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1.
Medicine (Baltimore) ; 103(33): e39266, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39151510

RESUMEN

RATIONALE: Congenital sensorineural hearing loss is a significant global health issue, primarily driven by genetic factors, such as mutations in the GJB2 gene. This report presents a Chinese girl with congenital deafness and a novel mutation of the GJB2 gene. PATIENT CONCERNS: A newborn Chinese girl exhibited signs of congenital deafness. DIAGNOSIS: Congenital deafness was confirmed through comprehensive newborn hearing screenings that included otologic, audiologic, and physical examinations. Genetic analysis revealed a compound heterozygous mutation involving c.188delT and c.235delC in the GJB2 gene, indicating a genetic basis for her hearing loss. INTERVENTIONS: The patient underwent cochlear implantation, which resulted in stable auditory outcomes. OUTCOMES: Despite follow-up difficulties, stable auditory outcomes were achieved post-cochlear implantation, highlighting the potential efficacy of this intervention in GJB2-related hearing loss. LESSONS: This case study enriches our understanding of GJB2 mutations and underscores the critical role of genetic testing in diagnosing congenital sensorineural hearing loss. It emphasizes the necessity for early intervention and sustained interdisciplinary care to enhance the quality of life for patients with genetic hearing impairment.


Asunto(s)
Conexina 26 , Conexinas , Pérdida Auditiva Sensorineural , Humanos , Femenino , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/diagnóstico , Conexinas/genética , Recién Nacido , Mutación , Implantación Coclear , China , Pueblo Asiatico/genética , Pueblos del Este de Asia
2.
Front Pharmacol ; 15: 1398294, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38860174

RESUMEN

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestines that can significantly impact quality of life and lead to various complications. Currently, 5-aminosalicylic acid derivatives, corticosteroids, immunosuppressants, and biologics are the major treatment strategies for UC, but their limitations have raised concerns. Atractylenolides (ATs), sesquiterpene metabolites found in Atractylodes macrocephala Koidz., have shown promising effects in treating UC by exerting immune barrier modulation, alleviating oxidative stress, gut microbiota regulation, improving mitochondrial dysfunction and repairing the intestinal barrier. Furthermore, ATs have been shown to possess remarkable anti-fibrosis, anti-thrombus, anti-angiogenesis and anti-cancer. These findings suggest that ATs hold important potential in treating UC and its complications. Therefore, this review systematically summarizes the efficacy and potential mechanisms of ATs in treating UC and its complications, providing the latest insights for further research and clinical applications.

3.
J Med Chem ; 67(13): 10967-10985, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38943600

RESUMEN

Antibody-based targeted therapy in cancer faces a challenge due to uneven antibody distribution in solid tumors, hindering effective drug delivery. We addressed this by developing peptide mimetics with nanomolar-range affinity for Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using computational methods. These peptides showed both specific targeting and deep penetration in vitro and in vivo. Additionally, we created peptide-drug conjugates (PDCs) by linking targeting peptides to toxin drugs via various linkers and enhancing their in vivo half-life with fatty side chains for albumin binding. The antitumor candidate II-3 displayed exceptional affinity (KD = 1.72 × 10-9 M), internalization efficiency, anticancer potency (IC50 = 0.015 ± 0.002 µM), and pharmacokinetics (t1/2 = 2.6 h), showcasing a rational approach for designing PDCs with favorable tissue distribution and strong tumor penetration.


