Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 136
Filtrar
1.
BMC Musculoskelet Disord ; 23(1): 49, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35031036

RESUMO

BACKGROUND: Femoral neck fractures in young people are usually Pauwels Type III fractures. The common treatment method are multiple parallel cannulated screws or dynamic hip screw sliding compression fixation. Due to the huge shear stress, the rate of complications such as femoral head necrosis and nonunion is still high after treatment. The aim of our study was to compare the stabilities of two fixation methods in fixating pauwels type III femoral neck fractures. METHODS: All biomimetic fracture samples are fixed with three cannulated screws combined with a medial buttress plate. There were two fixation groups for the buttress plate and proximal fracture fragment: Group A, long screw (40 mm); Group B, short screw (6 mm). Samples were subjected to electrical strain measurement under a load of 500 N, axial stiffness was measured, and then the samples were axially loaded until failure. More than 5 mm of displacement or synthetic bone fracture was considered as construct failure. RESULTS: There were no significant differences in failure load (P = 0.669), stiffness (P = 0.842), or strain distribution (P > 0.05) between the two groups. CONCLUSIONS: Unicortical short screws can provide the same stability as long screws for Pauwels Type III Femoral Neck Fractures.

2.
Front Cell Infect Microbiol ; 11: 636999, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869048

RESUMO

Background: Coronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients. Methods: Patient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality. Results: Logistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19. Conclusion: Elevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.

3.
Ultrason Sonochem ; 82: 105893, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34969000

RESUMO

The cavitation characteristics during the spreading of a pure Sn liquid droplet subjected to ultrasonication were studied for the first time through high-speed photography to reveal the wetting mechanism. Ultrasonic vibration realized the spreading of Sn droplet on the nonwetting pure Al substrate. However, the oxide layer of the substrate at the spreading front is difficult to remove. The high-speed photography result shows that a noncavitation region consistently appears at the spreading front, because the acoustic pressure is below the cavitation threshold of 1.26 MPa. In particular, the width of the noncavitation region gradually increases as the size of the spreading area increases. Such a result accounts for the condition wherein the oxide layer at the spreading front is difficult to remove. Furthermore, the bubble density during spreading gradually decreases due to the decreased acoustic pressure of the thinned liquid. Finally, the bubble dynamics were calculated to verify the wetting mechanism.

4.
Contrast Media Mol Imaging ; 2021: 3309382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34949969

RESUMO

In order to monitor the effect of nerve block in postoperative analgesia more accurately, this paper puts forward the application research of ultrasonic real-time intelligent monitoring of nerve block in postoperative analgesia. Ultrasonic real-time intelligent monitoring of nerve block in upper limb surgery, lower limb surgery, and abdominal surgery combined with the nerve stimulator. The experiments show that there are 5 cases of adverse reactions when the nerve stimulator is only used, but no adverse reactions occur when combined with ultrasound-guided block. Continuous subclavian brachial plexus block with the ultrasound-guided nerve stimulator can clearly see the subclavian brachial plexus and its surrounding tissue structure, the direction of needle insertion in the plane, and the diffusion of narcotic drugs. The average success rate of block was up to 95.2%, which was significantly higher than that of nerve stimulator alone, and the success rate of recatheterization after the first failure was also improved. The average postoperative analgesia satisfaction was 85.6%, the average operation time was only 20 min, and the subclavian artery and pleura were avoided effectively. No pneumothorax and other complications occurred. The average success rate of ultrasound-guided subclavicular brachial plexus block in 1-2-year-old children was 97%, which was much higher than the average success rate of nerve stimulator localization with 63%. Ultrasound-guided nerve block not only directly blocks nerves under visual conditions but also helps to observe the structures around nerves and dynamically observe the diffusion of local anesthetics, which can significantly improve the accuracy and success rate of nerve block and reduce the incidence of complications.

