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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(1): 91-97, 2023 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-36655670

RESUMO

Neurodevelopmental disorders (NDDs) in children are a group of chronic developmental brain disorders caused by multiple genetic or acquired causes, including disorders of intellectual development, developmental speech or language disorders, autism spectrum disorders, developmental learning disorders, attention deficit hyperactivity disorder, tic disorders, and other neurodevelopmental disorders. With the improvement in the research level and the diagnosis and treatment techniques of NDDs, great progress has been made in the research on NDDs in children. This article reviews the research advances in NDDs, in order to further improve the breadth and depth of the understanding of NDDs in children among pediatricians.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Humanos , Criança , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/terapia , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/terapia
2.
Artigo em Inglês | MEDLINE | ID: mdl-36658682

RESUMO

AIM: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively kill tumor cells but has no significant effect on normal cells. However, the use of TRAIL is limited for resistance by more than 50% of the tumor cell lines. It's very important to develop a more efficient form of TRAIL for cancer treatment. METHODS: The N-terminal in soluble fragments (114-281aa) of TRAIL was redesigned to construct a novel TRAIL mutant-MuR5S4-TR. The Cell Counting Kit-8 method to explore the antitumor effects. The potential mechanisms were also explored. RESULTS: Novel TRAIL mutant with cell-penetrating peptides (CPP) like and Second mitochondria-derived activator of caspases (Smac) like structure-MuR5S4-TR was successfully constructed. The prokaryotic expression system was successfully built, and the MuR5S4-TR was purified and reconfirmed by western blot. MuR5S4-TR could enhance the antitumor effects of TRAIL in most of the cancer cell lines significantly, NCI-H460 lung cancer cell line, for instance. After MuR5S4-TR treatment, the expressions of death receptor 4 (DR4), DR5, Caspase-8, and cleaved Caspase-3 were remarkably increased, however, there was no significant difference in X-linked inhibitor of apoptosis expression. CONCLUSION: We constructed a novel TRAIL mutant with CPP-like and Smac-like structure-MuR5S4-TR. The MuR5S4-TR showed significantly stronger antitumor effects than TRAIL in many tumor cell lines. The MuR5S4-TR showed strong antitumor effects both in vitro and in vivo. This preliminary study implies that MuR5S4-TR may be a more efficient form of TRAIL for cancer therapy.

3.
Bioinformatics ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36661313

RESUMO

MOTIVATION: In single-cell transcriptomics applications, effective identification of cell types in multicellular organisms and in-depth study of the relationships between genes has become one of the main goals of bioinformatics research. However, data heterogeneity and random noise pose significant difficulties for scRNA-seq data analysis. RESULTS: We have proposed an adversarial dense graph convolutional network architecture for single-cell classification. Specifically, to enhance the representation of higher-order features and the organic combination between features, dense connectivity mechanism and attention-based feature aggregation are introduced for feature learning in convolutional neural networks. To preserve the features of the original data, we use a feature reconstruction module to assist the goal of single-cell classification. In addition, HNNVAT uses virtual adversarial training to improve the generalization and robustness. Experimental results show that our model outperforms the existing classical methods in terms of classification accuracy on benchmark datasets. AVAILABILITY: The source code of HNNVAT is available at https://github.com/DisscLab/HNNVAT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

