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1.
IEEE Trans Med Imaging ; PP2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801690

RESUMO

It is an essential task to accurately diagnose cancer subtypes in computational pathology for personalized cancer treatment. Recent studies have indicated that the combination of multimodal data, such as whole slide images (WSIs) and multi-omics data, could achieve more accurate diagnosis. However, robust cancer diagnosis remains challenging due to the heterogeneity among multimodal data, as well as the performance degradation caused by insufficient multimodal patient data. In this work, we propose a novel multimodal co-attention fusion network (MCFN) with online data augmentation (ODA) for cancer subtype classification. Specifically, a multimodal mutual-guided co-attention (MMC) module is proposed to effectively perform dense multimodal interactions. It enables multimodal data to mutually guide and calibrate each other during the integration process to alleviate inter- and intra-modal heterogeneities. Subsequently, a self-normalizing network (SNN)-Mixer is developed to allow information communication among different omics data and alleviate the high-dimensional small-sample size problem in multi-omics data. Most importantly, to compensate for insufficient multimodal samples for model training, we propose an ODA module in MCFN. The ODA module leverages the multimodal knowledge to guide the data augmentations of WSIs and maximize the data diversity during model training. Extensive experiments are conducted on the public TCGA dataset. The experimental results demonstrate that the proposed MCFN outperforms all the compared algorithms, suggesting its effectiveness.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38630567

RESUMO

The B-mode ultrasound based computer-aided diagnosis (CAD) has demonstrated its effectiveness for diagnosis of Developmental Dysplasia of the Hip (DDH) in infants, which can conduct the Graf's method by detecting landmarks in hip ultrasound images. However, it is still necessary to explore more valuable information around these landmarks to enhance feature representation for improving detection performance in the detection model. To this end, a novel Involution Transformer based U-Net (IT-UNet) network is proposed for hip landmark detection. The IT-UNet integrates the efficient involution operation into Transformer to develop an Involution Transformer module (ITM), which consists of an involution attention block and a squeeze-and-excitation involution block. The ITM can capture both the spatial-related information and long-range dependencies from hip ultrasound images to effectively improve feature representation. Moreover, an Involution Downsampling block (IDB) is developed to alleviate the issue of feature loss in the encoder modules, which combines involution and convolution for the purpose of downsampling. The experimental results on two DDH ultrasound datasets indicate that the proposed IT-UNet achieves the best landmark detection performance, indicating its potential applications.

3.
IEEE Trans Med Imaging ; 43(7): 2509-2521, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38373131

RESUMO

Deep learning (DL) has proven highly effective for ultrasound-based computer-aided diagnosis (CAD) of breast cancers. In an automatic CAD system, lesion detection is critical for the following diagnosis. However, existing DL-based methods generally require voluminous manually-annotated region of interest (ROI) labels and class labels to train both the lesion detection and diagnosis models. In clinical practice, the ROI labels, i.e. ground truths, may not always be optimal for the classification task due to individual experience of sonologists, resulting in the issue of coarse annotation to limit the diagnosis performance of a CAD model. To address this issue, a novel Two-Stage Detection and Diagnosis Network (TSDDNet) is proposed based on weakly supervised learning to improve diagnostic accuracy of the ultrasound-based CAD for breast cancers. In particular, all the initial ROI-level labels are considered as coarse annotations before model training. In the first training stage, a candidate selection mechanism is then designed to refine manual ROIs in the fully annotated images and generate accurate pseudo-ROIs for the partially annotated images under the guidance of class labels. The training set is updated with more accurate ROI labels for the second training stage. A fusion network is developed to integrate detection network and classification network into a unified end-to-end framework as the final CAD model in the second training stage. A self-distillation strategy is designed on this model for joint optimization to further improves its diagnosis performance. The proposed TSDDNet is evaluated on three B-mode ultrasound datasets, and the experimental results indicate that it achieves the best performance on both lesion detection and diagnosis tasks, suggesting promising application potential.


