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1.
Front Bioeng Biotechnol ; 12: 1460870, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280342

RESUMEN

Introduction: Nanofibrous spheres, with their injectable format and biomimetic three-dimensional topologies that emulate the complexity of natural extracellular environments, have become increasingly attractive for applications in biomedical and regenerative medicine. Our research contributes to this growing field by detailing the design and fabrication of a novel series of polylactic acid/nano-hydroxyapatite (PLA/nHA) hybrid nanofibrous spheres. Methods: These advanced structures were created by integrating electrospinning and electrospray techniques, which allowed for precise control over the nanofibrous spheres, especially in size. We have conducted a comprehensive investigation into the nanofibrous spheres' capacity to deliver stem cells efficiently and maintain their viability post-implantation, as well as their potential to induce osteogenic differentiation. Results and Discussion: The results show that these nanofibrous spheres are biocompatible and injectable, effectively supporting the attachment, growth, and differentiation of bone marrow-derived mesenchymal stem cells while aiding in their targeted transportation to bone defect areas to execute their regenerative functions. The findings of this study could significantly impact the future development of biocompatible materials for a range of therapeutic applications, including bone tissue engineering and regenerative therapy.

2.
J Rehabil Med ; 56: jrm18701, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291912

RESUMEN

OBJECTIVE: Rehabilitation and recovery duration following anterior cruciate ligament reconstructive surgery play a pivotal role in restoring optimal knee functionality in athletes. This study aimed to explore the impact of a 3-month functional training programme aligned with enhanced recovery after surgery on recuperation subsequent to anterior cruciate ligament reconstructive surgery. DESIGN: A quasi-experimental study. SUBJECTS: A cohort of 34 patients aged 14 to 24, who underwent anterior cruciate ligament reconstructive surgery and adhered to enhanced recovery after surgery protocols during the perioperative period, were allocated to an experimental group and a control group according to their eligibility, capacity, and willingness to engage in the functional training programme. METHODS: The participants in the experimental group underwent a 3-month regimen of functional training following anterior cruciate ligament reconstructive surgery, whereas the control group followed a conventional recovery approach. Evaluations were conducted both prior to and following the 3-month recovery interval, utilizing the Y-Balance Test, Functional Movement Screening, and Isokinetic Knee Test. RESULTS: Assessment outcomes of the Y-Balance Test, Isokinetic Knee Test, and Functional Movement Screening exhibited significant enhancement (p < 0.05) within the experimental group, as opposed to the control group. These findings underscore that those athletes who undertook the 3-month functional training regimen within the experimental group exhibited heightened dynamic balance capabilities, increased knee joint mobility, and enhanced stability compared with their counterparts in the control group. CONCLUSION: Consequently, this underscores the efficacy of the 3-month functional training protocol aligned with enhanced recovery after surgery, as a means to effectively facilitate recuperation subsequent to anterior cruciate ligament reconstructive surgery.


Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior , Articulación de la Rodilla , Humanos , Reconstrucción del Ligamento Cruzado Anterior/rehabilitación , Masculino , Femenino , Adulto Joven , Adolescente , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/fisiología , Recuperación de la Función/fisiología , Atletas , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/rehabilitación , Terapia por Ejercicio/métodos , Adulto , Rango del Movimiento Articular/fisiología
3.
Brain Res ; 1846: 149252, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39326722

RESUMEN

Temozolomide (TMZ) is the first-line chemotherapeutic agent for malignant glioma, but its resistance limited the benefits of the treated patients. In this study, the role and significance of trimethylation of histone H3 lysine 27 (H3K27me3) in TMZ resistance were investigated. Data from twenty advanced glioma patients were collected, and their pathological samples were analyzed for H3K27me3 levels. TMZ sensitivity was compared between glioma cells U87 and TMZ-resistant cells U87TR, with H3K27me3 levels determined in both cells. The effects of H3K27me3 demethylases inhibitor GSK-J4, combined with TMZ, were assessed on the proliferation and migration of U87TR cells. The results indicated that a high level of H3K27me3 predicts longer disease free survival (DFS) and overall survival (OS) in glioma patients receiving TMZ treatment. The H3K27me3 level was lower in U87TR cells compared to U87 cells. GSK-J4 increased the H3K27me3 level in U87TR cells and decreased their resistance to TMZ. In summary, this study identified a novel marker of TMZ resistance in glioma and provided a new strategy to address this challenge. These findings are significant for improving the clinical treatment of glioma in the future.