4.
Can J Cardiol ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36669686

RESUMO

BACKGROUND: Mineralocorticoid receptor (MR) antagonists have been widely used to treat heart failure (HF). Studies have shown that MR in T cells plays important roles in hypertension and myocardial hypertrophy. However, the function of T cell MR in myocardial infarction (MI) has not been elucidated. METHODS: In this study, we used T cell MR knockout (TMRKO) mouse to investigate the impacts of T cell MR deficiency on MI and to explore the underlying mechanisms. Echocardiography and tissue staining were used to assess cardiac function, fibrosis, and myocardial apoptosis after MI. Flow cytometry and qRT-PCR were used to detect immune cell filtration and inflammation. RESULTS: T cell MR deficiency significantly improved cardiac function, promoted myocardial repair, and inhibited myocardial apoptosis, fibrosis and inflammation after MI. Luminex assays revealed that TMRKO mice had significantly lower levels of interferon-gamma and interleukin-6 (IL-6) in serum and infarcted myocardium than littermate control mice. In cultured splenic T cells, MR deficiency suppressed IL-6 expression whereas MR overexpression enhanced IL-6 expression. ChIP assay demonstrated that MR bound to the MR response element on the promoter of IL-6 gene. Finally, T cell MR deficiency significantly suppressed accumulation of macrophages in infarcted myocardium and differentiation of pro-inflammatory macrophages, thereby alleviating the consequences of MI. CONCLUSIONS: T cell MR deficiency improved pathological ventricular remodeling after MI, likely through inhibition of accumulation and differentiation of pro-inflammatory macrophages. At the molecular level, MR may work through interferon-gamma and IL-6 in T cells to exert functions in MI.

5.
BMC Cardiovasc Disord ; 23(1): 35, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658476

RESUMO

BACKGROUND: In recent years, heart failure with preserved ejection fraction (HFpEF) has received increasing clinical attention. To investigate the diagnostic value of diastolic function parameters derived from planar gated blood-pool imaging (MUGA) for detecting HFpEF in coronary atherosclerotic heart disease (coronary artery disease, CAD) patients. METHODS: Ninety-seven CAD patients with left ventricular ejection fraction ≥ 50% were included in the study. Based on the left ventricular end-diastolic pressure (LVEDP), the patients were divided into the HFpEF group (LVEDP ≥ 16 mmHg, 47 cases) and the normal LV diastolic function group (LVEDP < 16 mmHg, 50 cases). Diastolic function parameters obtained by planar MUGA include peak filling rate (PFR), filling fraction during the first third of diastole (1/3FF), filling rate during the first third of diastole (1/3FR), mean filling rate during diastole (MFR), and peak filling time (TPF). Echocardiographic parameters include left atrial volume index (LAVI), peak tricuspid regurgitation velocity (peak TR velocity), transmitral diastolic early peak inflow velocity (E), average early diastolic velocities of mitral annulars (average e'), average E/e' ratio. The diastolic function parameters obtained by planar MUGA were compared with those obtained by echocardiography to explore the clinical value of planar MUGA for detecting HFpEF. RESULTS: The Receiver-operating characteristic curve analysis of diastolic function parameters obtained from planar MUGA and echocardiography to detect HFpEF showed that: among the parameters examined by planar MUGA, the area under the curve (AUC) of PFR, 1/3FF, 1/3FR, MFR and TPF were 0.827, 0.662, 0.653, 0.663 and 0.809, respectively. Among the echocardiographic parameters, the AUCs for average e', average E/e' ratio, peak TR velocity, and LAVI values were 0.747, 0.706, 0.735, and 0.633. The combination of PFR and TPF showed an AUC of 0.856. PFR combined with TPF value demonstrated better predictive value than average e' (Z = 2.020, P = 0.043). CONCLUSION: Diastolic function parameters obtained by planar MUGA can be used to diagnose HFpEF in CAD patients. PFR combined with TPF was superior to the parameters obtained by echocardiography and showed good sensitivity and predictive power for detecting HFpEF.


Assuntos
Doença da Artéria Coronariana , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Função Ventricular Esquerda , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/diagnóstico por imagem , Imagem do Acúmulo Cardíaco de Comporta , Diástole
6.
J Transl Med ; 21(1): 48, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698208