Assuntos
Neoplasias da Mama , Interpretação de Imagem Assistida por Computador , Aprendizado de Máquina Supervisionado , Ultrassonografia Mamária , Humanos , Neoplasias da Mama/diagnóstico por imagem , Feminino , Interpretação de Imagem Assistida por Computador/métodos , Ultrassonografia Mamária/métodos , Aprendizado Profundo , Algoritmos , Mama/diagnóstico por imagem
4.
IEEE Trans Med Imaging ; 43(3): 902-915, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37815963

RESUMO

Computer-aided diagnosis (CAD) can help pathologists improve diagnostic accuracy together with consistency and repeatability for cancers. However, the CAD models trained with the histopathological images only from a single center (hospital) generally suffer from the generalization problem due to the straining inconsistencies among different centers. In this work, we propose a pseudo-data based self-supervised federated learning (FL) framework, named SSL-FT-BT, to improve both the diagnostic accuracy and generalization of CAD models. Specifically, the pseudo histopathological images are generated from each center, which contain both inherent and specific properties corresponding to the real images in this center, but do not include the privacy information. These pseudo images are then shared in the central server for self-supervised learning (SSL) to pre-train the backbone of global mode. A multi-task SSL is then designed to effectively learn both the center-specific information and common inherent representation according to the data characteristics. Moreover, a novel Barlow Twins based FL (FL-BT) algorithm is proposed to improve the local training for the CAD models in each center by conducting model contrastive learning, which benefits the optimization of the global model in the FL procedure. The experimental results on four public histopathological image datasets indicate the effectiveness of the proposed SSL-FL-BT on both diagnostic accuracy and generalization.


Assuntos
Algoritmos , Diagnóstico por Computador
5.
Org Lett ; 25(49): 8792-8796, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38059767

RESUMO

A heterobifunctional cross-linker with one sulfhydryl-reactive dinitroimidazole end and another amine-reactive N-hydroxysuccinimide (NHS) ester end was designed and synthesized. The two motifs of this cross-linker, dinitroimidazole and NHS ester, proved to react with thiol and amine, respectively, in an orthogonal way. The cross-linker was further applied to construct stapled peptides of different sizes and mono- and dual functionalization (including biotinylation, PEGylation, and fluorescence labeling) of protein.


Assuntos
Cisteína , Lisina , Nitroimidazóis , Peptídeos , Aminas , Reagentes de Ligações Cruzadas , Imidazóis/química , Peptídeos/química , Proteínas , Compostos de Sulfidrila , Nitroimidazóis/química
6.
Front Oncol ; 13: 1248830, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869091

RESUMO

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid malignancy and also has an excellent prognosis. Primary thyroid lymphoma (PTL) is rare and has a poor prognosis. The co-occurrence of both malignancies is extremely rare, and the preoperative diagnosis is rather difficult. We report the case of a patient with both PTC and PTL in the setting of Hashimoto's thyroiditis (HT). A 59-year-old female patient was referred to our department for progressive enlargement of the thyroid gland over a few months. The imaging results demonstrated an enlarged thyroid and a mass in the thyroid. Total thyroidectomy and bilateral central neck node dissection were conducted. The final diagnosis of the coexistence of thyroid diffuse large B cell lymphoma and PTC was confirmed by histopathology and immunohistochemistry. The patient received radiation therapy and six cycles of chemotherapy combined with targeted therapy, including rituximab, cyclophosphamide, doxorubicin, vindesine, and prednisone (R-CHOP). After 6 months of follow-up, neither tumor has recurred. It is important for physicians to keep PTL in mind for differential diagnosis in HT patients with sudden thyroid enlargement.

