfer embryonic stem cells (ntESCs) hold enormous promise for individual-specific regenerative medicine. However, the chromatin states of ntESCs remain poorly characterized. In this study, we employed ATAC-seq and Hi-C techniques to explore the chromatin accessibility and three-dimensional (3D) genome organization of ntESCs. The results show that the chromatin accessibility and genome structures of somatic cells are re-arranged to ESC-like states overall in ntESCs, including compartments, topologically associating domains (TADs) and chromatin loops. However, compared to fertilized ESCs (fESCs), ntESCs show some abnormal openness and structures that have not been reprogrammed completely, which impair the differentiation potential of ntESCs. The histone modification H3K9me3 may be involved in abnormal structures in ntESCs, including incorrect compartment switches and incomplete TAD rebuilding. Moreover, ntESCs and iPSCs show high similarity in 3D genome structures, while a few differences are detected due to different somatic cell origins and reprogramming mechanisms. Through systematic analyses, our study provides a global view of chromatin accessibility and 3D genome organization in ntESCs, which can further facilitate the understanding of the similarities and differences between ntESCs and fESCs.


Assuntos
Cromatina/metabolismo , Células-Tronco Embrionárias/metabolismo , Técnicas de Transferência Nuclear/normas , Animais , Diferenciação Celular , Feminino , Humanos , Camundongos
18.
J Phys Condens Matter ; 33(30)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-33794513

RESUMO

Gas sensor technology is widely utilized in various areas ranging from home security, environment and air pollution, to industrial production. It also hold great promise in non-invasive exhaled breath detection and an essential device in future internet of things. The past decade has witnessed giant advance in both fundamental research and industrial development of gas sensors, yet current efforts are being explored to achieve better selectivity, higher sensitivity and lower power consumption. The sensing layer in gas sensors have attracted dominant attention in the past research. In addition to the conventional metal oxide semiconductors, emerging nanocomposites and graphene-like two-dimensional materials also have drawn considerable research interest. This inspires us to organize this comprehensive 2020 gas sensing materials roadmap to discuss the current status, state-of-the-art progress, and present and future challenges in various materials that is potentially useful for gas sensors.

19.
Neural Regen Res ; 16(3): 573-579, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32985490

RESUMO

Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits. In previous epidural electrical stimulation studies, single electrode sites and continuous tetanic stimulation have often been used. With this stimulation, the body is prone to declines in tolerance and locomotion coordination. In the present study, rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers, and were then subjected to epidural electrical stimulation. The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment. Simultaneously, the electrode stimulation site was able to be accurately applied to the L2-3 and S1 segments of the spinal cord. To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes, GFAP/Iba-1 double-labeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation. Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation, and there was no activated Iba-1+ cell aggregation, indicating that the implant did not cause an inflammatory response in the spinal cord. Rat gait analysis showed that, at 3 days after surgery, gait became coordinated in rats with spinal cord injury under burst stimulation. The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution. To evaluate the matching degree between the flexible epidural electrode (including three stimulation contacts), vertebral morphology, and the level of the epidural site of the stimulation electrode, micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation. Based on the experimental results of gait recovery using three-site stimulation electrodes at L2-3 and S1 combined with burst stimulation in a rat model of spinal cord injury, epidural electrical stimulation is a promising protocol that needs to be further explored. This study was approved by the Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2019-X15-39) on April 19, 2019.

20.
BMC Genomics ; 21(1): 746, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109075

RESUMO

BACKGROUND: In diploid cells, it is important to construct maternal and paternal Hi-C contact maps respectively since the two homologous chromosomes can differ in chromatin three-dimensional (3D) organization. Though previous softwares could construct diploid (maternal and paternal) Hi-C contact maps by using phased genetic variants, they all neglected the systematic biases in diploid Hi-C contact maps caused by variable genetic variant density in the genome. In addition, few of softwares provided quantitative analyses on allele-specific chromatin 3D organization, including compartment, topological domain and chromatin loop. RESULTS: In this work, we revealed the feature of allele-assignment bias caused by the variable genetic variant density, and then proposed a novel strategy to correct the systematic biases in diploid Hi-C contact maps. Based on the bias correction, we developed an integrated tool, called HiCHap, to perform read mapping, contact map construction, whole-genome identification of compartments, topological domains and chromatin loops, and allele-specific testing for diploid Hi-C data. Our results show that the correction on allele-assignment bias in HiCHap does significantly improve the quality of diploid Hi-C contact maps, which subsequently facilitates the whole-genome identification of diploid chromatin 3D organization, including compartments, topological domains and chromatin loops. Finally, HiCHap also supports the data analysis for haploid Hi-C maps without distinguishing two homologous chromosomes. CONCLUSIONS: We provided an integrated package HiCHap to perform the data processing, bias correction and structural analysis for diploid Hi-C data. The source code and tutorial of software HiCHap are freely available at https://pypi.org/project/HiCHap/ .


Assuntos
Cromatina , Diploide , Cromatina/genética , Cromossomos , Análise de Dados , Software
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