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1.
BMC Med Imaging ; 24(1): 259, 2024 Sep 28.
Article de Anglais | MEDLINE | ID: mdl-39342222

RÉSUMÉ

BACKGROUND: Magnetic Resonance Imaging (MRI) is extensively utilized in clinical diagnostics and medical research, yet the imaging process is often compromised by noise interference. This noise arises from various sources, leading to a reduction in image quality and subsequently hindering the accurate interpretation of image details by clinicians. Traditional denoising methods typically assume that noise follows a Gaussian distribution, thereby neglecting the more complex noise types present in MRI images, such as Rician noise. As a result, denoising remains a challenging and practical task. METHOD: The main research work of this paper focuses on modifying mask information based on a global mask mapper. The mask mapper samples all blind spot pixels on the denoised image and maps them to the same channel. By incorporating perceptual loss, it utilizes all available information to improve performance while avoiding identity mapping. During the denoising process, the model may mistakenly remove some useful information as noise, resulting in a loss of detail in the denoised image. To address this issue, we train a generative adversarial network (GAN) with adaptive hybrid attention to restore the detailed information in the denoised MRI images. RESULT: The two-stage model NRAE shows an improvement of nearly 1.4 dB in PSNR and approximately 0.1 in SSIM on clinical datasets compared to other classic models. Specifically, compared to the baseline model, PSNR is increased by about 0.6 dB, and SSIM is only 0.015 lower. From a visual perspective, NRAE more effectively restores the details in the images, resulting in richer and clearer representation of image details. CONCLUSION: We have developed a deep learning-based two-stage model to address noise issues in medical MRI images. This method not only successfully reduces noise signals but also effectively restores anatomical details. The current results indicate that this is a promising approach. In future work, we plan to replace the current denoising network with more advanced models to further enhance performance.


Sujet(s)
Imagerie par résonance magnétique , Rapport signal-bruit , Imagerie par résonance magnétique/méthodes , Humains , Traitement d'image par ordinateur/méthodes , Algorithmes , Apprentissage profond , Encéphale/imagerie diagnostique
2.
Nat Commun ; 15(1): 5899, 2024 Jul 13.
Article de Anglais | MEDLINE | ID: mdl-39003324

RÉSUMÉ

Challenges in direct catalytic oxidation of biomass-derived aldehyde and alcohol into acid with high activity and selectivity hinder the widespread biomass application. Herein, we demonstrate that a Pd/Ni(OH)2 catalyst with abundant Ni2+-O-Pd interfaces allows electrooxidation of 5-hydroxymethylfurfural to 2, 5-furandicarboxylic acid with a selectivity near 100 % and 2, 5-furandicarboxylic acid yield of 97.3% at 0.6 volts (versus a reversible hydrogen electrode) in 1 M KOH electrolyte under ambient conditions. The rate-determining step of the intermediate oxidation of 5-hydroxymethyl-2-furancarboxylic acid is promoted by the increased OH species and low C-H activation energy barrier at Ni2+-O-Pd interfaces. Further, the Ni2+-O-Pd interfaces prevent the agglomeration of Pd nanoparticles during the reaction, greatly improving the stability of the catalyst. In this work, Pd/Ni(OH)2 catalyst can achieve 100% 5-hydroxymethylfurfural conversion and >90% 2, 5-furandicarboxylic acid selectivity in a flow-cell and work stably over 200 h under a fixed cell voltage of 0.85 V.

3.
J Nanobiotechnology ; 22(1): 368, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38918787

RÉSUMÉ

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.


Sujet(s)
Ciments osseux , Peptide relié au gène de la calcitonine , Phosphates de calcium , Ostéogenèse , Porc miniature , Animaux , Phosphates de calcium/composition chimique , Phosphates de calcium/pharmacologie , Ciments osseux/pharmacologie , Ciments osseux/composition chimique , Souris , Suidae , Peptide relié au gène de la calcitonine/métabolisme , Ostéogenèse/effets des médicaments et des substances chimiques , Régénération osseuse/effets des médicaments et des substances chimiques , Rachis/chirurgie , Ganglions sensitifs des nerfs spinaux/métabolisme , Ganglions sensitifs des nerfs spinaux/effets des médicaments et des substances chimiques , Lignée cellulaire , Magnésium/pharmacologie , Magnésium/composition chimique
4.
ACS Biomater Sci Eng ; 10(5): 3203-3217, 2024 05 13.
Article de Anglais | MEDLINE | ID: mdl-38557027

RÉSUMÉ

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.