Asunto(s)
Péptidos , Humanos , Animales , Péptidos/química , Péptidos/farmacología , Ratones , Línea Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Inmunoconjugados/química , Inmunoconjugados/farmacología , Inmunoconjugados/farmacocinética , Inmunoconjugados/uso terapéutico , Neoplasias/tratamiento farmacológico , Femenino , Ratones Endogámicos BALB C
4.
Front Pharmacol ; 15: 1349259, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590641

RESUMEN

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis of the affected joints. Total glucosides of paeony (TGP) capsules have been widely used clinically for the treatment of RA with good efficacy and safety. However, its effect on inflammatory cytokines remains unclear. Objectives: This study aimed to summarize the effect of TGP on the expression level of serum inflammatory cytokines in RA animal models and its potential mechanisms. Methods: Six databases were searched up to 14 August 2023, relevant animal experiment studies were screened, data were extracted, and the SYRCLE animal experiment bias risk assessment tool was used for risk assessment. Results: A total of 24 studies were included, including 581 animals. Results showed that compared with the model control group, TGP decreased the levels of TNF-α, IL-1ß, IL-6, and PGE2 and increased the levels of TGF-ß1 after 1-2 weeks of intervention, decreased the levels of TNF-α, IL-1ß, IL-6, IL-2, IL-17, IL-17α, IL-21, VEGF, IFN-γ and PGE2 and increased the levels of IL-10 and IL-4 after 3-4 weeks of intervention, decreased the levels of TNF-α, IL-6, IL-17α and increased the level of IL-10 after 8 weeks of intervention. There was no significant difference in the effects of TGP on the levels of IL-10, IL-17, and IFN-γ after 1-2 weeks of intervention and IL-1 and TGF-ß1 after 3-4 weeks of intervention. Conclusion: In summary, based on the existing studies, this study found that compared with the control group of the RA animal model, TGP can reduce the levels of serum pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 and increase the levels of serum anti-inflammatory cytokines such as IL-10, exerting an anti-inflammatory effect by regulating and improving the levels of inflammatory cytokines, and thus alleviating the disease. Given the low quality of the included studies and the lack of sufficient evidence, more high-quality studies are still needed to validate the results of this study.

5.
Health Inf Sci Syst ; 12(1): 21, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38464463

RESUMEN

Cancer is a complex gene mutation disease that derives from the accumulation of mutations during somatic cell evolution. With the advent of high-throughput technology, a large amount of omics data has been generated, and how to find cancer-related driver genes from a large number of omics data is a challenge. In the early stage, the researchers developed many frequency-based driver genes identification methods, but they could not identify driver genes with low mutation rates well. Afterwards, researchers developed network-based methods by fusing multi-omics data, but they rarely considered the connection among features. In this paper, after analyzing a large number of methods for integrating multi-omics data, a hierarchical weak consensus model for fusing multiple features is proposed according to the connection among features. By analyzing the connection between PPI network and co-mutation hypergraph network, this paper firstly proposes a new topological feature, called co-mutation clustering coefficient (CMCC). Then, a hierarchical weak consensus model is used to integrate CMCC, mRNA and miRNA differential expression scores, and a new driver genes identification method HWC is proposed. In this paper, the HWC method and current 7 state-of-the-art methods are compared on three types of cancers. The comparison results show that HWC has the best identification performance in statistical evaluation index, functional consistency and the partial area under ROC curve. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-024-00279-6.

6.
Front Immunol ; 15: 1250884, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38482018

RESUMEN

Fibroblast-like synoviocytes (FLS) are important components of the synovial membrane. They can contribute to joint damage through crosstalk with inflammatory cells and direct actions on tissue damage pathways in rheumatoid arthritis (RA). Recent evidence suggests that, compared with FLS in normal synovial tissue, FLS in RA synovial tissue exhibits significant differences in metabolism. Recent metabolomic studies have demonstrated that metabolic changes, including those in glucose, lipid, and amino acid metabolism, exist before synovitis onset. These changes may be a result of increased biosynthesis and energy requirements during the early phases of the disease. Activated T cells and some cytokines contribute to the conversion of FLS into cells with metabolic abnormalities and pro-inflammatory phenotypes. This conversion may be one of the potential mechanisms behind altered FLS metabolism. Targeting metabolism can inhibit FLS proliferation, providing relief to patients with RA. In this review, we aimed to summarize the evidence of metabolic changes in FLS in RA, analyze the mechanisms of these metabolic alterations, and assess their effect on RA phenotype. Finally, we aimed to summarize the advances and challenges faced in targeting FLS metabolism as a promising therapeutic strategy for RA in the future.