4.
Front Pharmacol ; 15: 1397761, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104391

RESUMEN

Oral leukoplakia (OLK) is the most common oral precancerous lesion, and 3%-17% of OLK patients progress to oral squamous cell carcinoma. OLK is susceptible to recurrence and has no effective treatment. However, conventional drugs have significant side effects and limitations. Therefore, it is important to identify drugs that target OLK. In this study, scavenger receptor A (SR-A) was found to be abnormally highly expressed in the oral mucosal epithelial cells of OLK patients, whereas molecular biology studies revealed that low molecular weight fucoidan (LMWF) promoted apoptosis of dysplastic oral keratinocytes (DOK) and inhibited the growth and migration of DOK, and the inhibitory effect of LMWF on OLK was achieved by regulating the SR-A/Wnt signaling axis and related genes. Based on the above results and the special situation of the oral environment, we constructed LMWF/poly(caprolactone-co-lactide) nanofiber membranes with different structures for the in-situ treatment of OLK using electrospinning technology. The results showed that the nanofiber membranes with a shell-core structure had the best physicochemical properties, biocompatibility, and therapeutic effect, which optimized the LMWF drug delivery and ensured the effective concentration of the drug at the target point, thus achieving precise treatment of local lesions in the oral cavity. This has potential application value in inhibiting the development of OLK.

5.
Nanoscale Adv ; 6(16): 4230-4236, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39114139

RESUMEN

Biomaterials are widely used in regenerative medicine to repair full-thickness skin defect wounds. The adipose-derived stromal vascular fraction (SVF) shows pro-regenerative properties, however, the ex vivo biological activity of SVF is suppressed due to the lack of an external scaffold. Tilapia skin, as a sustained and recyclable biomaterial with low immunogenicity, was applied in the preparation of a hydrogel. The mixture of tilapia skin-derived gelatin and methacrylic anhydride as a scaffold facilitated the paracrine function of SVF and exerted a synergistic effect with SVF to promote wound healing. In this study, 30% (w/v) SVF was added to methacrylate-functionalized tilapia skin gelatin and subsequently exposed to UV irradiation to form a three-dimensional nano-scaffolding composite hydrogel (FG-SVF-3). The effects of paracrine growth factors, neovascularization, and collagen production on wound healing were extensively discussed. FG-SVF-3 displayed a pronounced wound healing ability via in vivo wound models. The FG-SVF-3 hydrogel enhanced the biocompatibility and the expression of EGF, bFGF, and VEGF. FG-SVF-3, as a promising wound dressing, exhibited superior ability to accelerate wound healing, skin regeneration, and wound closure.

6.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39000226

RESUMEN

E3 ubiquitin ligases (UBLs), as enzymes capable of specifically recognizing target proteins in the process of protein ubiquitination, play crucial roles in regulating responses to abiotic stresses such as drought, salt, and temperature. Abscisic acid (ABA), a plant endogenous hormone, is essential to regulating plant growth, development, disease resistance, and defense against abiotic stresses, and acts through a complex ABA signaling pathway. Hormone signaling transduction relies on protein regulation, and E3 ubiquitin ligases play important parts in regulating the ABA pathway. Therefore, this paper reviews the ubiquitin-proteasome-mediated protein degradation pathway, ABA-related signaling pathways, and the regulation of ABA-signaling-pathway-related genes by E3 ubiquitin ligases, aiming to provide references for further exploration of the relevant research on how plant E3 ubiquitin ligases regulate the ABA pathway.