Sujet(s)
Encéphale , Hydrogels , Cellules souches pluripotentes induites , Organoïdes , Moelle spinale , Organoïdes/effets des médicaments et des substances chimiques , Organoïdes/cytologie , Organoïdes/métabolisme , Humains , Animaux , Moelle spinale/cytologie , Cellules souches pluripotentes induites/cytologie , Cellules souches pluripotentes induites/effets des médicaments et des substances chimiques , Hydrogels/composition chimique , Hydrogels/pharmacologie , Encéphale/métabolisme , Rats , Matrice extracellulaire décellularisée/composition chimique , Matrice extracellulaire décellularisée/pharmacologie , Matrice extracellulaire/métabolisme , Matrice extracellulaire/composition chimique , Laminine/pharmacologie , Laminine/composition chimique , Protéoglycanes/composition chimique , Rat Sprague-Dawley , Association médicamenteuse , Collagène
5.
ACS Biomater Sci Eng ; 10(5): 3218-3231, 2024 05 13.
Article de Anglais | MEDLINE | ID: mdl-38593429

RÉSUMÉ

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.


Sujet(s)
Différenciation cellulaire , Matrice extracellulaire décellularisée , Hydrogels , Cellules souches pluripotentes induites , Organoïdes , Placenta , Moelle spinale , Humains , Organoïdes/cytologie , Organoïdes/métabolisme , Organoïdes/effets des médicaments et des substances chimiques , Femelle , Placenta/cytologie , Cellules souches pluripotentes induites/cytologie , Cellules souches pluripotentes induites/effets des médicaments et des substances chimiques , Cellules souches pluripotentes induites/métabolisme , Grossesse , Hydrogels/composition chimique , Hydrogels/pharmacologie , Moelle spinale/cytologie , Moelle spinale/métabolisme , Différenciation cellulaire/effets des médicaments et des substances chimiques , Matrice extracellulaire décellularisée/pharmacologie , Matrice extracellulaire décellularisée/composition chimique , Matrice extracellulaire/métabolisme , Matrice extracellulaire/composition chimique , Laminine/pharmacologie , Laminine/composition chimique
6.
Front Immunol ; 15: 1362970, 2024.
Article de Anglais | MEDLINE | ID: mdl-38629071

RÉSUMÉ

Background: T cell exhaustion in the tumor microenvironment has been demonstrated as a substantial contributor to tumor immunosuppression and progression. However, the correlation between T cell exhaustion and osteosarcoma (OS) remains unclear. Methods: In our present study, single-cell RNA-seq data for OS from the GEO database was analysed to identify CD8+ T cells and discern CD8+ T cell subsets objectively. Subgroup differentiation trajectory was then used to pinpoint genes altered in response to T cell exhaustion. Subsequently, six machine learning algorithms were applied to develop a prognostic model linked with T cell exhaustion. This model was subsequently validated in the TARGETs and Meta cohorts. Finally, we examined disparities in immune cell infiltration, immune checkpoints, immune-related pathways, and the efficacy of immunotherapy between high and low TEX score groups. Results: The findings unveiled differential exhaustion in CD8+ T cells within the OS microenvironment. Three genes related to T cell exhaustion (RAD23A, SAC3D1, PSIP1) were identified and employed to formulate a T cell exhaustion model. This model exhibited robust predictive capabilities for OS prognosis, with patients in the low TEX score group demonstrating a more favorable prognosis, increased immune cell infiltration, and heightened responsiveness to treatment compared to those in the high TEX score group. Conclusion: In summary, our research elucidates the role of T cell exhaustion in the immunotherapy and progression of OS, the prognostic model constructed based on T cell exhaustion-related genes holds promise as a potential method for prognostication in the management and treatment of OS patients.