Asunto(s)
Artritis Reumatoide , Sinoviocitos , Sinovitis , Humanos , Sinoviocitos/metabolismo , Artritis Reumatoide/metabolismo , Membrana Sinovial/metabolismo , Sinovitis/metabolismo , Fibroblastos/metabolismo
7.
IEEE Trans Pattern Anal Mach Intell ; 46(6): 4331-4347, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38265906

RESUMEN

Individuals have unique facial expression and head pose styles that reflect their personalized speaking styles. Existing one-shot talking head methods cannot capture such personalized characteristics and therefore fail to produce diverse speaking styles in the final videos. To address this challenge, we propose a one-shot style-controllable talking face generation method that can obtain speaking styles from reference speaking videos and drive the one-shot portrait to speak with the reference speaking styles and another piece of audio. Our method aims to synthesize the style-controllable coefficients of a 3D Morphable Model (3DMM), including facial expressions and head movements, in a unified framework. Specifically, the proposed framework first leverages a style encoder to extract the desired speaking styles from the reference videos and transform them into style codes. Then, the framework uses a style-aware decoder to synthesize the coefficients of 3DMM from the audio input and style codes. During decoding, our framework adopts a two-branch architecture, which generates the stylized facial expression coefficients and stylized head movement coefficients, respectively. After obtaining the coefficients of 3DMM, an image renderer renders the expression coefficients into a specific person's talking-head video. Extensive experiments demonstrate that our method generates visually authentic talking head videos with diverse speaking styles from only one portrait image and an audio clip.


Asunto(s)
Expresión Facial , Movimientos de la Cabeza , Habla , Grabación en Video , Humanos , Habla/fisiología , Movimientos de la Cabeza/fisiología , Algoritmos , Cabeza , Imagenología Tridimensional/métodos , Cara/anatomía & histología , Procesamiento de Imagen Asistido por Computador/métodos
8.
ACS Sens ; 9(1): 126-138, 2024 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-38170944

RESUMEN

Cardiac monitoring after heart surgeries is crucial for health maintenance and detecting postoperative complications early. However, current methods like rigid implants have limitations, as they require performing second complex surgeries for removal, increasing infection and inflammation risks, thus prompting research for improved sensing monitoring technologies. Herein, we introduce a nanosensor platform that is biodegradable, biocompatible, and integrated with multifunctions, suitable for use as implants for cardiac monitoring. The device has two electrochemical biosensors for sensing lactic acid and pH as well as a pressure sensor and a chemiresistor array for detecting volatile organic compounds. Its biocompatibility with myocytes has been tested in vitro, and its biodegradability and sensing function have been proven with ex vivo experiments using a three-dimensional (3D)-printed heart model and 3D-printed cardiac tissue patches. Moreover, an artificial intelligence-based predictive model was designed to fuse sensor data for more precise health assessment, making it a suitable candidate for clinical use. This sensing platform promises impactful applications in the realm of cardiac patient care, laying the foundation for advanced life-saving developments.


Asunto(s)
Técnicas Biosensibles , Dispositivos Electrónicos Vestibles , Humanos , Inteligencia Artificial , Prótesis e Implantes , Monitoreo Fisiológico
9.
Commun Chem ; 7(1): 2, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172516