Asunto(s)
Ácido Abscísico , Transducción de Señal , Ubiquitina-Proteína Ligasas , Ubiquitina-Proteína Ligasas/metabolismo , Ácido Abscísico/metabolismo , Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico , Ubiquitinación , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Reguladores del Crecimiento de las Plantas/metabolismo
7.
Biomater Adv ; 163: 213967, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39068744

RESUMEN

The healing of skin wounds is a continuous and coordinated process, typically accompanied by microbial colonization and growth. This may result in wound infection and subsequent delay in wound healing. Therefore, it is of particular importance to inhibit the growth of microorganisms in the wound environment. In this study, magnesium hydroxide-doped polycaprolactone (PCL/MH) nanofibrous spheres were fabricated by electrospinning and electrospray techniques to investigate their effects on infected wound healing. The prepared PCL/MH nanofibrous spheres had good porous structure and biocompatibility, providing a favorable environment for the delivery and proliferation of adipose stem cells. The incorporation of MH significantly enhanced the antimicrobial properties of the spheres, in particular, the inhibition of the growth of S. aureus and E. coli. We showed that such PCL/MH nanofibrous spheres had good antimicrobial properties and effectively promoted the regeneration of infected wound tissues, which provided a new idea for the clinical treatment of infected wounds.


Asunto(s)
Escherichia coli , Hidróxido de Magnesio , Nanofibras , Poliésteres , Piel , Staphylococcus aureus , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Nanofibras/química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Poliésteres/química , Piel/efectos de los fármacos , Piel/microbiología , Piel/lesiones , Animales , Hidróxido de Magnesio/química , Hidróxido de Magnesio/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Humanos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Andamios del Tejido/química
8.
bioRxiv ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38854085

RESUMEN

Transdifferentiation (TD), a somatic cell reprogramming process that eliminates pluripotent intermediates, creates cells that are ideal for personalized anti-cancer therapy. Here, we provide the first evidence that extracellular vesicles (EVs) from TD-derived induced neural stem cells (Exo-iNSCs) are an efficacious treatment strategy for brain cancer. We found that genetically engineered iNSCs generated EVs loaded with the tumoricidal gene product TRAIL at nearly twice the rate as their parental fibroblasts, and the TRAIL produced by iNSCs were naturally loaded into the lumen of EVs and arrayed across their outer membrane (Exo-iNSC-TRAIL). Uptake studies in ex vivo organotypic brain slice cultures showed Exo-iNSC-TRAIL selectively accumulates within tumor foci, and co-culture assays showed that Exo-iNSC-TRAIL killed metastatic and primary brain cancer cells more effectively than free TRAIL. In an orthotopic mouse model of brain cancer, Exo-iNSC-TRAIL reduced breast-to-brain tumor xenografts around 3000-fold greater than treatment with free TRAIL, with all Exo-iNSC-TRAIL treated animals surviving through 90 days post-treatment. In additional in vivo testing against aggressive U87 and invasive GBM8 glioblastoma tumors, Exo-iNSC-TRAIL also induced a statistically significant increase in survival. These studies establish a new easily generated, stable, tumor-targeted EV to efficaciously treat multiple forms of brain cancer.

9.
J Control Release ; 372: 433-445, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38908756

RESUMEN

Transdifferentiation (TD), a somatic cell reprogramming process that eliminates pluripotent intermediates, creates cells that are ideal for personalized anti-cancer therapy. Here, we provide the first evidence that extracellular vesicles (EVs) from TD-derived induced neural stem cells (Exo-iNSCs) are an efficacious treatment strategy for brain cancer. We found that genetically engineered iNSCs generated EVs loaded with the tumoricidal gene product TRAIL at nearly twice the rate of their parental fibroblasts, and TRAIL produced by iNSCs was naturally loaded into the lumen of EVs and arrayed across their outer membrane (Exo-iNSC-TRAIL). Uptake studies in ex vivo organotypic brain slice cultures showed that Exo-iNSC-TRAIL selectively accumulates within tumor foci, and co-culture assays demonstrated that Exo-iNSC-TRAIL killed metastatic and primary brain cancer cells more effectively than free TRAIL. In an orthotopic mouse model of brain cancer, Exo-iNSC-TRAIL reduced breast-to-brain tumor xenografts by approximately 3000-fold compared to treatment with free TRAIL, with all Exo-iNSC-TRAIL treated animals surviving through 90 days post-treatment. In additional in vivo testing against aggressive U87 and invasive GBM8 glioblastoma tumors, Exo-iNSC-TRAIL also induced a statistically significant increase in survival. These studies establish a novel, easily generated, stable, tumor-targeted EV to efficaciously treat multiple forms of brain cancer.