Sujet(s)
Tumeurs osseuses , Ostéosarcome , Humains , Analyse de l'expression du gène de la cellule unique , Épuisement des cellules T , Ostéosarcome/génétique , Tumeurs osseuses/génétique , Immunité , Microenvironnement tumoral/génétique , Protéines de liaison à l'ADN , Enzymes de réparation de l'ADN
7.
J Orthop Surg Res ; 19(1): 209, 2024 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-38561837

RÉSUMÉ

BACKGROUND: Previous studies have demonstrated the clinical efficacy of decompression alone in lower-grade spondylolisthesis. A higher rate of surgical revision and a lower rate of back pain relief was also observed. However, there is a lack of relevant biomechanical evidence after decompression alone for lower-grade spondylolisthesis. PURPOSE: Evaluating the biomechanical characteristics of total laminectomy, hemilaminectomy, and facetectomy for lower-grade spondylolisthesis by analyzing the range of motion (ROM), intradiscal pressure (IDP), annulus fibrosus stress (AFS), facet joints contact force (FJCF), and isthmus stress (IS). METHODS: Firstly, we utilized finite element tools to develop a normal lumbar model and subsequently constructed a spondylolisthesis model based on the normal model. We then performed total laminectomy, hemilaminectomy, and one-third facetectomy in the normal model and spondylolisthesis model, respectively. Finally, we analyzed parameters, such as ROM, IDP, AFS, FJCF, and IS, for all the models under the same concentrate force and moment. RESULTS: The intact spondylolisthesis model showed a significant increase in the relative parameters, including ROM, AFS, FJCF, and IS, compared to the intact normal lumbar model. Hemilaminectomy and one-third facetectomy in both spondylolisthesis and normal lumbar models did not result in an obvious change in ROM, IDP, AFS, FJCF, and IS compared to the pre-operative state. Moreover, there was no significant difference in the degree of parameter changes between the spondylolisthesis and normal lumbar models after undergoing the same surgical procedures. However, total laminectomy significantly increased ROM, AFS, and IS and decreased the FJCF in both normal lumbar models and spondylolisthesis models. CONCLUSION: Hemilaminectomy and one-third facetectomy did not have a significant impact on the segment stability of lower-grade spondylolisthesis; however, patients with LDS undergoing hemilaminectomy and one-third facetectomy may experience higher isthmus stress on the surgical side during rotation. In addition, total laminectomy changes the biomechanics in both normal lumbar models and spondylolisthesis models.


Sujet(s)
Arthrodèse vertébrale , Spondylolisthésis , Humains , Spondylolisthésis/chirurgie , Analyse des éléments finis , Vertèbres lombales/chirurgie , Laminectomie/méthodes , Arthrodèse vertébrale/méthodes , Phénomènes biomécaniques , Amplitude articulaire/physiologie , Décompression
8.
BMC Pediatr ; 24(1): 236, 2024 Apr 03.
Article de Anglais | MEDLINE | ID: mdl-38570804

RÉSUMÉ

PURPOSE: This study aims to analyze the clinical characteristics of Chinese children with spinal cord injury (SCI) without radiographic abnormality (SCIWORA) and explore their contributing factors and mechanisms of occurrence. METHODS: A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with SCIWORA from January 2005 to May 2020. Epidemiological, etiological, mechanistic, therapeutic, and outcome aspects were analyzed. RESULTS: A total of 47 patients with SCIWORA were included in this study, comprising 16 males and 31 females. The age range was 4 to 12 years, with an average age of 7.49 ± 2.04 years, and 70% of the patients were below eight. Sports-related injuries constituted 66%, with 70% attributed to dance backbend practice. Thoracic segment injuries accounted for 77%. In the American Spinal Injury Association (ASIA) classification, the combined proportion of A and B grades accounted for 88%. Conservative treatment was chosen by 98% of the patients, with muscle atrophy, spinal scoliosis, hip joint abnormalities, and urinary system infections being the most common complications. CONCLUSION: SCIWORA in Chinese children is more prevalent in those under eight years old, with a higher incidence in females than males. Thoracic spinal cord injuries are predominant, dance backbend as a primary contributing factor, and the social environment of "neijuan" is a critical potential inducing factor. Furthermore, the initial severity of the injury plays a decisive role in determining the prognosis of SCIWORA.