RESUMEN

The integration of dual asymmetric catalysis is highly beneficial for the synthesis of organic molecules with multiple stereocenters. However, two major issues that need to be addressed are the intrinsic deactivation of dual-species and the extrinsic conflict of reaction conditions. To overcome these concerns, we have utilized the compartmental and thermoresponsive properties of poly(N-isopropylacrylamide) (PNIPAM) to develop a cross-linked PNIPAM-hydrogel-supported bifunctional catalyst. This catalyst is designed with Rh(diene) species situated on the outer surface and Ru(diamine) species positioned within the interior of the hydrogel. The compartmental function of PNIPAM in the middle overcomes intrinsic mutual deactivations between the dual-species. The thermoresponsive nature of PNIPAM allows for precise control of catalytic pathways in resolving external conflicts by controlling the reaction switching between an Rh-catalyzed enantioselective 1,4-addition at 50°C and a Ru-catalyzed asymmetric transfer hydrogenation (ATH) at 25°C. As we envisioned, this sequential 1,4-addition/reduction dual enantioselective cascade reaction achieves a transformation from incompatibility to compatibility, resulting in direct access to γ-substituted cyclic alcohols with dual stereocenters in high yields and enantio/diastereoselectivities. Mechanistic investigation reveals a reversible temperature transition between 50°C and 25°C, ensuring a cascade process comprising a 1,4-addition followed by the ATH process.

10.
ACS Appl Mater Interfaces ; 16(5): 6198-6207, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38276960

RESUMEN

Enhancing the durability and functionality of existing materials through sustainable pathways and appropriate structural design represents a time- and cost-effective strategy for the development of advanced wearable devices. Herein, a facile graphene oxide (GO) modification method via the hydroxyl-yne click reaction is present for the first time. By the click coupling between propiolate esters and hydroxyl groups on GO under mild conditions, various functional molecules are successfully grafted onto the GO. The modified GO is characterized by FTIR, XRD, TGA, XPS, and contact angle, proving significantly improved dispersibility in various solvents. Besides the high efficiency, high selectivity, and mild reaction conditions, this method is highly practical and accessible, avoiding the need for prefunctionalizations, metals, or toxic reagents. Subsequently, a rGO-PDMS sponge-based piezoresistive sensor developed by modified GO-P2 as the sensitive material exhibits impressive performance: high sensitivity (335 kPa-1, 0.8-150 kPa), wide linear range (>500 kPa), low detection limit (0.8 kPa), and long-lasting durability (>5000 cycles). Various practical applications have been demonstrated, including body joint movement recognition and real-time monitoring of subtle movements. These results prove the practicality of the methodology and make the rGO-PDMS sponge-based pressure sensor a real candidate for a wide array of wearable applications.

11.
Eur J Med Chem ; 264: 116032, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38104378

RESUMEN

Human epidermal growth factor receptor 2 (HER2) represents an ideal target for antibody drug development, abnormal expression of the HER2 gene is associated with multiple tumor types. Pertuzumab, as the first monoclonal antibody inhibitor of HER2 dimerization, has been FDA-approved for HER2-positive patients. In order to enhance the activity of HER2-targeted peptide-drug conjugates (PDCs) developed based on pertuzumab, a novel class of conjugates 1-9 was designed and synthesized by fusing the N-terminal peptide sequence of the second mitochondria-derived activator of caspases (SMAC) with P1, followed by conjugation with CPT molecules. Compound 4 exhibited excellent in vitro anti-tumor activity across the three HER2-positive cell lines, comparable to the activity of CPT. Apoptosis induction assays indicated that the synergistic effect of the SMAC sequence enhanced the pro-apoptotic activity of the conjugate. Western Blot analysis and Caspase activity studies validated the mechanism through which SMAC peptides, in synergy with CPT, enhance the activity of PDCs. In vivo studies demonstrated that compound 4 possesses superior anti-tumor activity compared to CPT and can effectively mitigate potential renal toxicity associated with free SMAC peptides. In conclusion, conjugate 4 exhibited excellent anti-tumor activity both in vitro and in vivo, offering potential for further development as a novel peptide-conjugated drug.