RESUMO

BACKGROUND: Drug-target interaction (DTI) prediction has become a crucial prerequisite in drug design and drug discovery. However, the traditional biological experiment is time-consuming and expensive, as there are abundant complex interactions present in the large size of genomic and chemical spaces. For alleviating this phenomenon, plenty of computational methods are conducted to effectively complement biological experiments and narrow the search spaces into a preferred candidate domain. Whereas, most of the previous approaches cannot fully consider association behavior semantic information based on several schemas to represent complex the structure of heterogeneous biological networks. Additionally, the prediction of DTI based on single modalities cannot satisfy the demand for prediction accuracy. METHODS: We propose a multi-modal representation framework of 'DeepMPF' based on meta-path semantic analysis, which effectively utilizes heterogeneous information to predict DTI. Specifically, we first construct protein-drug-disease heterogeneous networks composed of three entities. Then the feature information is obtained under three views, containing sequence modality, heterogeneous structure modality and similarity modality. We proposed six representative schemas of meta-path to preserve the high-order nonlinear structure and catch hidden structural information of the heterogeneous network. Finally, DeepMPF generates highly representative comprehensive feature descriptors and calculates the probability of interaction through joint learning. RESULTS: To evaluate the predictive performance of DeepMPF, comparison experiments are conducted on four gold datasets. Our method can obtain competitive performance in all datasets. We also explore the influence of the different feature embedding dimensions, learning strategies and classification methods. Meaningfully, the drug repositioning experiments on COVID-19 and HIV demonstrate DeepMPF can be applied to solve problems in reality and help drug discovery. The further analysis of molecular docking experiments enhances the credibility of the drug candidates predicted by DeepMPF. CONCLUSIONS: All the results demonstrate the effectively predictive capability of DeepMPF for drug-target interactions. It can be utilized as a useful tool to prescreen the most potential drug candidates for the protein. The web server of the DeepMPF predictor is freely available at http://120.77.11.78/DeepMPF/ , which can help relevant researchers to further study.


Assuntos
COVID-19 , Aprendizado Profundo , Humanos , Simulação de Acoplamento Molecular , Semântica , Descoberta de Drogas/métodos , Proteínas
7.
Cell ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36693374

RESUMO

Downward social mobility is a well-known mental risk factor for depression, but its neural mechanism remains elusive. Here, by forcing mice to lose against their subordinates in a non-violent social contest, we lower their social ranks stably and induce depressive-like behaviors. These rank-decline-associated depressive-like behaviors can be reversed by regaining social status. In vivo fiber photometry and single-unit electrophysiological recording show that forced loss, but not natural loss, generates negative reward prediction error (RPE). Through the lateral hypothalamus, the RPE strongly activates the brain's anti-reward center, the lateral habenula (LHb). LHb activation inhibits the medial prefrontal cortex (mPFC) that controls social competitiveness and reinforces retreats in contests. These results reveal the core neural mechanisms mutually promoting social status loss and depressive behaviors. The intertwined neuronal signaling controlling mPFC and LHb activities provides a mechanistic foundation for the crosstalk between social mobility and psychological disorder, unveiling a promising target for intervention.

8.
J Diabetes Res ; 2023: 3786342, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643790

RESUMO

Background and Aims: Arterial stiffness and sarcopenia are commonly seen in patients with type 2 diabetes mellitus (T2DM), and both are age-related diseases. However, few studies have addressed the causal relationship between age, arterial stiffness, and sarcopenia, especially in patients with T2DM. This study is aimed at investigating the relationship among age, arterial stiffness, and sarcopenia in patients with T2DM. Methods and Results: This cross-sectional study enrolled 557 inpatients with diabetes at the First Affiliated Hospital of Wenzhou Medical University, China, between June 2020 and July 2021. Patients who were diagnosed with T2DM and underwent examination of dual-energy X-ray absorptiometry, handgrip strength, 6-meter walk speed, and brachial-ankle pulse wave velocity (baPWV, a recognized indicator of arterial stiffness) were enrolled. A total of 447 patients were included. A dose-dependent relationship was found between age and sarcopenia. We also found a dose-dependent relationship between age and baPWV. Similarly, significant dose-dependent relationships were found across baPWV tertiles with higher prevalence of sarcopenia. Then, a mediation analysis was performed to explore the mediation effect of arterial stiffness on age-associated sarcopenia. We found that the prevalence of sarcopenia increased by 0.0115 (95% CI, 0.0028-0.0239) per 1 year increase in age by the mediation effect of baPWV and that the direct effect of aging on sarcopenia was 0.0441 (95% CI, 0.0101-0.0909) per 1 year older. baPWV mediated 20.5% of the positive relationship between increased age and the prevalence of sarcopenia. Conclusions: Elevated baPWV partially mediates the association of age and sarcopenia among patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Sarcopenia , Rigidez Vascular , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Índice Tornozelo-Braço , Sarcopenia/epidemiologia , Fatores de Risco , Estudos Transversais , Força da Mão , Análise de Onda de Pulso , China/epidemiologia
9.
Commun Biol ; 6(1): 102, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702861