Sujet(s)
Traumatismes de la moelle épinière , Mâle , Femelle , Enfant , Humains , Enfant d'âge préscolaire , Études rétrospectives , Traumatismes de la moelle épinière/imagerie diagnostique , Traumatismes de la moelle épinière/épidémiologie , Traumatismes de la moelle épinière/étiologie , Radiographie , Pronostic , Chine/épidémiologie , Imagerie par résonance magnétique
9.
Bioact Mater ; 37: 51-71, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38515609

RÉSUMÉ

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1ß)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.

10.
Int J Surg ; 110(6): 3178-3189, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38498354

RÉSUMÉ

OBJECTIVE: To evaluate the long-term clinical efficacy of three different surgical approaches in treating thoracolumbar tuberculosis. METHODS: A total of 176 patients with thoracolumbar tuberculosis, treated with open surgery at two hospitals, were retrospectively analyzed. Patients were stratified into three groups based on the surgical approach: anterior-only (AO), posterior-only (PO), and anterior-posterior combined (AP) approaches. Collected data encompassed operative duration, intraoperative blood loss, hospital stay length, complications, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI), American Spinal Injury Association (ASIA) classification, and radiographic measurements of segmental lordotic Cobb angles, correction angles, and correction rates. RESULTS: The minimum duration of follow-up among all patients was 10 years. Postoperatively, all patients experienced a reduction in ESR and CRP, with normalization occurring within 3 months and sustained normal at the last follow-up. The AP group had a longer operative duration and higher intraoperative blood loss than the other two groups. The Cobb correction rates for AO, PO, and AP were (56.33±6.62)%, (72.82±5.66)%, and (74.45±5.78)%, respectively. The correction loss of Cobb angles for AO, PO, and AP were (2.85±1.01)°, (1.42±0.97)°, and (1.19±0.89)°, respectively. Patients in all groups showed significant improvement in VAS scores and ODI postoperatively, with no notable intergroup differences. The neurological recovery rates for the AO, PO, and AP groups were 84.62, 87.10, and 83.72%, respectively, while the complication rates were 12.73, 16.98, and 22.06%, respectively. CONCLUSION: An anterior-only approach is recommended for cases with localized lesions and smaller angular deformities. For patients with multisegmental lesions and larger angular deformities, a posterior-only or anterior-posterior combined approach is advised, with a preference for the posterior-only approach.


Sujet(s)
Vertèbres lombales , Vertèbres thoraciques , Tuberculose vertébrale , Humains , Études rétrospectives , Mâle , Femelle , Adulte , Tuberculose vertébrale/chirurgie , Vertèbres thoraciques/chirurgie , Adulte d'âge moyen , Vertèbres lombales/chirurgie , Études de suivi , Études cas-témoins , Résultat thérapeutique , Jeune adulte
11.
Sci Rep ; 14(1): 3505, 2024 Feb 12.
Article de Anglais | MEDLINE | ID: mdl-38347073

RÉSUMÉ

Hail, a highly destructive weather phenomenon, necessitates critical identification and forecasting for the protection of human lives and properties. The identification and forecasting of hail are vital for ensuring human safety and safeguarding assets. This research proposes a deep learning algorithm named Dual Attention Module EfficientNet (DAM-EfficientNet), based on EfficientNet, for detecting hail weather conditions. DAM-EfficientNet was evaluated using FY-4A satellite imagery and real hail fall records, achieving an accuracy of 98.53% in hail detection, a 97.92% probability of detection, a false alarm rate of 2.08%, and a critical success index of 95.92%. DAM-EfficientNet outperforms existing deep learning models in terms of accuracy and detection capability, with fewer parameters and computational needs. The results validate DAM-EfficientNet's effectiveness and superior performance in hail weather detection. Case studies indicate that the model can accurately forecast potential hail-affected areas and times. Overall, the DAM-EfficientNet model proves to be effective in identifying hail weather, offering robust support for weather disaster alerts and prevention. It holds promise for further enhancements and broader application across more data sources and meteorological parameters, thereby increasing the precision and timeliness of hail forecasting to combat hail disasters and boost public safety.