7.
IEEE J Biomed Health Inform ; 27(12): 5926-5936, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37725722

RESUMO

The multi-scale information among the whole slide images (WSIs) is essential for cancer diagnosis. Although the existing multi-scale vision Transformer has shown its effectiveness for learning multi-scale image representation, it still cannot work well on the gigapixel WSIs due to their extremely large image sizes. To this end, we propose a novel Multi-scale Efficient Graph-Transformer (MEGT) framework for WSI classification. The key idea of MEGT is to adopt two independent efficient Graph-based Transformer (EGT) branches to process the low-resolution and high-resolution patch embeddings (i.e., tokens in a Transformer) of WSIs, respectively, and then fuse these tokens via a multi-scale feature fusion module (MFFM). Specifically, we design an EGT to efficiently learn the local-global information of patch tokens, which integrates the graph representation into Transformer to capture spatial-related information of WSIs. Meanwhile, we propose a novel MFFM to alleviate the semantic gap among different resolution patches during feature fusion, which creates a non-patch token for each branch as an agent to exchange information with another branch by cross-attention mechanism. In addition, to expedite network training, a new token pruning module is developed in EGT to reduce the redundant tokens. Extensive experiments on both TCGA-RCC and CAMELYON16 datasets demonstrate the effectiveness of the proposed MEGT.


Assuntos
Fontes de Energia Elétrica , Semântica , Humanos
8.
Nat Commun ; 14(1): 2586, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142563

RESUMO

Glioblastoma (GBM) diffusely infiltrates the brain and intermingles with non-neoplastic brain cells, including astrocytes, neurons and microglia/myeloid cells. This complex mixture of cell types forms the biological context for therapeutic response and tumor recurrence. We used single-nucleus RNA sequencing and spatial transcriptomics to determine the cellular composition and transcriptional states in primary and recurrent glioma and identified three compositional 'tissue-states' defined by cohabitation patterns between specific subpopulations of neoplastic and non-neoplastic brain cells. These tissue-states correlated with radiographic, histopathologic, and prognostic features and were enriched in distinct metabolic pathways. Fatty acid biosynthesis was enriched in the tissue-state defined by the cohabitation of astrocyte-like/mesenchymal glioma cells, reactive astrocytes, and macrophages, and was associated with recurrent GBM and shorter survival. Treating acute slices of GBM with a fatty acid synthesis inhibitor depleted the transcriptional signature of this pernicious tissue-state. These findings point to therapies that target interdependencies in the GBM microenvironment.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/patologia , Prognóstico , Neoplasias Encefálicas/patologia , Glioma/genética , Astrócitos/metabolismo , Microambiente Tumoral/genética
9.
Environ Res ; 227: 115721, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36965788

RESUMO

The abnormal progression of tumors has been a problem for treatment of cancer and therapeutic should be directed towards targeting main mechanisms involved in tumorigenesis in tumors. The genomic mutations can result in changes in biological mechanisms in human cancers. Colorectal cancer is one of the most malignant tumors of gastrointestinal tract and its treatment has been faced some difficulties due to development of resistance in tumor cells and also, their malignant behavior. Hence, new therapeutic modalities for colorectal cancer are being investigated. Autophagy is a "self-digestion" mechanism that is responsible for homeostasis preserving in cells and its aberrant activation/inhibition can lead to tumorigenesis. The current review focuses on the role of autophagy mechanism in colorectal cancer. Autophagy may be associated with increase/decrease in progression of colorectal cancer due to mutual function of this molecular mechanism. Pro-survival autophagy inhibits apoptosis to increase proliferation and survival rate of colorectal tumor cells and it is also involved in cancer metastasis maybe due to EMT induction. In contrast, pro-death autophagy decreases growth and invasion of colorectal tumor cells. The status of autophagy (upregulation and down-regulation) is a determining factor for therapy response in colorectal tumor cells. Therefore, targeting autophagy can increase sensitivity of colorectal tumor cells to chemotherapy and radiotherapy. Interestingly, nanoparticles can be employed for targeting autophagy in cancer therapy and they can both induce/suppress autophagy in tumor cells. Furthermore, autophagy modulators can be embedded in nanostructures in improving tumor suppression and providing cancer immunotherapy.