RESUMO

Protein acetylation plays a key role in regulating cellular processes and is subject to aberrant control in diverse pathologies. Although histone deacetylase (HDAC) inhibitors are approved drugs for certain cancers, it is not known whether they can be deployed in other therapeutic contexts. We have explored the clinical HDAC inhibitor, zabadinostat/CXD101, and found that it is a stand-alone regulator of the adaptive immune response. Zabadinostat treatment increased expression of MHC class I and II genes in a variety of cells, including dendritic cells (DCs) and healthy tissue. Remarkably, zabadinostat enhanced the activity of DCs, and CD4 and CD8 T lymphocytes. Using an antigenic peptide presented to the immune system by MHC class I, zabadinostat caused an increase in antigen-specific CD8 T lymphocytes. Further, mice immunised with covid19 spike protein and treated with zabadinostat exhibit enhanced covid19 neutralising antibodies and an increased level of T lymphocytes. The enhanced humoral response reflected increased activity of T follicular helper (Tfh) cells and germinal centre (GC) B cells. Our results argue strongly that zabadinostat has potential to augment diverse therapeutic agents that act through the immune system.


Assuntos
COVID-19 , Imunidade Humoral , Camundongos , Animais , Linfócitos T Auxiliares-Indutores , Inibidores de Histona Desacetilases/farmacologia , Imunidade Adaptativa , Antígenos
10.
Adv Radiat Oncol ; 8(1): 101126, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36711063

RESUMO

Purpose: Our purpose was to examine outcomes of patients with locally advanced endometrial cancer who undergo neoadjuvant chemotherapy followed by surgery (PreCT) with/without postoperative adjuvant radiation therapy. A secondary analysis of down staging and margin clearance was made with reference to those receiving upfront surgery and then adjuvant chemotherapy (PostCT). Methods and Materials: The National Cancer Database was queried for FIGO (The International Federation of Gynecology and Obstetrics) stage III/IV locally advanced endometrial cancer cases who underwent definitive surgery from 2010 to 2016 and received chemotherapy as part of their treatment. Cases were classified into 2 cohorts: preoperative chemotherapy +/- postoperative chemotherapy cohort (PreCT) and postoperative chemotherapy cohort (PostCT) for reference for margin assessment. Cases who received preoperative radiation therapy were excluded while those who received postoperative radiation were included in the analysis. Primary endpoints were overall survival (OS), surgical margin status, rate of downstaging, and effect of adjuvant radiation therapy on OS among the PreCT cohort. Univariable (UVA) and multivariable (MVA) Cox regression analyses were performed. Results: A total of 13,369 cases were identified with 1059 in PreCT and 12,310 in PostCT cohorts. PreCT had lower OS than PostCT (UVA: hazard ratio [HR], 2.18; P < .001; MVA: HR, 1.873; P < .001). PreCT cases with negative margins, who presumably had unresectable tumors initially, also had worse OS compared with PostCT with negative margins (UVA: HR, 2.20; P < .001; MVA: HR, 1.84; P < .001); however, PreCT with negative margins had similar survival to PostCT with positive margins (UVA: HR, 0.825; P < .001; MVA: P = .885). The addition of radiation after surgery in the PreCT cohort was associated with improved survival (5-year OS 20.5% compared with 50%, respectively; UVA: HR, 0.450; P < .001; MVA: HR, 0.337; P < .001). Although fewer cases in PreCT had negative margins compared with PostCT (72% compared with 84%, P < .001), approximately 19% of cases in PreCT had lower pathologic T-stage compared with clinical T-stage and 11% had lower N-stage. Conclusions: Neoadjuvant chemotherapy was given in cases with worse oncologic prognostic factors, many of whom were likely unresectable at outset, compared with those who received postoperative chemotherapy. Although neoadjuvant chemotherapy is associated with tumor downstaging, survival is lower than with primary surgery probably because of these baseline differences. The addition of adjuvant radiation after surgery in cases who received preoperative chemotherapy is associated with improved survival.