Asunto(s)
Neoplasias Encefálicas , Exosomas , Células-Madre Neurales , Ligando Inductor de Apoptosis Relacionado con TNF , Animales , Ligando Inductor de Apoptosis Relacionado con TNF/administración & dosificación , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Exosomas/metabolismo , Humanos , Línea Celular Tumoral , Femenino , Ratones , Ratones Desnudos
10.
Mater Today Bio ; 26: 101099, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38840797

RESUMEN

Advancements in tissue engineering are crucial for successfully healing tendon-bone connections, especially in situations like anterior cruciate ligament (ACL) restoration. This study presents a new and innovative three-dimensional scaffold, reinforced with nanofibers, that is specifically intended for acellular tendon complexes. The scaffold consists of a distinct layered arrangement comprising an acellular tendon core, a middle layer of polyurethane/type I collagen (PU/Col I) yarn, and an outside layer of poly (L-lactic acid)/bioactive glass (PLLA/BG) nanofiber membrane. Every layer is designed to fulfill specific yet harmonious purposes. The acellular tendon core is a solid structural base and a favorable environment for tendon cell functions, resulting in considerable tensile strength. The central PU/Col I yarn layer is vital in promoting the tendinogenic differentiation of stem cells derived from tendons and increasing the expression of critical tendinogenic factors. The external PLLA/BG nanofiber membrane fosters the process of bone marrow mesenchymal stem cells differentiating into bone cells and enhances the expression of markers associated with bone formation. Our scaffold's biocompatibility and multi-functional design were confirmed through extensive in vivo evaluations, such as histological staining and biomechanical analyses. These assessments combined showed notable enhancements in ACL repair and healing. This study emphasizes the promise of multi-layered nanofiber scaffolds in orthopedic tissue engineering and also introduces new possibilities for the creation of improved materials for regenerating the tendon-bone interface.

11.
J Hazard Mater ; 476: 134987, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38908174

RESUMEN

Herein, in order to extract Ga3+ from acid fly ash leaching, we propose a functionalized Ti3C2Tx-based MXene composite aerogel adsorbent for Ga3+ adsorption. The prepared physicochemical dual-crosslinking network aerogel MPHG-40 possesses good Ga3+ adsorption performance (132.52 mg g-1) at the pH of 3 and Ga3+ initial concentration of 50 mg L-1 within 6 h. After five adsorption-desorption cycles, the material shows good mass retention and a 95.65 % retention of its initial adsorption capacity, compared to most reported adsorbents. The optimized adsorbent realized good selective adsorption of Ga3+ against Cu2+, Zn2+, Fe3+, and Al3+ in a simulated acid fly ash leaching with the selective coefficient of 8.63, 96.10, 4.49, and 28.30, respectively. The adsorption may comply with a combined mechanism of physical adsorption, electrostatic interactions, ion-exchange mechanism, and ligand chelation, dominated by chemical adsorption, as identified by theoretical calculations based on density functional theory and experimental data. The three-dimensional solid adsorbent constructed in this study provides a new strategy for selective adsorption of Ga3+, making it possible to be applied to solid waste utilization of fly ash.

12.
Nanoscale ; 16(20): 9861-9874, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38712977

RESUMEN

A guided bone regeneration (GBR) membrane can act as a barrier to prevent the invasion and interference from foreign soft tissues, promoting infiltration and proliferation of osteoblasts in the bone defect area. Herein, a composite scaffold with dual functions of osteogenesis and antibacterial effects was prepared for GBR. A polycaprolactone (PCL)/nano-hydroxyapatite (n-HA) aerogel produced by electrospinning and freeze-drying techniques was fabricated as the loose layer of the scaffold, while a PCL nanofiber membrane was used as the dense layer. Chitosan (CS) solution served as a middle layer to provide mechanical support and antibacterial effects between the two layers. Morphological results showed that the loose layer had a porous structure with n-HA successfully dispersed in the aerogels, while the dense layer possessed a sufficiently dense structure. In vitro antibacterial experiments illustrated that the CS solution in the middle layer stabilized the scaffold structure and endowed the scaffold with good antibacterial properties. The cytocompatibility results indicated that both fibroblasts and osteoblasts exhibited superior cell activity on the dense and loose layers, respectively. In particular, the dense layer made of nanofibers could work as a barrier layer to inhibit the infiltration of fibroblasts into the loose layer. In vitro osteogenesis analysis suggested that the PCL/n-HA aerogel could enhance the bone induction ability of bone mesenchymal stem cells, which was confirmed by the increased expression of the alkaline phosphatase activity. The loose structure facilitated the infiltration and migration of bone mesenchymal stem cells for better osteogenesis. In summary, such a composite scaffold exhibited excellent osteogenic and antibacterial properties as well as the barrier effect, thus holding promising potential for use as GBR materials.