12.
Front Immunol ; 14: 1188256, 2023.
Article de Anglais | MEDLINE | ID: mdl-37457709

RÉSUMÉ

Background: IBSP is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family that plays a vital role in bone formation, renewal and repair. Emerging evidence revealed that IBSP participated in the tumorigenesis and progression in some cancers. However, its significance in tumour prognosis and immunotherapy is still unknown. Methods: In the current study, we studied the role of IBSP in tumorigenesis, tumor diagnosis, genomic heterogeneity, methylation modifications, immune infiltration, and therapy response in pan-cancer. In addition, we constructed a risk score model to assessed the prognostic classification efficiency of IBSP using the co-expression genes of IBSP in osteosarcoma (OS), and analyzed the expression and role of IBSP in OS through a series of assays in vitro. Results: IBSP was upregulated in various cancers compared to the paired normal tissues, and it was strongly correlated with the prognosis, pathological stage, diagnostic accuracy, genomic heterogeneity, methylation modification, immune infiltration, immune and checkpoint. Moreover, the predictive model we established in combination with the clinical characteristics of OS patients showed high survival predictive power in these individuals. The assays in vitro showed that IBSP promoted the proliferation, migration and invasion of OS cells, which further confirmed IBSP's role in cancers. Conclusions: Our research revealed the multifunctionality of IBSP in the tumorigenesis, progression and therapy in various cancers, which demonstrated that IBSP may serve as a potential prognostic biomarker and a novel immunotherapy target in pan-cancer.


Sujet(s)
Tumeurs osseuses , Ostéosarcome , Humains , Pronostic , Ostéosarcome/génétique , Ostéosarcome/thérapie , Marqueurs biologiques , Carcinogenèse , Transformation cellulaire néoplasique , Immunothérapie , Tumeurs osseuses/génétique , Tumeurs osseuses/thérapie
13.
ACS Appl Mater Interfaces ; 15(23): 28036-28043, 2023 Jun 14.
Article de Anglais | MEDLINE | ID: mdl-37253144

RÉSUMÉ

The development of single-atom catalysts with effective interfaces for biomass conversion is a promising but challenging research area. In this study, a Ru1/CoOx catalyst was successfully fabricated with the impregnation method, which featured Ru single atoms on a cobalt oxide substrate. The Ru1/CoOx catalyst showed superior performance in the selective electrooxidation of 5-hydroxymethylfurfural (HMF) to produce 2,5-furandicarboxylic acid (FDCA), a high value-added product. The introduction of Ru single atoms with an ultralow loading of ∼0.5 wt % was revealed to accelerate the electroredox of Co2+/Co3+/Co4+ and improve the intrinsic activity of the CoOx substrate with an FDCA selectivity of 76.5%, which is better than that of the pristine CoOx electrocatalysts (62.7%). The interfacial synergistic effect of the Ru1/CoOx interface clarified that Ru single atoms can enhance the adsorption of HMF at the Ru1/CoOx interface, which promoted the rate-determining step of the selective C-H bond activation for FDCA production. This finding provides valuable insights into the rational design of single-atom catalysts with functional interfaces for biomass upgrading.

14.
ACS Nano ; 17(4): 3818-3837, 2023 02 28.
Article de Anglais | MEDLINE | ID: mdl-36787636

RÉSUMÉ

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 µm, and also had the ability to activate the PDGFRß of NSCs more effectively than PDGF-MPH. In vitro, PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo, PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.


Sujet(s)
Hydrogels , Traumatismes de la moelle épinière , Rats , Animaux , Hydrogels/pharmacologie , Hydrogels/usage thérapeutique , Facteur de croissance dérivé des plaquettes/pharmacologie , Facteur de croissance dérivé des plaquettes/usage thérapeutique , Différenciation cellulaire , Microsphères , Études prospectives , Traumatismes de la moelle épinière/traitement médicamenteux , Traumatismes de la moelle épinière/anatomopathologie , Peptides/pharmacologie , Moelle spinale/anatomopathologie
15.
Aging (Albany NY) ; 13(17): 21142-21154, 2021 09 07.
Article de Anglais | MEDLINE | ID: mdl-34493692