Assuntos
Autofagia , Neoplasias Colorretais , Humanos , Autofagia/genética , Apoptose , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular Tumoral , Carcinogênese
10.
Wounds ; 35(3): E107-E112, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36927739

RESUMO

INTRODUCTION: MU is an aggressive entity, and extended surgical resection is the primary treatment. The defects from an MU extended resection need repair using free flaps, of which the ALT free flap is the most common. OBJECTIVE: This study described the feasibility and application value of the ALT free flap in repairing defects after MU resection. MATERIALS AND METHODS: Fifteen patients with MU had repairs with ALT free flaps and were treated by the authors' unit from June 2015 through June 2021. All defects were repaired with 1 ALT free flap except for 1 case that required 2 flaps. RESULTS: The average age of the 11 male and 4 female patients was 52 years (range, 36-71 years). Defect sizes ranged from 8 cm × 5.5 cm to 21 cm × 13.5 cm (mean size, 10.9 cm × 6.5 cm). Flap sizes ranged from 10 cm × 7.5 cm to 23 cm × 15.5 cm (mean size, 12.9 cm × 8.5 cm). All flaps survived completely except for 1 flap in which re-exploration was needed. CONCLUSIONS: The individualized ALT free flap may be selected based on the receiving area characteristics and has certain clinical application value in defect repair after MU resection.


Assuntos
Retalhos de Tecido Biológico , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Retalhos de Tecido Biológico/cirurgia , Transplante de Pele , Estudos Retrospectivos , Úlcera , Resultado do Tratamento , Lesões dos Tecidos Moles/cirurgia
11.
Clin Transl Oncol ; 25(8): 2408-2418, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36848028

RESUMO

BACKGROUND: Osteosarcoma is a malignant tumor that can present with pain in the bones, joints, and local masses. The incidence is highest in adolescents, and the most common sites are the distal femur, proximal tibia and proximal humerus metaphyseal. Doxorubicin is the first-line chemotherapeutic agent for the treatment of osteosarcoma, but it has many side effects. Cannabidiol is a non-psychoactive plant cannabinoid cannabinol (CBD) that has been shown to be effective against osteosarcoma; however, the molecular targets and mechanisms of CBD action in osteosarcoma remain unclear. METHODS: Cell proliferation, migration, invasion and colony formation were analyzed using two drugs alone or in combination to evaluate their inhibitory effects on the malignant characteristics of OS cells. Apoptosis and the cell cycle were detected by flow cytometry. The synergistic inhibitory effect of doxorubicin/cannabidiol on tumors was also detected in nude mouse xenotransplantation models. RESULTS: Through analysis of two osteosarcoma cell lines, MG63 and U2R, it was found that the cannabidiol/doxorubicin combination treatment synergistically inhibited growth, migration and invasion and induced apoptosis, blocking G2 stagnation in OS cells. Further mechanistic exploration suggests that the PI3K-AKT-mTOR pathway and MAPK pathway play an important role in the synergistic inhibitory effect of the two drugs in osteosarcoma. Finally, in vivo experimental results showed that the cannabidiol/doxorubicin combination treatment significantly reduced the number of tumor xenografts compared to cannabidiol alone or doxorubicin alone. CONCLUSIONS: Our findings in this study suggest that cannabidiol and doxorubicin have a synergistic anticancer effect on OS cells, and their combined application may be a promising treatment strategy for OS.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Canabidiol , Osteossarcoma , Animais , Camundongos , Humanos , Antineoplásicos/uso terapêutico , Fosfatidilinositol 3-Quinases , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Osteossarcoma/metabolismo , Apoptose , Neoplasias Ósseas/patologia , Proliferação de Células
12.
RSC Adv ; 12(49): 31629-31638, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36380964