11.
Eur J Med Chem ; 246: 115009, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36527933

RESUMO

SMYD3 is a histone methyltransferase involved in transcriptional regulation, and its overexpression in various forms of cancer justifies that blocking SMYD3 functions can serve as a novel therapeutic strategy in cancer treatment. Herein, a series of novel tetrahydrofuranyl spirooxindoles were designed and synthesized based on a structure-based drug design strategy. Subsequent biochemical analysis suggested that these novel SMYD3 inhibitors showed good anticancer activity against stomach adenocarcinoma both in vitro and in vivo. Among them, compound 7r exhibited potent inhibitory capacities against SMYD3 and BGC823 cells with IC50 values of 0.81 and 0.75 µM, respectively. Mechanistic investigations showed that 7r could suppress Akt methylation and activation by SMYD3 and trigger lethal autophagic flux inhibition via the Akt-mTOR pathway. Collectively, our results may bridge the rational discovery of privileged structures, epigenetic targeting of SMYD3, and regulation of autophagic cell death.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Processamento de Proteína Pós-Traducional , Autofagia , Linhagem Celular Tumoral , Histona-Lisina N-Metiltransferase/metabolismo
12.
J Adv Res ; 43: 147-161, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36585105

RESUMO

INTRODUCTION: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered. OBJECTIVES: To characterize the alterations of oral and gut microbiota and their roles in HTN. METHODS: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN. RESULTS: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition. CONCLUSIONS: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.


Assuntos
Microbioma Gastrointestinal , Hipertensão , Microbiota , Periodontite , Humanos , Animais , Camundongos , Microbioma Gastrointestinal/fisiologia , RNA Ribossômico 16S/genética , Estudos Transversais , Seguimentos , Camundongos Endogâmicos C57BL
13.
BJOG ; 130(2): 222-230, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36056595

RESUMO

OBJECTIVE: We evaluated whether radiomic features extracted from planning computed tomography (CT) scans predict clinical end points in patients with locally advanced cervical cancer (LACC) undergoing intensity-modulated radiation therapy and brachytherapy. DESIGN: A retrospective cohort study. SETTING: Xiangya Hospital of Central South University, Changsha, Hunan, China. POPULATION: Two hundred and fifty-seven LACC patients who were treated with intensity-modulated radiotherapy from 2014 to 2017. METHODS: Patients were allocated into the training/validation sets (3:1 ratio) using proportional random sampling, resulting in the same proportion of groups in the two sets. We extracted 254 radiomic features from each of the gross target volume, pelvis and sacral vertebrae. The sequentially backward elimination support vector machine algorithm was used for feature selection and end point prediction. MAIN OUTCOMES AND MEASURES: Clinical end points include tumour complete response (CR), 5-year overall survival (OS), anaemia, and leucopenia. RESULTS: A combination of ten clinicopathological parameters and 34 radiomic features performed best for predicting CR (validation balanced accuracy: 80.8%). The validation balanced accuracy of 54 radiomic features was 85.8% for OS, and their scores can stratify patients into the low-risk and high-risk groups (5-year OS: 95.5% versus 36.4%, p < 0.001). The clinical and radiomic models were also predictive of anaemia and leucopenia (validation balanced accuracies: 71.0% and 69.9%). CONCLUSION: This study demonstrated that combining clinicopathological parameters with CT-based radiomics may have value for predicting clinical end points in LACC. If validated, this model may guide therapeutic strategy to optimise the effectiveness and minimise toxicity or treatment for LACC.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Pelve
14.
Biomater Adv ; 145: 213252, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36563510