RÉSUMÉ

BACKGROUND: Osteosarcoma (OS) is a common disease in the world, and its pathogenesis is still unclear. This study aims to identify the key genes that promote the proliferation, invasion, and metastasis of osteosarcoma cells. METHOD: GSE124768 and GSE126209 were downloaded from the Gene Expression Omnibus (GEO) database. The gene ontology and enrichment pathway were analyzed by FunRich software. qPCR and Western blot were used to detect the gene expression. After gene knockdown, Transwell and wound healing assays were conducted on osteosarcoma cells to detect whether the genes were defined before enhancing the invasion of osteosarcoma. RESULTS: Totally, 341 mRNAs were found to be regulated differentially in osteosarcoma cells compared to osteoblasts. In addition, the expression level of Serglycin (SRGN) in osteosarcoma cells was higher than that in human osteoblasts. The invasion and proliferation ability of osteosarcoma cells with upregulated Serglycin was significantly increased, and on the contrary, decreased after Serglycin knockdown. Moreover, we preliminarily found that Serglycin may associate with the JAK/STAT signaling pathway. CONCLUSIONS: By using microarray and bioinformatics analyses, differently expressed mRNAs were identified and a complete gene network was constructed. To our knowledge, we describe for the first time Serglycin as a potential biomarker.


Sujet(s)
Tumeurs osseuses/métabolisme , Réseaux de régulation génique , Gènes tumoraux , Janus kinases/métabolisme , Ostéosarcome/métabolisme , Protéoglycanes/métabolisme , Facteurs de transcription STAT/métabolisme , Protéines du transport vésiculaire/métabolisme , Tumeurs osseuses/génétique , Os et tissu osseux/métabolisme , Os et tissu osseux/anatomopathologie , Lignée cellulaire tumorale , Mouvement cellulaire , Prolifération cellulaire , Expression des gènes , Régulation de l'expression des gènes tumoraux , Humains , Kinase Janus-2/métabolisme , Invasion tumorale , Ostéoblastes/métabolisme , Ostéosarcome/génétique , ARN messager/métabolisme , Facteur de transcription STAT-3 , Transduction du signal , Régulation positive
16.
Oncogene ; 40(24): 4137-4150, 2021 06.
Article de Anglais | MEDLINE | ID: mdl-34017080

RÉSUMÉ

BRAF inhibitors (BRAFi) that target BRAF V600E kinase, a driver mutation found in 50% of melanomas, show a significant antitumor response, but the common emergence of acquired resistance remains a challenge. Abnormal expression of RAF isoforms CRAF and ARAF reactivates pERK1/2, which plays crucial roles in the acquisition of resistance of melanoma cells. However, the mechanisms of dysregulation of RAF isoforms in resistant melanoma cells remain unknown. Here, we identified NONO interacted with and stabilized both CRAF and ARAF in melanoma cells, and that NONO was acetylated at 198K by p300 acetyltransferase, which stabilized NONO via antagonizing its ubiquitination/degradation mediated by RNF8. The upregulation of both p300 and NONO promoted the rebound of pERK1/2 and the subsequent resistance of melanoma cells to BRAFi, and the activation of ERK1/2 in turn induced p300 to form a positive feedback loop in resistant melanoma cells. There was a positive correlation between p300 and NONO in resistant melanoma cells and clinical samples, and p300 inhibitor C646 overcame the resistance of resistant melanoma cells to BRAF inhibitors in vitro and in vivo. Our findings reveal that targeting the positive feedback loop of p300-NONO-CRAF/ARAF-pERK1/2 may be excellent strategies to overcome the resistance of BRAF inhibitors for melanoma patients.


Sujet(s)
Protéines de liaison à l'ADN/génétique , Protéine p300-E1A/génétique , Mélanome/traitement médicamenteux , Mélanome/génétique , Inhibiteurs de protéines kinases/pharmacologie , Protéines proto-oncogènes B-raf/génétique , Protéines de liaison à l'ARN/génétique , Lignée cellulaire tumorale , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Résistance aux médicaments antinéoplasiques/génétique , Cellules HEK293 , Humains , Isoformes de protéines/génétique , Régulation positive/effets des médicaments et des substances chimiques , Régulation positive/génétique
17.
Biosci Rep ; 41(4)2021 04 30.
Article de Anglais | MEDLINE | ID: mdl-33860796

RÉSUMÉ

BACKGROUND: WT161, as a selective HDAC6 inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of the present study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms. METHODS: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo. RESULTS: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of protein kinase-B (AKT). More importantly, WT161 showed synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo. CONCLUSIONS: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.