Asunto(s)
Antibacterianos , Regeneración Ósea , Quitosano , Durapatita , Nanofibras , Osteoblastos , Osteogénesis , Poliésteres , Quitosano/química , Quitosano/farmacología , Durapatita/química , Durapatita/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Regeneración Ósea/efectos de los fármacos , Nanofibras/química , Poliésteres/química , Poliésteres/farmacología , Animales , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Ratones , Andamios del Tejido/química , Geles/química , Staphylococcus aureus/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/citología
13.
J Environ Manage ; 358: 120743, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38626484

RESUMEN

Coastal saline soil is an important reserve resource for arable land globally. Data from 10 years of continuous stubble return and subsoiling experiments have revealed that these two conservation tillage measures significantly improve cotton rhizosphere soil organic carbon sequestration in coastal saline soil. However, the contribution of microbial fixation of atmospheric carbon dioxide (CO2) has remained unclear. Here, metagenomics and metabolomics analyses were used to deeply explore the microbial CO2 fixation process in rhizosphere soil of coastal saline cotton fields under long-term stubble return and subsoiling. Metagenomics analysis showed that stubble return and subsoiling mainly optimized CO2 fixing microorganism (CFM) communities by increasing the abundance of Acidobacteria, Gemmatimonadetes, and Chloroflexi, and improving composition diversity. Conjoint metagenomics and metabolomics analyses investigated the effects of stubble return and subsoiling on the reverse tricarboxylic acid (rTCA) cycle. The conversion of citrate to oxaloacetate was inhibited in the citrate cleavage reaction of the rTCA cycle. More citrate was converted to acetyl-CoA, which enhanced the subsequent CO2 fixation process of acetyl-CoA conversion to pyruvate. In the rTCA cycle reductive carboxylation reaction from 2-oxoglutarate to isocitrate, synthesis of the oxalosuccinate intermediate product was inhibited, with strengthened CO2 fixation involving the direct conversion of 2-oxoglutarate to isocitrate. The collective results demonstrate that stubble return and subsoiling optimizes rhizosphere CFM communities by increasing microbial diversity, in turn increasing CO2 fixation by enhancing the utilization of rTCA and 3-hydroxypropionate/4-hydroxybutyrate cycles by CFMs. These events increase the microbial CO2 fixation in the cotton rhizosphere, thereby promoting the accumulation of microbial biomass, and ultimately improving rhizosphere soil organic carbon. This study clarifies the impact of conservation tillage measures on microbial CO2 fixation in cotton rhizosphere of coastal saline soil, and provides fundamental data for the improvement of carbon sequestration in saline soil in agricultural ecosystems.


Asunto(s)
Dióxido de Carbono , Secuestro de Carbono , Gossypium , Rizosfera , Microbiología del Suelo , Suelo , Dióxido de Carbono/metabolismo , Suelo/química , Carbono/metabolismo , Ciclo del Carbono
14.
iScience ; 27(3): 109270, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38487014

RESUMEN

Glioblastoma stem cells (GSCs) reside in hypoxic periarteriolar niches of glioblastoma micro-environment, however, the crosstalk of GSCs with macrophages on regulating tumor angiogenesis and progression are not fully elucidated. GSCs-derived exosomes (GSCs-exos) are essential mediators during tumor immune-microenvironment remodeling initiated by GSCs, resulting in M2 polarization of tumor-associated macrophages (TAMs) as we reported previously. Our data disclosed aberrant upregulation of miR-374b-3p in both clinical glioblastoma specimens and human cell lines of GSCs. MiR-374b-3p level was high in GSCs-exos and can be internalized by macrophages. Mechanistically, GSCs exosomal miR-374b-3p induced M2 polarization of macrophages by downregulating phosphatase and tensin expression, thereby promoting migration and tube formation of vascular endothelial cells after coculture with M2 macrophages. Cumulatively, these data indicated that GSCs exosomal miR-374b-3p can enhance tumor angiogenesis by inducing M2 polarization of macrophages, as well as promote malignant progression of glioblastoma. Targeting exosomal miR-374b-3p may serve as a potential target against glioblastoma.