6.
BMC Musculoskelet Disord ; 22(1): 810, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548069

RESUMO

BACKGROUND: Femoral neck fracture combined with anterior dislocation of the femoral head is very rare. To our knowledge, there is no classification system yet for this rare form of injury, and the injury mechanism of femoral neck fracture combined with obturator head dislocation has not been described in the literature. In this study, we systematically reviewed the literature and the cases treated in our hospital, and identified and classified all injury types according to the injury mechanism of femoral neck fracture combined with anterior dislocation of the femoral head. Further, based on the experience of treating a patient with femoral neck fracture and obturator dislocation of the femoral head, a theoretical hypothesis was proposed for the injury mechanism of this rare type of injury. METHODS: A comprehensive search was conducted on PubMed, WOS, CNKI database. These fractures were classified according to the dislocation site and injury mechanism (one injury or two injuries). RESULTS: 1891 articles were initially identified through PubMed and other databases, and after bibliographic research, study screening, and removing duplicates, 1455 articles were selected. After applying the exclusion criteria, a total of 18 full-text articles describing femoral neck fractures combined with anterior dislocation of the femoral head. Different dislocation sites have different injury mechanisms. Our classification system, to the best of the authors' knowledge, allowed us to include all types of femoral neck fractures combined with anterior dislocation of the femoral head from the literature. According to the proposed classification system, the morphological features of femoral neck fracture combined with anterior dislocation of the femoral head can be accurately conveyed between doctors. CONCLUSIONS: All injury patterns can likely be identified using the proposed classification system. This can help avoid confusion in the nomenclature of femoral neck fractures combined with anterior dislocation of the femoral head and help surgeons to more accurately detect lesions, thereby guiding surgical treatment.


Assuntos
Fraturas do Colo Femoral , Luxação do Quadril , Luxações Articulares , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Fixação Interna de Fraturas , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/etiologia , Luxação do Quadril/cirurgia , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/etiologia , Luxações Articulares/cirurgia
7.
Neuroreport ; 32(13): 1147-1152, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34334778

RESUMO

OBJECTIVE: This study aimed to explore the epigenetic regulation of activity-dependent and exon-specific brain-derived neurotrophic factor (BDNF) expression under KCl depolarization in primary cortical neurons. METHODS: We investigated BDNF exon I, exon IV and the growth arrest and DNA damage-inducible protein 45 alpha (Gadd45α) transcription levels under KCl-induced neuronal activation in postmitotic neurons. Gadd45α occupancy at BDNF I and IV promoter was measured by chromatin immunoprecipitation (ChIP) followed by quantitative PCR; DNA methylation level was checked by methylated DNA immunoprecipitation (MeDIP) followed by qPCR. In addition, lentiviral shRNA targeting Gadd45α was used to knockdown Gadd45α expression. RESULTS: BDNF exon I and IV mRNA expressions were both highly induced by KCl depolarization. However, ChIP analysis demonstrated a significantly increased Gadd45α occupancy only at the BDNF P1 promotor, but not P4, which is associated with reducing DNA methylation within BDNF P1 promoter. Furthermore, after the lentiviral-mediated knockdown of Gadd45α, the increased Gadd45α occupancy at the BDNF P1 was inhibited, which was accompanying the complete blocking of the demethylation effect at P1. Nonetheless, the induction of BDNF exon I mRNA by KCl was only partially prevented by Gadd45α shRNA, indicting other mechanisms involved in regulating BDNF exon I expression. CONCLUSIONS: DNA demethylation mediated by Gadd45α protein involves promoting the regulation of activity-dependent BDNF exon I expression in neurons.

8.
Ther Adv Chronic Dis ; 12: 2040622321995685, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457228

RESUMO

Background: Previous studies reported that melatonin exerts its effect on mesenchymal stem cell (MSC) survival and differentiation into osteogenic and adipogenic lineage. In the current study we aimed to explore the effect of melatonin on osteoporosis and relevant mechanisms. Methods: Real-time qualitative polymerase chain reaction (RT-qPCR) and Western blot analysis were conducted to determine expression of HGF, PTEN, and osteoblast differentiation-related genes in ovariectomy (OVX)-induced osteoporosis mice and the isolated bone marrow MSCs (BMSCs). Pre-conditioning with melatonin (1 µmol/l, 10 µmol/l and 100 µmol/l) was carried out in OVX mice BMSCs. Bone microstructure was analyzed using micro-computed tomography and the contents of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase 5b (TRAP5b) were detected by enzyme-linked immunosorbent assay in serum. BMSC proliferation was measured by cell-counting kit (CCK)-8 assay. Alizarin red S (ARS) staining and ALP activity assay were performed to assess BMSC mineralization and calcification. The activity of the Wnt/ß-catenin pathway was evaluated by dual-luciferase reporter assay. Results: Melatonin prevented bone loss in OVX mice. Melatonin increased ALP expression and reduced TRAP5b expression. HGF and ß-catenin were downregulated, while PTEN was upregulated in the femur of OVX mice. Melatonin elevated HGF expression and then stimulated BMSC proliferation and osteogenic differentiation. Additionally, HGF diminished the expression of PTEN, resulting in activated Wnt/ß-catenin pathway both in vitro and in vivo. Furthermore, melatonin was shown to ameliorate osteoporosis in OVX mice via the HGF/PTEN/Wnt/ß-catenin axis. Conclusion: Melatonin could potentially enhance osteogenic differentiation of BMSCs and retard bone loss through the HGF/PTEN/Wnt/ß-catenin axis.