Asunto(s)
Caspasas , Receptor ErbB-2 , Humanos , Receptor ErbB-2/metabolismo , Caspasas/metabolismo , Muerte Celular , Péptidos/farmacología , Anticuerpos Monoclonales , Línea Celular Tumoral
12.
Health Inf Sci Syst ; 11(1): 55, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37981988

RESUMEN

Essential proteins play a vital role in development and reproduction of cells. The identification of essential proteins helps to understand the basic survival of cells. Due to time-consuming, costly and inefficient with biological experimental methods for discovering essential proteins, computational methods have gained increasing attention. In the initial stage, essential proteins are mainly identified by the centralities based on protein-protein interaction (PPI) networks, which limit their identification rate due to many false positives in PPI networks. In this study, a purified PPI network is firstly introduced to reduce the impact of false positives in the PPI network. Secondly, by analyzing the similarity relationship between a protein and its neighbors in the PPI network, a new centrality called neighborhood similarity centrality (NSC) is proposed. Thirdly, based on the subcellular localization and orthologous data, the protein subcellular localization score and ortholog score are calculated, respectively. Fourthly, by analyzing a large number of methods based on multi-feature fusion, it is found that there is a special relationship among features, which is called dominance relationship, then, a novel model based on dominance relationship is proposed. Finally, NSC, subcellular localization score, and ortholog score are fused by the dominance relationship model, and a new method called NSO is proposed. In order to verify the performance of NSO, the seven representative methods (ION, NCCO, E_POC, SON, JDC, PeC, WDC) are compared on yeast datasets. The experimental results show that the NSO method has higher identification rate than other methods.

13.
Nanomaterials (Basel) ; 13(20)2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37887929

RESUMEN

When designing nano-structured metamaterials with an iterative optimization method, a fast deep learning solver is desirable to replace a time-consuming numerical solver, and the related issue of data shift is a subtle yet easily overlooked challenge. In this work, we explore the data shift challenge in an AI-based electromagnetic solver and present innovative solutions. Using a one-dimensional grating coupler as a case study, we demonstrate the presence of data shift through the probability density method and principal component analysis, and show the degradation of neural network performance through experiments dealing with data affected by data shift. We propose three effective strategies to mitigate the effects of data shift: mixed training, adding multi-head attention, and a comprehensive approach that combines both. The experimental results validate the efficacy of these approaches in addressing data shift. Specifically, the combination of mixed training and multi-head attention significantly reduces the mean absolute error, by approximately 36%, when applied to data affected by data shift. Our work provides crucial insights and guidance for AI-based electromagnetic solvers in the optimal design of nano-structured metamaterials.

14.
Nano Lett ; 23(22): 10441-10448, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37818981

RESUMEN

The low performance of sensors based on an all-dielectric metasurface limits their application compared to metallic counterparts. Here, for the first time, an all-dielectric BIC (bound states in the continuum) metasurface is employed for highly sensitive phase interrogation refractive index sensing. The proposed sensor is well analyzed, fabricated, and characterized. Experimentally, a high-performance BIC-based microfluidic sensing chip with a Q factor of 1200 is achieved by introducing symmetry breaking. A refractive index sensor with high figure of merit of 418 RIU-1 is demonstrated, which is beneficial to the phase interrogation. Notably, we measure a record phase interrogation sensitivity of 2.7 × 104 deg/RIU to the refractive index, thus enabling the all-dielectric BIC to rival the refractive index detection capabilities of metal-based sensors such as surface plasmon resonance. This scheme establishes a pivotal role of the all-dielectric metasurface in the field of ultrahigh sensitivity sensors and opens possibilities for trace detection in biochemical analysis and environment monitoring.