RESUMO

To obtain multifunctional materials suitable for guiding alveolar bone regeneration under infectious conditions, we prepared asymmetric membranes comprising space acquiring layer that involves fibroblast inhibitor poly(p-dioxanone-co-L-phenylalanine) (PDPA), an isolating dense layer that forms barrier between two layers and an osteogenesis inducing electrospinning layer which involves hydroxyapatite or hydroxyapatite & minocycline. Then the composition, crystallization, morphology, and hydrophilicity of asymmetric membranes were analyzed. Minocycline incorporated membranes controlled the expansion of Porphyromonas gingivalis (P. gingivalis) in vitro. Hydroxyapatite-incorporated asymmetric membranes promoted the expression of osteogenesis related genes RUNX2, OPN, ALP of MC3T3-E1 cells in vitro. The mineralization of MC3T3-E1 cells cultured with hydroxyapatite-incorporated asymmetric membranes were also promoted in vitro. Asymmetric membranes especially hydroxyapatite-incorporated ones guided the regeneration of the mandibular bone defect in vivo. Bone regeneration guided under infectious conditions was evaluated in a P. gingivalis infected alveolar bone defect model. Specifically, space acquiring layer containing asymmetric membranes effectively controlled connective tissue hyperplasia at defect sites. The excellent guided bone regeneration achieved by applying a single space acquiring layer membrane further indicates the importance of acquiring space actively to induce bone regeneration. Hydroxyapatite-minocycline incorporated symmetric membranes could simultaneously suppress alveolar bone reabsorption caused by infection and guide regeneration of defects. Therefore, the hydroxyapatite-minocycline incorporated asymmetric membrane may be more suitable to be applied in guiding regeneration of bone defects under complex infectious conditions.


Assuntos
Membranas Artificiais , Minociclina , Regeneração Óssea , Durapatita/química , Durapatita/farmacologia , Minociclina/farmacologia , Osteogênese , Animais , Camundongos
15.
Neural Regen Res ; 18(6): 1347-1353, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36453422

RESUMO

Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer's disease mouse models and patients, and that it plays a vital role in the learning and memory. However, the underlying mechanisms of fibroblast growth factor 13 in Alzheimer's disease remain unclear. In this study, we established rat models of Alzheimer's disease by stereotaxic injection of amyloid-ß (Aß1-42)-induced into bilateral hippocampus. We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13. The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer's disease model rats. After overexpression of fibroblast growth factor 13, learning and memory abilities of the Alzheimer's disease model rats were remarkably improved. Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione, superoxide dismutase, phosphatidylinositol-3-kinase, AKT and glycogen synthase kinase 3ß, and anti-apoptotic factor BCL. Furthermore, fibroblast growth factor 13 overexpression decreased the number of apoptotic cells, expression of pro-apoptotic factor BAX, cleaved-caspase 3 and amyloid-ß expression, and levels of tau phosphorylation, malondialdehyde, reactive oxygen species and acetylcholinesterase in the brain of Alzheimer's disease model rats. The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer's disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3ß signaling pathway.