9.
BMC Med Inform Decis Mak ; 21(Suppl 1): 254, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461870

RESUMO

BACKGROUND: Accumulating studies indicates that microRNAs (miRNAs) play vital roles in the process of development and progression of many human complex diseases. However, traditional biochemical experimental methods for identifying disease-related miRNAs cost large amount of time, manpower, material and financial resources. METHODS: In this study, we developed a framework named hybrid collaborative filtering for miRNA-disease association prediction (HCFMDA) by integrating heterogeneous data, e.g., miRNA functional similarity, disease semantic similarity, known miRNA-disease association networks, and Gaussian kernel similarity of miRNAs and diseases. To capture the intrinsic interaction patterns embedded in the sparse association matrix, we prioritized the predictive score by fusing three types of information: similar disease associations, similar miRNA associations, and similar disease-miRNA associations. Meanwhile, singular value decomposition was adopted to reduce the impact of noise and accelerate predictive speed. RESULTS: We then validated HCFMDA with leave-one-out cross-validation (LOOCV) and two types of case studies. In the LOOCV, we achieved 0.8379 of AUC (area under the curve). To evaluate the performance of HCFMDA on real diseases, we further implemented the first type of case validation over three important human diseases: Colon Neoplasms, Esophageal Neoplasms and Prostate Neoplasms. As a result, 44, 46 and 44 out of the top 50 predicted disease-related miRNAs were confirmed by experimental evidence. Moreover, the second type of case validation on Breast Neoplasms indicates that HCFMDA could also be applied to predict potential miRNAs towards those diseases without any known associated miRNA. CONCLUSIONS: The satisfactory prediction performance demonstrates that our model could serve as a reliable tool to guide the following research for identifying candidate miRNAs associated with human diseases.


Assuntos
Biologia Computacional , MicroRNAs , Neoplasias/genética , Algoritmos , Predisposição Genética para Doença , Humanos , MicroRNAs/genética
10.
Curr Med Sci ; 41(4): 782-787, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34403104

RESUMO

OBJECTIVE: Combined surgical and endovascular treatment for vascular disorders has become prevalent in recent years. However, reports on one-session hybrid surgery for arteriovenous malformations (AVMs) are relatively rare. The safety and efficiency of combined treatment for brain AVMs were analyzed in biplanar hybrid operating room (OR) at one stage. METHODS: We retrospectively analyzed 20 patients with AVMs undergoing combined surgical and endovascular treatment from October 2015 to June 2018. The data for resection rate, microcatheter adhesion, surgical position and postoperative outcomes were analyzed. Total resection or near-total resection was achieved in all cases. RESULTS: A total of 13 patients were under combined endovascular and surgical procedures, and 7 experienced surgery with intraoperative digital subtraction angiography. Sitting position was applied in 3 of them; 2 niduses in cerebellum, and 1 in parietal lobe. Compared with admission modified Rankin Scale (mRS) in all patients, postoperative 12-month mRS showed a significant decline. Besides, 3 patients experienced microcatheter adhesion after endovascular embolization, thereafter underwent surgical adhesion removal while nidus resection was done. CONCLUSION: Combined endovascular and surgical modality in a hybrid OR at one stage provides a safe strategy for the treatment of AVMs. The biplanar hybrid neurointerventional suite is endowed with unconstrained operating angle which enables combined endovascular and surgical treatment in sitting position. It also reduces the risk of microcatheter adhesion, which enables interventional radiologists to perform aggressively.