15.
CNS Neurosci Ther ; 30(2): e14599, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38332576

RESUMEN

BACKGROUND: Glioblastoma is the most malignant primary brain tumor in adults. Temozolomide (TMZ) stands for the first-line chemotherapeutic agent against glioblastoma. Nevertheless, the therapeutic efficacy of TMZ appears to be remarkably limited, because of low cytotoxic efficiency against glioblastoma. Besides, various mechanical studies and the corresponding strategies fail to enhancing TMZ curative effect in clinical practice. Our previous studies have disclosed remodeling of glial cells by GSCs, but the roles of these transformed cells on promoting TMZ resistance have never been explored. METHODS: Exosomes were extracted from GSCs culture through standard centrifugation procedures, which can activate transformation of normal human astrocytes (NHAs) totumor-associated astrocytes (TAAs) for 3 days through detect the level of TGF-ß, CD44 and tenascin-C. The secretive protein level of ALKBH7 of TAAs was determined by ELISA kit. The protein level of APNG and ALKBH7 of GBM cells were determined by Western blot. Cell-based assays of ALKBH7 and APNG triggered drug resistance were performed through flow cytometric assay, Western blotting and colony formation assay respectively. A xenograft tumor model was applied to investigate the function of ALKBH7 in vivo. Finally, the effect of the ALKBH7/APNG signaling on TMZ resistance were evaluated by functional experiments. RESULTS: Exosomes derived from GSCs can activate transformation of normal human astrocytes (NHAs)to tumor-associated astrocytes (TAAs), as well as up-regulation of ALKBH7expression in TAAs. Besides, TAAs derived ALKBH7 can regulate APNG gene expression of GBM cells. After co-culturing with TAAs for 5 days, ALKBH7 and APNG expression in GBM cells were elevated. Furthermore, Knocking-down of APNG increased the inhibitory effect of TMZ on GBM cells survival. CONCLUSION: The present study illustrated a new mechanism of glioblastoma resistance to TMZ, which based on GSCs-exo educated TAAs delivering ALKBH7 to enhance APNG expression of GBM cells, which implied that targeting on ALKBH7/APNG regulation network may provide a new strategy of enhancing TMZ therapeutic effects against glioblastoma.


Asunto(s)
Neoplasias Encefálicas , Exosomas , Glioblastoma , Adulto , Humanos , Temozolomida/farmacología , Temozolomida/uso terapéutico , Glioblastoma/patología , Astrocitos/metabolismo , Exosomas/metabolismo , Células Madre/metabolismo , Neoplasias Encefálicas/genética , Resistencia a Antineoplásicos , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/uso terapéutico , Enzimas AlkB , Proteínas Mitocondriales
16.
Glia ; 72(5): 857-871, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38234042

RESUMEN

Tumor-associated astrocytes (TAAs) in the glioblastoma microenvironment play an important role in tumor development and malignant progression initiated by glioma stem cells (GSCs). In the current study, normal human astrocytes (NHAs) were cultured and continuously treated with GSC-derived exosomes (GSC-EXOs) induction to explore the mechanism by which GSCs affect astrocyte remodeling. This study revealed that GSC-EXOs can induce the transformation of NHAs into TAAs, with relatively swollen cell bodies and multiple extended processes. In addition, high proliferation, elevated resistance to temozolomide (TMZ), and increased expression of TAA-related markers (TGF-ß, CD44, and tenascin-C) were observed in the TAAs. Furthermore, GSC-derived exosomal miR-3065-5p could be delivered to NHAs, and miR-3065-5p levels increased significantly in TAAs, as verified by miRNA expression profile sequencing and Reverse transcription polymerase chain reaction. Overexpression of miR-3065-5p also enhanced NHA proliferation, elevated resistance to TMZ, and increased the expression levels of TAA-related markers. In addition, both GSC-EXO-induced and miR-3065-5p-overexpressing NHAs promoted tumorigenesis of GSCs in vivo. Discs Large Homolog 2 (DLG2, downregulated in glioblastoma) is a direct downstream target of miR-3065-5p in TAAs, and DLG2 overexpression could partially reverse the transformation of NHAs into TAAs. Collectively, these data demonstrate that GSC-EXOs induce the transformation of NHAs into TAAs via the miR-3065-5p/DLG2 signaling axis and that TAAs can further promote the tumorigenesis of GSCs. Thus, precisely blocking the interactions between astrocytes and GSCs via exosomes may be a novel strategy to inhibit glioblastoma development, but more in-depth mechanistic studies are still needed.