16.
Comput Med Imaging Graph ; 103: 102150, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36493595

RESUMO

Magnetic resonance (MR) image-guided radiation therapy is a hot topic in current radiation therapy research, which relies on MR to generate synthetic computed tomography (SCT) images for radiation therapy. Convolution-based generative adversarial networks (GAN) have achieved promising results in synthesizing CT from MR since the introduction of deep learning techniques. However, due to the local limitations of pure convolutional neural networks (CNN) structure and the local mismatch between paired MR and CT images, particularly in pelvic soft tissue, the performance of GAN in synthesizing CT from MR requires further improvement. In this paper, we propose a new GAN called Residual Transformer Conditional GAN (RTCGAN), which exploits the advantages of CNN in local texture details and Transformer in global correlation to extract multi-level features from MR and CT images. Furthermore, the feature reconstruction loss is used to further constrain the image potential features, reducing over-smoothing and local distortion of the SCT. The experiments show that RTCGAN is visually closer to the reference CT (RCT) image and achieves desirable results on local mismatch tissues. In the quantitative evaluation, the MAE, SSIM, and PSNR of RTCGAN are 45.05 HU, 0.9105, and 28.31 dB, respectively. All of them outperform other comparison methods, such as deep convolutional neural networks (DCNN), Pix2Pix, Attention-UNet, WPD-DAGAN, and HDL.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Tomografia Computadorizada por Raios X , Espectroscopia de Ressonância Magnética
17.
Food Funct ; 14(1): 74-86, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36504256

RESUMO

In this work, we investigated the ameliorative effects of platycodin D (PD), a major active chemical ingredient isolated from the roots of Platycodon grandiflorum (PG), on high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes (T2D) mice. PD treatment (2.5 and 5.0 mg kg-1) improved HFD-induced body weight gain. PD administration also decreased the fasting blood glucose (FBG) level and improved glucose and insulin tolerance levels. These data collectively showed that PD could maintain glucose homeostasis. In addition, the diabetic mice with PD treatment also showed fewer pathological changes in liver tissues and improved hepatic functional indexes with respect to the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and recovery of abnormal liver function caused by T2D. Except for these, PD decreased the decomposition of hepatic glycogen. The results from western blot analysis showed that PD treatment might regulate the hepatic gluconeogenesis pathway with the increased phosphorylation/expression of AMPK and decreased expressions of PCK1 and G6Pase. In the aspect of lipid metabolism, PD decreased the whole-body lipid levels, including total cholesterol (TC), triglycerides (TG), and high-density lipoprotein (HDL), and reduced the hepatic fat accumulation induced by T2D through the AMPK/ACC/CPT-1 fatty acid anabolism pathway. In addition, the results of molecular docking showed that PD may have a potential direct effect on AMPK and other key glycolipid metabolism proteins. To summarize, PD modulation of hepatic glycolipid metabolism abnormalities is promising for T2D therapy in the future.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hiperglicemia , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Glucose/metabolismo , Hiperglicemia/metabolismo , Fígado/metabolismo , Simulação de Acoplamento Molecular , Estreptozocina
18.
BMC Bioinformatics ; 23(Suppl 7): 518, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457083

RESUMO

BACKGROUND: Self-interacting proteins (SIPs), two or more copies of the protein that can interact with each other expressed by one gene, play a central role in the regulation of most living cells and cellular functions. Although numerous SIPs data can be provided by using high-throughput experimental techniques, there are still several shortcomings such as in time-consuming, costly, inefficient, and inherently high in false-positive rates, for the experimental identification of SIPs even nowadays. Therefore, it is more and more significant how to develop efficient and accurate automatic approaches as a supplement of experimental methods for assisting and accelerating the study of predicting SIPs from protein sequence information. RESULTS: In this paper, we present a novel framework, termed GLCM-WSRC (gray level co-occurrence matrix-weighted sparse representation based classification), for predicting SIPs automatically based on protein evolutionary information from protein primary sequences. More specifically, we firstly convert the protein sequence into Position Specific Scoring Matrix (PSSM) containing protein sequence evolutionary information, exploiting the Position Specific Iterated BLAST (PSI-BLAST) tool. Secondly, using an efficient feature extraction approach, i.e., GLCM, we extract abstract salient and invariant feature vectors from the PSSM, and then perform a pre-processing operation, the adaptive synthetic (ADASYN) technique, to balance the SIPs dataset to generate new feature vectors for classification. Finally, we employ an efficient and reliable WSRC model to identify SIPs according to the known information of self-interacting and non-interacting proteins. CONCLUSIONS: Extensive experimental results show that the proposed approach exhibits high prediction performance with 98.10% accuracy on the yeast dataset, and 91.51% accuracy on the human dataset, which further reveals that the proposed model could be a useful tool for large-scale self-interacting protein prediction and other bioinformatics tasks detection in the future.