11.
Front Med (Lausanne) ; 8: 687220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195213

RESUMO

Purpose: The coronavirus disease (COVID-19) pandemic poses a global threat, and identification of its prognostic biomarkers could prove invaluable. Fibrinogen (FIB) could be one such indicator as coagulation and fibrinolysis abnormalities are common among COVID-19 patients. We examined the role of FIB levels in the prognosis of COVID-19. Methods: This retrospective cohort study enrolled 1,643 COVID-19 patients from the Leishenshan Hospital in Wuhan, China. The follow-up was conducted from February 8, 2020 to April 15, 2020. The cohort was divided into three groups according to the FIB level on admission, and associations with mortality and disease severity were determined using Cox and logistic regression analyses, respectively. Further, Kaplan-Meier (K-M) analyses by log-rank tests were used to assess the survival of patients with varying FIB levels. Results: Patients with FIB < 2.2 g/L [hazard ratio (HR): 9.02, 95% confidence interval (CI): 1.91-42.59, P = 0.006] and >4.2 g/L (HR: 4.79, 95% CI: 1.14-20.20, P = 0.033) showed higher mortality risks compared to those with FIB between 2.2 and 4.2 g/L. The survival curves showed similar results in K-M analyses (P < 0.001). Additionally, an elevated FIB level was associated with a greater risk of developing critical disease (odds ratio: 2.16, 95% CI: 1.04-4.46, P = 0.038) than a FIB level within the normal range. Conclusion: Abnormal FIB levels may be associated with mortality risk among COVID-19 patients and could predict critical disease development. Thus, assessment of FIB levels may assist in determining the prognosis of COVID-19 patients.

12.
Math Biosci Eng ; 18(4): 3755-3780, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-34198411

RESUMO

Computer vision technologies have been widely implemented in the defect detection. However, most of the existing detection methods generally require images with high quality, and they can only process code characters on simple backgrounds with high contrast. In this paper, a defect detection approach based on deep learning has been proposed to efficiently perform defect detection of code characters on complex backgrounds with a high accuracy. Specifically, image processing algorithms and data enhancement techniques were utilized to generate a large number of defect samples to construct a large data set featuring a balanced positive and negative sample ratio. The object detection network called BBE was build based on the core module of EfficientNet. Experimental results show that the mAP of the model and the accuracy reach 0.9961 and 0.9985, respectively. Individual character detection results were screened by setting relevant quality inspection standards to evaluate the overall quality of the code characters, the results of which have verified the effectiveness of the proposed method for industrial production. Its accuracy and speed are high with high robustness and transferability to other similar defect detection tasks. To the best of our knowledge, this report describes the first time that the BBE has been applied to defect inspections for real plastic container industry.


Assuntos
Algoritmos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador
13.
Brief Bioinform ; 22(4)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34293850

RESUMO

Emerging evidence indicates that the abnormal expression of miRNAs involves in the evolution and progression of various human complex diseases. Identifying disease-related miRNAs as new biomarkers can promote the development of disease pathology and clinical medicine. However, designing biological experiments to validate disease-related miRNAs is usually time-consuming and expensive. Therefore, it is urgent to design effective computational methods for predicting potential miRNA-disease associations. Inspired by the great progress of graph neural networks in link prediction, we propose a novel graph auto-encoder model, named GAEMDA, to identify the potential miRNA-disease associations in an end-to-end manner. More specifically, the GAEMDA model applies a graph neural networks-based encoder, which contains aggregator function and multi-layer perceptron for aggregating nodes' neighborhood information, to generate the low-dimensional embeddings of miRNA and disease nodes and realize the effective fusion of heterogeneous information. Then, the embeddings of miRNA and disease nodes are fed into a bilinear decoder to identify the potential links between miRNA and disease nodes. The experimental results indicate that GAEMDA achieves the average area under the curve of $93.56\pm 0.44\%$ under 5-fold cross-validation. Besides, we further carried out case studies on colon neoplasms, esophageal neoplasms and kidney neoplasms. As a result, 48 of the top 50 predicted miRNAs associated with these diseases are confirmed by the database of differentially expressed miRNAs in human cancers and microRNA deregulation in human disease database, respectively. The satisfactory prediction performance suggests that GAEMDA model could serve as a reliable tool to guide the following researches on the regulatory role of miRNAs. Besides, the source codes are available at https://github.com/chimianbuhetang/GAEMDA.