Asunto(s)
Exosomas , Glioblastoma , Glioma , MicroARNs , Humanos , Glioblastoma/patología , Astrocitos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Exosomas/metabolismo , Glioma/patología , Temozolomida/farmacología , Temozolomida/metabolismo , Células Madre Neoplásicas/metabolismo , Carcinogénesis/genética , Proliferación Celular , Microambiente Tumoral , Proteínas Supresoras de Tumor/metabolismo , Guanilato-Quinasas/metabolismo
17.
Int J Stroke ; 19(1): 40-49, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37477427

RESUMEN

OBJECTIVE: Hypotension is recognized as a common complication after carotid artery stenting, but its incidence and the risk factors associated with it are uncertain. Therefore, we performed a systematic review and meta-analysis to investigate and identify risk factors for hypotension after surgery. METHODS: We retrieved risk factors from eight databases for case-control and cross-sectional studies of hypotension after carotid artery stenting according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on 28 November 2022. Data were analyzed by using R4.2.1 and Review Manager 5.3. RESULTS: A total of 2843 samples were searched, and 17 publications were included in the analysis. The meta-analysis results showed that the incidence of hypotension after surgery was 28.6% (95% confidence interval [CI] (0.225, 0.347)). Age ⩾ 65 years (odds ratio [OR] = 4.55, 95% CI (2.50, 8.29), P < 0.00001), stenosis site (bulb) (OR = 4.41, 95% CI (2.50, 7.79), P < 0.00001), severe stenosis (OR = 3.56, 95% CI (1.62, 7.85), P = 0.002), stenosis proximity (⩽ 10 mm) to bifurcation (OR = 2.69, 95% CI (1.74, 4.15), P < 0.00001), calcified plaques (OR = 4.64, 95% CI (1.93, 11.14), P = 0.0006), post-balloon dilation (OR = 5.95, 95% CI (2.31, 15.31), P = 0.0002), bilateral carotid stenting (OR = 30.51, 95% CI (2.33, 399.89), P = 0.009), and intravenous fluid intake/mL on the first postoperative day (mean difference = 444.99, 95% CI (141.40, 748.59), P = 0.004) were risk factors for hypotension after surgery. CONCLUSIONS: A high incidence of hypotension was observed after carotid artery stenting. Age, stenosis site, severe stenosis, stenosis proximity to bifurcation, calcified plaques, post-balloon dilation, type of surgery, and intravenous fluid intake were identified as risk factors.


Asunto(s)
Estenosis Carotídea , Hipotensión , Accidente Cerebrovascular , Humanos , Anciano , Stents/efectos adversos , Estenosis Carotídea/cirugía , Estenosis Carotídea/complicaciones , Constricción Patológica , Incidencia , Estudios Transversales , Resultado del Tratamiento , Accidente Cerebrovascular/complicaciones , Hipotensión/epidemiología , Hipotensión/etiología , Factores de Riesgo , Arterias Carótidas
18.
J Clin Nurs ; 33(3): 1048-1061, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37828751