Assuntos
Evolução Biológica , Biologia Computacional , Humanos , Sequência de Aminoácidos , Matrizes de Pontuação de Posição Específica , Leucócitos , Saccharomyces cerevisiae/genética
19.
Cell Death Dis ; 13(12): 1020, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470869

RESUMO

Doxorubicin (DOX) is an effective anthracycline chemotherapeutic anticancer drug with its life-threatening cardiotoxicity severely limiting its clinical application. Mitochondrial damage-induced cardiomyocyte death is considered an essential cue for DOX cardiotoxicity. FUN14 domain containing 1 (FUNDC1) is a mitochondrial membrane protein participating in the regulation of mitochondrial integrity in multiple diseases although its role in DOX cardiomyopathy remains elusive. Here, we examined whether PANoptosis, a novel type of programmed cell death closely associated with mitochondrial damage, was involved in DOX-induced heart injury, and FUNDC1-mediated regulation of cardiomyocyte PANoptosis, if any. FUNDC1 was downregulated in heart tissues in patients with dilated cardiomyopathy (DCM) and DOX-challenged mice. FUNDC1 deficiency aggravated DOX-induced cardiac dysfunction, mitochondrial injury, and cardiomyocyte PANoptosis. Further examination revealed that FUNDC1 countered cytoplasmic release of mitochondrial DNA (mtDNA) and activation of PANoptosome through interaction with mitochondrial Tu translation elongation factor (TUFM), a key factor in the translational expression and repair of mitochondrial DNA, via its 96-133 amino acid domain. TUFM intervention reversed FUNDC1-elicited protection against DOX-induced mtDNA cytosolic release and cardiomyocyte PANoptosis. Our findings shed light toward a beneficial role of FUNDC1 in DOX cardiotoxicity and cardiomyocyte PANoptosis, thus offering therapeutic promises in DOX-induced cardiotoxicity.


Assuntos
Cardiotoxicidade , Miócitos Cardíacos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Cardiotoxicidade/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Mitocôndrias/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/metabolismo , Apoptose , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo
20.
J Transl Med ; 20(1): 552, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463215

RESUMO

BACKGROUND: Associations of drugs with diseases provide important information for expediting drug development. Due to the number of known drug-disease associations is still insufficient, and considering that inferring associations between them through traditional in vitro experiments is time-consuming and costly. Therefore, more accurate and reliable computational methods urgent need to be developed to predict potential associations of drugs with diseases. METHODS: In this study, we present the model called weighted graph regularized collaborative non-negative matrix factorization for drug-disease association prediction (WNMFDDA). More specifically, we first calculated the drug similarity and disease similarity based on the chemical structures of drugs and medical description information of diseases, respectively. Then, to extend the model to work for new drugs and diseases, weighted [Formula: see text] nearest neighbor was used as a preprocessing step to reconstruct the interaction score profiles of drugs with diseases. Finally, a graph regularized non-negative matrix factorization model was used to identify potential associations between drug and disease. RESULTS: During the cross-validation process, WNMFDDA achieved the AUC values of 0.939 and 0.952 on Fdataset and Cdataset under ten-fold cross validation, respectively, which outperforms other competing prediction methods. Moreover, case studies for several drugs and diseases were carried out to further verify the predictive performance of WNMFDDA. As a result, 13(Doxorubicin), 13(Amiodarone), 12(Obesity) and 12(Asthma) of the top 15 corresponding candidate diseases or drugs were confirmed by existing databases. CONCLUSIONS: The experimental results adequately demonstrated that WNMFDDA is a very effective method for drug-disease association prediction. We believe that WNMFDDA is helpful for relevant biomedical researchers in follow-up studies.


Assuntos
Algoritmos , Asma , Humanos , Análise por Conglomerados , Bases de Dados Factuais , Projetos de Pesquisa
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