RESUMO

A series of polylactic acid (PLA)/polyethylene glycol (PEG) blends was prepared by melt blending using PEG as a plasticizer to address the disadvantages of PLA brittleness. PEG can weaken the intermolecular chain interactions of PLA and improve its processing properties. PLA-grafted maleic anhydride (GPLA) was reactively blended with PLA/PEG to obtain a high tenacity PLA/PEG/GPLA blend. GPLA was prepared by melt grafting using diisopropyl peroxide as the initiator and maleic anhydride as the graft. The effects of different PEG molecular weights (1000-10 000 g mol-1) on the properties of PLA/PEG/GPLA blends were investigated. GPLA reacted with PEG1000 (M w = 1000 g mol-1) to form short PLA branched chains and reacted with PEG10000 (M w = 10 000 g mol-1) to form a small number of PLA branched chains, which was unconducive to increasing the intermolecular chain entanglement. The branched PLA formed by the reaction between PEG6000 (M w = 6000 g mol-1) and GPLA had a remarkable effect on increasing intermolecular chain entanglement. The complex viscosity, modulus, and melt strength values of PLA/PEG6000/GPLA blends were relatively large. The elongation at break of the blends reached 526.9%, and the tensile strength was 30.91 MPa. It provides an effective way to prepare PLA materials with excellent comprehensive properties.

13.
Front Immunol ; 13: 982278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263050

RESUMO

Excessive subchondral angiogenesis is a key pathological feature of osteoarthritis (OA), as it alters the balance of subchondral bone remodeling and causes progressive cartilage degradation. We previously found that miR-210-3p correlates negatively with angiogenesis, though the specific mechanism of miR-210-3p-related angiogenesis in subchondral bone during OA progression remains unclear. This study was conducted to identify the miR-210-3p-modulating subchondral angiogenesis mechanism in OA and investigate its therapeutic effect. We found that miR-210-3p expression correlated negatively with subchondral endomucin positive (Emcn+) vasculature in the knee joints of OA mice. miR-210-3p overexpression regulated the angiogenic ability of endothelial cells (ECs) under hypoxic conditions in vitro. Mechanistically, miR-210-3p inhibited ECs angiogenesis by suppressing transforming growth factor beta receptor 1 (TGFBR1) mRNA translation and degrading DNA-binding inhibitor 4 (ID4) mRNA. In addition, TGFBR1 downregulated the expression of ID4. Reduced ID4 levels led to a negative feedback regulation of TGFBR1, enhancing the inhibitory effect of miR-210-3p on angiogenesis. In OA mice, miR-210-3p overexpression in ECs via adeno-associated virus (AAV) alleviated cartilage degradation, suppressed the type 17 immune response and relieved symptoms by attenuating subchondral Emcn+ vasculature and subchondral bone remodeling. In conclusion, we identified a miR-210-3p/TGFBR1/ID4 axis in subchondral ECs that modulates OA progression via subchondral angiogenesis, representing a potential OA therapy target.


Assuntos
Proteínas Inibidoras de Diferenciação , MicroRNAs , Osteoartrite , Receptor do Fator de Crescimento Transformador beta Tipo I , Animais , Camundongos , DNA , Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Osteoartrite/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , RNA Mensageiro/uso terapêutico , Sialomucinas , Proteínas Inibidoras de Diferenciação/metabolismo
14.
Front Public Health ; 10: 808873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35570909

RESUMO

Background: The outbreak of coronavirus disease 2019 (COVID-19) has endangered human health and life. This pandemic has changed people's lifestyle and affected the regular delivery of standard cancer treatment. In the present study, we aimed to explore the influencing factors of delayed treatment in patients with breast cancer during COVID-19 pandemic. Methods: This study was a cross-sectional investigation, and the subjects were patients who were discharged from the department of burn and plastic surgery after February 2020. All participants completed this study's online questionnaire based on the WeChat and Wenjuanxing platforms. Levels of anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS). Patients were divided into a delay group and non-delay group according to the occurrence of delayed treatment. Univariate analysis was performed by using the t test or chi-square test. A logistic regression model was employed to determine factors associated with delayed treatment. Results: The present study included a total of 397 patients with breast cancer, among whom delayed treatment occurred in 76 patients, accounting for 19.1%. Scores on both the anxiety subscale and depression subscale in delay group were significantly higher than those in non-delay group. Compared with non-delay group, we found that patients in delay group usually had a higher level of education (P = 0.020), worse self-feeling (P = 0.030), poor compliance of medical order (P = 0.042), and a higher prevalence of anxiety (P = 0.004) and depression (P = 0.012). Traffic inconvenience was also an important relevant factor for delayed treatment (P = 0.001). The prevalence of recurrence in delay group was higher than that in non-delay group (P = 0.018). By using logistic multivariate regression analysis, the results revealed that level of education and traffic inconvenience were independent factors influencing delayed treatment in patients with breast cancer during COVID-19 pandemic. Conclusion: The prevalence of delayed treatment in patients with breast cancer during COVID-19 pandemic is relatively high. Our findings reveal several influencing factors closely associated with delayed treatment, which is useful information that will be beneficial for patients to receive standardized therapy by taking targeted measures.