Assuntos
Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Modelos Genéticos , Neoplasias , Redes Neurais de Computação , RNA Neoplásico , Software , Humanos , MicroRNAs/biossíntese , MicroRNAs/genética , Neoplasias/genética , Neoplasias/metabolismo , RNA Neoplásico/biossíntese , RNA Neoplásico/genética
14.
J Clin Invest ; 131(16)2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34228644
15.
iScience ; 24(6): 102455, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34041455

RESUMO

Predicting the microRNA-disease associations by using computational methods is conductive to the efficiency of costly and laborious traditional bio-experiments. In this study, we propose a computational machine learning-based method (DANE-MDA) that preserves integrated structure and attribute features via deep attributed network embedding to predict potential miRNA-disease associations. Specifically, the integrated features are extracted by using deep stacked auto-encoder on the diverse orders of matrixes containing structure and attribute information and are then trained by using random forest classifier. Under 5-fold cross-validation experiments, DANE-MDA yielded average accuracy, sensitivity, and AUC at 85.59%, 84.23%, and 0.9264 in term of HMDD v3.0 dataset, and 83.21%, 80.39%, and 0.9113 in term of HMDD v2.0 dataset, respectively. Additionally, case studies on breast, colon, and lung neoplasms related disease show that 47, 47, and 46 of the top 50 miRNAs can be predicted and retrieved in the other database.

16.
Sci Adv ; 7(15)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33837084

RESUMO

Cells in vivo generate mechanical traction on the surrounding 3D extracellular matrix (ECM) and neighboring cells. Such traction and biochemical cues may remodel the matrix, e.g., increase stiffness, which, in turn, influences cell functions and forces. This dynamic reciprocity mediates development and tumorigenesis. Currently, there is no method available to directly quantify single-cell forces and matrix remodeling in 3D. Here, we introduce a method to fulfill this long-standing need. We developed a high-resolution microfabricated sensor that hosts a 3D cell-ECM tissue formed by self-assembly. This sensor measures cell forces and tissue stiffness and can apply mechanical stimulation to the tissue. We measured single and multicellular force dynamics of fibroblasts (3T3), human colon (FET) and lung (A549) cancer cells, and cancer-associated fibroblasts (CAF05) with 1-nN resolution. Single cells show notable force fluctuations in 3D. FET/CAF coculture system, mimicking cancer tumor microenvironment, increased tissue stiffness by three times within 24 hours.

17.
Nucleic Acids Res ; 49(7): 3796-3813, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33744966

RESUMO

The family of Poly(A)-binding proteins (PABPs) regulates the stability and translation of messenger RNAs (mRNAs). Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC). Recently, we have shown that MKRN3 epigenetically regulates the transcription of GNRH1 through conjugating poly-Ub chains onto methyl-DNA bind protein 3 (MBD3). Therefore, MKRN3-mediated ubiquitin signalling could control both transcriptional and post-transcriptional switches of mammalian puberty initiation. While identifying MKRN3 as a novel tissue-specific translational regulator, our work also provided new mechanistic insights into the etiology of MKRN3 dysfunction-associated human CPP.


Assuntos
Hormônio Liberador de Gonadotropina/genética , Proteínas de Ligação a Poli(A)/metabolismo , Precursores de Proteínas/genética , Puberdade Precoce , RNA Mensageiro/metabolismo , Ubiquitina-Proteína Ligases/fisiologia , Animais , Células HEK293 , Células HeLa , Humanos , Camundongos , Camundongos Knockout , Puberdade Precoce/genética , Puberdade Precoce/metabolismo , Ubiquitinação
18.
Mol Med Rep ; 23(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33649841

RESUMO

Recent studies have reported that gene amplified in squamous cell carcinoma 1 (GASC1) is involved in the progression of several types of cancer. However, whether GASC1 promotes glioma progression remains unknown. Therefore, the present study aimed to investigate the effect of GASC1 exposure on glioma tumorigenesis. The western blot demonstrated that grade III and IV glioma tissues exhibited a higher mRNA and protein expression of GASC1. Moreover, CD133+ U87 or U251 cells from magnetic cell separation exhibited a higher GASC1 expression. Invasion Transwell assay, clonogenic assay and wound healing assay have shown that GASC1 inhibition using a pharmacological inhibitor and specific short hairpin (sh)RNA suppressed the invasive, migratory and tumorsphere forming abilities of primary culture human glioma cells. Furthermore, GASC1­knockdown decreased notch receptor (Notch) responsive protein hes family bHLH transcription factor 1 (Hes1) signaling. GASC1 inhibition reduced notch receptor 1 (NOTCH1) expression, and a NOTCH1 inhibitor enhanced the effects of GASC1 inhibition on the CD133+ U87 or U251 cell tumorsphere forming ability, while NOTCH1 overexpression abrogated these effects. In addition, the GASC1 inhibitor caffeic acid and/or the NOTCH1 inhibitor DAPT (a γ­Secretase Inhibitor), efficiently suppressed the human glioma xenograft tumors. Thus, the present results demonstrated the importance of GASC1 in the progression of glioma and identified that GASC1 promotes glioma progression, at least in part, by enhancing NOTCH signaling, suggesting that GASC1/NOTCH1 signaling may be a potential therapeutic target for glioma treatment.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Receptor Notch1/metabolismo , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Ácidos Cafeicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Diaminas/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/tratamento farmacológico , Glioma/genética , Humanos , Histona Desmetilases com o Domínio Jumonji/antagonistas & inibidores , Histona Desmetilases com o Domínio Jumonji/genética , Masculino , Camundongos Nus , Interferência de RNA , Receptor Notch1/antagonistas & inibidores , Receptor Notch1/genética , Transdução de Sinais/genética , Tiazóis/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
19.
BMC Bioinformatics ; 22(1): 161, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765909