Sujet(s)
Antinéoplasiques/usage thérapeutique , Fluorouracil/usage thérapeutique , Inhibiteurs de désacétylase d'histone/usage thérapeutique , Acides hydroxamiques/usage thérapeutique , Ostéosarcome/traitement médicamenteux , Dérivés du terphényle/usage thérapeutique , Animaux , Antinéoplasiques/pharmacologie , Apoptose , Lignée cellulaire tumorale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Synergie des médicaments , Femelle , Fluorouracil/pharmacologie , Histone deacetylase 6/antagonistes et inhibiteurs , Inhibiteurs de désacétylase d'histone/pharmacologie , Humains , Acides hydroxamiques/pharmacologie , Souris , Souris nude , Ostéosarcome/métabolisme , Phosphohydrolase PTEN/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Dérivés du terphényle/pharmacologie
18.
Cancer Cell Int ; 21(1): 209, 2021 Apr 13.
Article de Anglais | MEDLINE | ID: mdl-33849550

RÉSUMÉ

The metabolic change of tumor cells is an extremely complicated process that involves the intersection and integration of various signal pathways. Compared with normal tissues, cancer cells show distinguished metabolic characteristics called metabolic reprogramming, which has been considered as a sign of cancer occurrence. With the deepening of tumor research in recent years, people gradually found that amino acid metabolism played crucial roles in cancer progression. Long non-coding RNAs (lncRNAs), which are implicated in many important biological processes, were firstly discovered dysregulating in cancer tissues and participating in extensive regulation of tumorigenesis. This review focuses on the reprogramming of amino acid metabolism in cancers and how lncRNAs participate in the regulatory network by interacting with other macromolecular substances. Understanding the functions of lncRNA in amino acid reprogramming in tumors might provide a new vision on the mechanisms of tumorigenesis and the development of new approaches for cancer therapy.

19.
J Am Acad Dermatol ; 84(6): 1782-1791, 2021 Jun.
Article de Anglais | MEDLINE | ID: mdl-32828861

RÉSUMÉ

BACKGROUND: Patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have high mortality rates. Disseminated intravascular coagulation has been reported in SJS/TEN patients. The influence of this lethal complication in patients with SJS/TEN is not well known. OBJECTIVE: This study aimed to investigate the risk and outcomes of disseminated intravascular coagulation in patients with SJS/TEN. METHODS: We analyzed the disseminated intravascular coagulation profiles of patients receiving a diagnosis of SJS/TEN between 2010 and 2019. RESULTS: We analyzed 150 patients with SJS/TEN (75 with SJS, 22 with overlapping SJS/TEN, and 53 with TEN) and their complete disseminated intravascular coagulation profiles. Disseminated intravascular coagulation was diagnosed in 32 patients (21.3%), primarily those with TEN. It was significantly associated with systemic complications, including gastrointestinal bleeding, respiratory failure, renal failure, liver failure, infection, and bacteremia. Additionally, SJS/TEN patients with disseminated intravascular coagulation had elevated procalcitonin levels. Among patients with SJS/TEN, disseminated intravascular coagulation was associated with a greater than 10-fold increase in mortality (78.1% vs 7%). LIMITATIONS: The study limitations include small sample size and a single hospital system. CONCLUSION: Disseminated intravascular coagulation is a potential complication of SJS/TEN and associated with higher mortality. Early recognition and appropriate management of this critical complication are important for patients with SJS/TEN.


Sujet(s)
Coagulation intravasculaire disséminée/étiologie , Coagulation intravasculaire disséminée/mortalité , Hémorragie gastro-intestinale/complications , Syndrome de Stevens-Johnson/complications , Syndrome de Stevens-Johnson/mortalité , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Bactériémie/complications , Bactériémie/microbiologie , Femelle , Humains , Estimation de Kaplan-Meier , Défaillance hépatique/complications , Mâle , Adulte d'âge moyen , Insuffisance rénale/complications , Insuffisance respiratoire/complications , Taux de survie
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