Assuntos
Neoplasias da Mama , COVID-19 , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Pandemias , SARS-CoV-2 , Tempo para o Tratamento
15.
Eur J Surg Oncol ; 48(6): 1272-1279, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35414404

RESUMO

BACKGROUND: Preoperative status of central lymph nodes is a key determinant of the initial surgical extent for papillary thyroid carcinoma (PTC). We aimed to develop and validate a nomogram based on preoperative clinical characteristics and ultrasound features to predict central lymph node status in patients with clinically lymph node-negative (cN0) T1/T2 PTC. METHODS: This retrospective study included 729 patients with cN0T1/T2 PTC who were treated between January 2015 and March 2020. Based on the ratio of 6:4, 431 patients who underwent surgeries relatively earlier comprised the training set to develop the nomogram, while the other 298 who underwent surgeries relatively later comprised validation set to validate the performance of nomogram. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to identify predictors of central lymph node metastasis (CLNM). These variables were used to construct a nomogram for predicting the risk of CLNM. The predictive performance, discriminative ability, calibration, and clinical utility of the nomogram model were evaluated in both sets. RESULTS: A total of 313 (42.9%) PTC patients were identified with CLNM. On multivariate logistic regression analyses, malegender, younger age, larger maximum diameter, multifocality, capsular invasion, infiltrative margins, intra-nodular vascularity, and aspect ratio >1 were independent risk factors for CLNM. Nomogram integrating these 8 factors showed excellent discrimination in the training [area under the curve (AUC): 0.788] and validation (AUC: 0.829) sets, and obtained well-fitted calibration curves. The cut-off value of this nomogram was 0.410 (∼245 points). Decision curve analysis confirmed the clinical utility of the nomogram. CONCLUSION: The CLNM-predicting nomogram can facilitate stratification of cN0T1/T2 PTC patients. Prophylactic central neck lymph node dissection can be considered for those with high nomogram scores.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Papilar/patologia , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Nomogramas , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
16.
Bioengineered ; 13(4): 9233-9247, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35378052

RESUMO

Osteoarthritis (OA) is the most prevalent type of degenerative joint disease, and its pathological progression is highly associated with oxidative stress. Natural antioxidants can attenuate oxidative stress and chondrocyte injury, suggesting that antioxidants have potential applications in the management of OA. Ellagic acid (EA), a natural polyphenol derived from fruits or nuts, exerts antioxidant and anti-inflammatory effects in diseases related to oxidative stress. Herein, we investigated the effects of EA on interleukin-1ß (IL-1ß)-induced oxidative stress and degeneration in C28/I2 human chondrocytes. EA efficiently suppressed IL-1ß-induced oxidative stress and ameliorated oxidative stress-induced dysfunction of chondrocytes, as indicated by the promotion of cartilage matrix secretion. Moreover, EA remarkably suppressed cell apoptosis and senescence, and reduced the expression of proinflammatory factors and metalloproteinases, suggesting that EA could alleviate chondrocyte injury under oxidative stress. Mechanistically, EA upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) as well as its downstream targets NADPH quinone oxidoreductase 1 and heme oxygenase-1. ML385, a specific Keap1/Nrf2 pathway inhibitor, blocked the antioxidant and chondroprotective effects of EA. Our findings demonstrated that EA could attenuate oxidative stress and exert protective effects on chondrocytes by upregulating the Keap1/Nrf2 signaling pathway.