RESUMEN

AIMS: To establish a cognitive appraisal path model that examines the impact of stroke knowledge on stigma with the parallel mediating effects of negative and positive coping traits, as well as the moderating effects of family functioning. BACKGROUND: Stroke-related stigma, a 'mixture' of negative emotions involving internal criticism and external judgement, has been shown to impair patients' health outcomes. However, the specific factors underlying cognitive appraisals and their pathways remain unknown. DESIGN: A cross-sectional design. METHODS: The cross-sectional sample was from two stroke centres in China. Questionnaires were administered to collect sociodemographic data, stroke knowledge, coping traits, family functioning and stigma. Hierarchical regression models and the moderated parallel mediation model were constructed to analyse influencing pathways. The study adhered to the strengthening the reporting of observational studies in epidemiology guideline. RESULTS: All 144 samples reported stigma symptoms with a moderate-to-high standardising score. The best hierarchical regression model explains 55.5% of the variance in stigma. The parallel mediation model indicated that negative and positive coping traits co-mediating the association of stroke knowledge and stigma. After adding the family functioning as a moderator, the moderated parallel mediation model was confirmed with adequate fit indices. CONCLUSION: Among the cognitive appraisal factors affecting stroke-related stigma, stroke knowledge reduces stigma by modifying coping traits, while poor family functioning may serve as an opposing moderator. Notably, when family support is insufficient, enhanced stroke knowledge might paradoxically exacerbate the stigma. RELEVANCE TO CLINICAL PRACTICE: This study contributes knowledge on transforming health education and emphasises the pivotal roles of clinical nursing practitioners. In similar global contexts, the study highlights integrating health education, psychological counselling and family support to advance systematic nursing practices. PATIENT OR PUBLIC CONTRIBUTION: None.


Asunto(s)
Adaptación Psicológica , Habilidades de Afrontamiento , Humanos , Estudios Transversales , Pacientes , Cognición , Estigma Social
19.
PLoS One ; 18(11): e0289184, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38032972

RESUMEN

Transient electromagnetic Method (TEM) is an efficient geophysical detection technology suitable for detection of urban near-surface space. However, its detection results are well affected by the low resistance anomaly, which interferes with the interpretation of the inversion results. This article used finite element method to simulate the entire process of urban underground pipeline under TEM detection. The causes of interference and the degree of interference under different working conditions were analyzed. The results demonstrate that low resistance anomaly in magnetic field will caused electromagnetic energy absorption and resulting eddy current losses, which lead to a distortion of the primary magnetic field in the vicinity of the pipeline, and formation of a weak field zone beneath the pipeline. The size and shape of the shielding zone are affected by burial depth, transmitter coil diameter, and anomaly size. When the burial depth exceeds 10 times the diameter of the coil or pipeline, the shielding range stabilizes at 1.5-2 times the pipeline's transverse diameter. Moreover, when the pipeline's transverse diameter exceeds twice the transmitter coil diameter, the weak field zone beneath the pipeline will transform into a strong field zone, this is due to the refractive and reflective effects of the electromagnetic field. Finally, experiments were conducted and the inverted results was found to be larger than the actual pipeline diameter, with an error margin similar to that explained by the simulation. These results have implications for high accuracy detecting underground pipelines in urban areas.


Asunto(s)
Campos Electromagnéticos , Campos Magnéticos , Simulación por Computador
20.
Front Comput Neurosci ; 17: 1211096, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37841676

RESUMEN

Introduction: The automatic precision detection technology based on electroencephalography (EEG) is essential in epilepsy studies. It can provide objective proof for epilepsy diagnosis, treatment, and evaluation, thus helping doctors improve treatment efficiency. At present, the normal and acute phases of epilepsy can be well identified through EEG analysis, but distinguishing between the normal and chronic phases is still tricky. Methods: In this paper, five popular complexity indicators of EEG signal, including approximate entropy, sample entropy, permutation entropy, fuzzy entropy and Kolmogorov complexity, are computed from rat hippocampi to characterize the normal, acute, and chronic phases during epileptogenesis. Results of one-way ANOVA and principal component analysis both show that utilizing complexity features, we are able to easily identify differences between normal, acute, and chronic phases. We also propose an innovative framework for epilepsy detection based on graph convolutional neural network (GCNN) using multi-channel EEG complexity as input. Results: Combining information of five complexity measures at eight channels, our GCNN model demonstrate superior ability in recognizing the normal, acute, and chronic phases. Experiments results show that our GCNN model reached the high prediction accuracy above 98% and F1 score above 97% among these three phases for each individual rat. Discussion: Our research practice based on real data shows that EEG complexity characteristics are of great significance for recognizing different stages of epilepsy.

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