RESUMO

BACKGROUND: Cumulative evidence from biological experiments has confirmed that miRNAs have significant roles to diagnose and treat complex diseases. However, traditional medical experiments have limitations in time-consuming and high cost so that they fail to find the unconfirmed miRNA and disease interactions. Thus, discovering potential miRNA-disease associations will make a contribution to the decrease of the pathogenesis of diseases and benefit disease therapy. Although, existing methods using different computational algorithms have favorable performances to search for the potential miRNA-disease interactions. We still need to do some work to improve experimental results. RESULTS: We present a novel combined embedding model to predict MiRNA-disease associations (CEMDA) in this article. The combined embedding information of miRNA and disease is composed of pair embedding and node embedding. Compared with the previous heterogeneous network methods that are merely node-centric to simply compute the similarity of miRNA and disease, our method fuses pair embedding to pay more attention to capturing the features behind the relative information, which models the fine-grained pairwise relationship better than the previous case when each node only has a single embedding. First, we construct the heterogeneous network from supported miRNA-disease pairs, disease semantic similarity and miRNA functional similarity. Given by the above heterogeneous network, we find all the associated context paths of each confirmed miRNA and disease. Meta-paths are linked by nodes and then input to the gate recurrent unit (GRU) to directly learn more accurate similarity measures between miRNA and disease. Here, the multi-head attention mechanism is used to weight the hidden state of each meta-path, and the similarity information transmission mechanism in a meta-path of miRNA and disease is obtained through multiple network layers. Second, pair embedding of miRNA and disease is fed to the multi-layer perceptron (MLP), which focuses on more important segments in pairwise relationship. Finally, we combine meta-path based node embedding and pair embedding with the cost function to learn and predict miRNA-disease association. The source code and data sets that verify the results of our research are shown at https://github.com/liubailong/CEMDA . CONCLUSIONS: The performance of CEMDA in the leave-one-out cross validation and fivefold cross validation are 93.16% and 92.03%, respectively. It denotes that compared with other methods, CEMDA accomplishes superior performance. Three cases with lung cancers, breast cancers, prostate cancers and pancreatic cancers show that 48,50,50 and 50 out of the top 50 miRNAs, which are confirmed in HDMM V2.0. Thus, this further identifies the feasibility and effectiveness of our method.


Assuntos
Biologia Computacional , MicroRNAs , Redes Neurais de Computação , Algoritmos , Humanos , Masculino , MicroRNAs/genética , Software
20.
Cell Biol Int ; 45(7): 1393-1403, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33595160

RESUMO

Farnesyl pyrophosphate synthase (FPPS)-catalyzed isoprenoid intermediates are involved in diabetic cardiomyopathy. This study investigated the specific role of FPPS in the development of diabetic cardiomyopathy. We demonstrated that FPPS expression was elevated in both in vivo and in vitro models of diabetic cardiomyopathy. FPPS inhibition decreased the expression of proteins related to cardiac fibrosis and cardiomyocytic hypertrophy, including collagen I, collagen III, connective tissue growth factor, natriuretic factor, brain natriuretic peptide, and ß-myosin heavy chain. Furthermore, FPPS inhibition and knockdown prevented phosphorylated c-Jun N-terminal kinase 1/2 (JNK1/2) activation in vitro. In addition, a JNK1/2 inhibitor downregulated high-glucose-induced responses to diabetic cardiomyopathy. Finally, immunofluorescence revealed that cardiomyocytic size was elevated by high glucose and was decreased by zoledronate, small-interfering farnesyl pyrophosphate synthase (siFPPS), and a JNK1/2 inhibitor. Taken together, our findings indicate that FPPS and JNK1/2 may be part of a signaling pathway that plays an important role in diabetic cardiomyopathy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...