Assuntos
Condrócitos , Fator 2 Relacionado a NF-E2 , Antioxidantes/farmacologia , Condrócitos/metabolismo , Ácido Elágico/metabolismo , Ácido Elágico/farmacologia , Humanos , Interleucina-1beta/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo
17.
Cell Transplant ; 30: 9636897211053870, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34699265

RESUMO

Osteonecrosis of the femoral head (ONFH) is a leading cause of mobility impairment which may lead to a total hip replacement. Recent studies have found tendon derived stem cells (TDSCs) might be an ideal cell source for musculoskeletal tissue regeneration. And our previous study has shown Sox11 could promote osteogenesis of bone marrow-derived MSCs. However, the effect of TDSCs or Sox11 over-expressing TDSCs (TDSCs-Sox11) on bone regeneration in ONFH has not been investigated. In the present study, TDSCs were infected with AAV carrying Sox11 or empty vector. We showed that Sox11 could promote the proliferation and osteogenic differentiation of TDSCs, as well as angiogenesis in vitro. The western blot analysis showed that Sox11 could activate the PI3K/Akt signaling pathway to promote osteogenesis of TDSCs. Finally, using a rabbit model of hormone-induced ONFH, our result demonstrated that local administration of TDSCs or TDSCs overexpressing Sox11 could accelerate bone regeneration in necrotic femoral heads, and TDSCs overexpressing Sox11 showed better effects. TDSCs over-expressing Sox11 might be a promising cell source for stem cell therapy to promote bone regeneration, such as ONFH, fracture, bone defect, and so on.


Assuntos
Cabeça do Fêmur/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética , Fatores de Transcrição SOXC/metabolismo , Animais , Diferenciação Celular , Humanos , Coelhos
18.
Medicine (Baltimore) ; 100(38): e27171, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559105

RESUMO

ABSTRACT: This study was designed to select ideal lead compounds and preclinical drug candidates http://dict.youdao.com/w/eng/preclinical_drug_candidate/javascript:void (0); with inhibitory effect on c-MET from the drug library (ZINC database).A battery of computer-aided virtual techniques was used to identify possible inhibitors of c-MET. A total of 17,931 ligands were screened from the ZINC15 database. LibDock is applied for structure-based screening followed by absorption, distribution, metabolic, and excretion, and toxicity prediction. Molecular docking was conducted to confirm the binding affinity mechanism between the ligand and c-MET. Molecular dynamics simulations were used to assess the stability of ligand-c-MET complexes.Two new natural compounds ZINC000005879645 and ZINC000002528509 were found to bind to c-MET in the ZINC database, showing higher binding affinity. In addition, they were predicted to have lower rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential, and high tolerance to cytochrome P4502D6. Molecular dynamics simulation shows that ZINC000005879645 and ZINC000002528509 have more favorable potential energies with c-MET, which could exist stably in the natural environment.This study suggests that ZINC000005879645 and ZINC000002528509 are ideal latent inhibitors of c-MET targeting. As drug candidates, these 2 compounds have low cytotoxicity and hepatotoxicity as well as important implications for the design and improvement of c-MET target drugs.


Assuntos
Ligantes , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Bases de Dados Factuais , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Simulação de Dinâmica Molecular
19.
Orthop Surg ; 13(5): 1563-1569, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34109746

RESUMO

OBJECTIVE: To introduce posteromedial corner release with the knee in the figure-of-four position versus the conventional position for varus knee arthroplasty. METHODS: This is a retrospective study. From March 2015 to September 2019, a series of 123 patients (139 knees) with varus knee were randomly and blindly allocated to experimental group (60 patients; 68 knees) and control group (57 patients; 65 knees). Patients in experimental group underwent posteromedial corner release with the knee in the figure-of-four position; and patients in control group with the knee in the conventional position. If soft tissue balance was not completely achieved or the medial gap was still tight, an additional loosening technique were used to achieve symmetric medial and lateral space in both groups. Time for soft tissue balancing was defined as the time from the start of the spacer test to the end of the balance test. Length of release was defined as the distance from the osteotomy surface of the tibial plateau to the farthest structures released. The rating system of Hospital for Special Surgery (HSS) knee score was used to evaluate the clinical results. Quantitative variables were described as mean and standard deviation, and compared by one-way analysis of variance. RESULTS: The mean age of experimental group and control group was 70.2 ± 8.7 years and 68.7 ± 6.2 years, respectively (P > 0.05). Preoperatively, the mean HSS score of the groups was 38.2 ± 11.3 and 39.1 ± 10.7, respectively (P > 0.05). The mean varus knee angle was 19.7° ± 9.3° and 19.3° ± 10.7°, respectively (P > 0.05). The mean time for soft tissue balancing was 8.4 ± 3.3 min and 11.3 ± 6.9 min in experimental and control group, respectively (P < 0.05). The mean length of releasing posteromedial corner structures was 35.5 ± 13.4 mm and 27.3 ± 9.7 mm in experimental and control group, respectively (P < 0.05). Additional special loosening techniques were performed in eight knees in experimental group and seven knees in control group. The HSS scores 5 years after surgery were 95.1 ± 16.9 and 94.8 ± 17.2 respectively (P > 0.05). No complications were found during the follow-up time, and the clinical symptoms were observed to be significantly improved in the patients. CONCLUSION: The posteromedial corner can be released more extensively and thoroughly when the knee is placed in the figure-of-four position during varus knee arthroplasty.


Assuntos
Artroplastia do Joelho/métodos , Posicionamento do Paciente , Idoso , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
20.
J Orthop Surg Res ; 16(1): 353, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059087

RESUMO

BACKGROUND: Placement of femoral stem in excessive anteversion or retroversion can cause reduced range of motion, prosthetic impingement, and dislocation. The aim of this study was to assess the operative femoral anteversion in patients treated with total hip arthroplasty (THA) and analyze the need of adjusting stem anteversion. METHODS: We retrospectively included 101 patients (126 hips) who underwent cementless THA with a manual goniometer to determine the femoral anteversion between October 2017 and December 2018. The operative femoral anteversion we measured was recorded during THA. We further divided those hips into three subgroups based on the range of operative femoral anteversion: group 1 (<10°), group 2 (10-30°), and group 3 (>30°) and compared the differences of their demographic data. Univariate and multivariate logistic regression were used to identify the influencing factors for the need of neck-adjustable femoral stem. The clinical and radiographic outcomes were also assessed. Perioperative complications were recorded. RESULTS: After THA, the Harris hip scores improved from 52.87 ± 15.30 preoperatively to 90.04 ± 3.31 at the last follow-up (p < 0.001). No implant loosening, stem subsidence, and radiolucent lines were observed on radiographs. No severe complications occurred and no components needed revision at the latest follow-up. The mean operative femoral anteversion was 14.21° ± 11.80° (range, -9 to 60°). Patients with femoral anteversion more than 30° were about 10 years younger than others. Femoral anteversion >30° was more common in patients with developmental dysplasia of the hip (DDH). There were totally 14 hips treated with the neck-adjustable femoral stem. From the univariate analysis, we can observe that female sex, diagnosis of DDH (compared with osteonecrosis), and higher operative femoral anteversion and its value >30° (compared with <10°) are associated with higher rates of using the neck-adjustable femoral stem. However, all these factors were no longer considered as independent influencing factors when mixed with other factors. CONCLUSIONS: This study highlighted the significance of operative femoral anteversion. Identification of abnormal femoral anteversion could assist in adjusting stem anteversion and reduce the risk of dislocation after THA.


Assuntos
Artroplastia de Quadril/métodos , Fêmur/patologia , Fêmur/cirurgia , Desenho de Prótese , Ajuste de Prótese , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Cimentos Ósseos , Feminino , Fêmur/diagnóstico por imagem , Fêmur/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Radiografia , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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