15.
Environ Sci Pollut Res Int ; 30(32): 78521-78536, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37271788

RESUMEN

The effect of polydopamine (PDA) modification on aminated Fe3O4 nanoparticles (Fe3O4-NH2)/graphite oxide (GO)/ß-cyclodextrin polymer cross-linked by citric acid (CDP-CA) composites were studied for the removal of a cationic dye (methylene blue, MB) and an anionic dye (Congo red, CR) from waters. The micro-structural and magnetic characterizations confirmed the successful preparation of Fe3O4-NH2/GO/CDP-CA and PDA/Fe3O4-NH2/GO/CDP-CA composites. The maximum MB and CR adsorption capacities of Fe3O4-NH2/GO/CDP-CA were 75 mg/g and 104 mg/g, respectively, while the corresponding amounts for PDA/Fe3O4-NH2/GO/CDP-CA composite were 195 mg/g and 64 mg/g, respectively. The dye sorption behaviors of these two composites were explained by their corresponding surface-charged properties according to the measured zeta potential results. Moreover, the high saturation magnetizations and the stable dye removal rate in the adsorption-desorption cycles indicated the good recyclability and reusability of the fabricated composites.


Asunto(s)
Ciclodextrinas , Grafito , Grafito/química , Ácido Cítrico , Óxidos/química , Adsorción , Fenómenos Magnéticos
16.
J Cardiothorac Surg ; 18(1): 174, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37161427

RESUMEN

BACKGROUND: Double aortic arch (DAA) combined with descending aortic arch dissection (DAAD) in adults is a rare aorta vascular disease. Due to the abnormal anatomy of the double arch and arch vessels, the clinical symptoms and surgical methods differ from those of typical aortic dissection. METHODS: This study was retrospective analysis of a case series involving three patients (mean age, 47.3 years) with DAA combined DAAD underwent total arch replacement or hybrid aortic repair from September 2010 to June 2019. The patients' demographics, initial symptoms, comorbidities, surgical procedures, and outcomes are summarized. RESULTS: Total arch replacement plus frozen stent implantation under deep hypothermic circulatory arrest was performed for 2 patients, one of them developed disseminated intravascular coagulation and multiple organ failure postoperatively. Case 3 underwent a hybrid procedure with left subclavian artery revascularization and thoracic endovascular aortic repair. The symptoms of hoarseness and dysphagia were obviously improved during the follow up. CONCLUSION: In addition to typical sudden chest and back pain, patients with DAA and DAAD may have hoarseness and dysphagia. Based on the development of DAA, total arch replacement or hybrid surgery may be is an optional treatment.


Asunto(s)
Enfermedades de la Aorta , Trastornos de Deglución , Disección de la Aorta Torácica , Anillo Vascular , Humanos , Adulto , Persona de Mediana Edad , Ronquera , Estudios Retrospectivos , Enfermedades de la Aorta/cirugía
17.
Molecules ; 28(10)2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37241985

RESUMEN

A niobium-doped HZSM-5 (H[Nb]ZSM-5) was prepared by a hydrothermal synthesis method. The morphology, phase structure, composition, pore structure, and acid content of the catalyst were characterized using a series of analysis techniques such as scanning electron microscope (SEM), energy-dispersive X-ray (EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), nitrogen adsorption-desorption, and temperature programmed desorption measurements (NH3-TPD). The H[Nb]ZSM-5 catalyst fully remained within the crystal framework and pore structure of HZSM-5. Meanwhile, introduction of niobium (V) endowed the catalyst with both Lewis acid and Bronsted acid sites. Catalytic fast pyrolysis (CFP) of alkali lignin was carried out through a pyrolysis and gas chromatography-mass spectrometry (Py-GC/MS) at 650 °C and atmospheric pressure. The results indicated that H[Nb]ZSM-5 can efficiently and selectively convert lignin into monoaromatic hydrocarbons (MAHs), compared to the control HZSM-5. Catalyzed by H[Nb]ZSM-5, the content of MAHs and aliphatic hydrocarbons reached 43.4% and 20.8%, respectively; while under the catalysis of HZSM-5, these values were 35.5% and 3.2%, respectively. H[Nb]ZSM-5 remarkably lowered the phenol content to approximately 2.8%, which is far lower than the content (24.9%) obtained under HZSM-5 catalysis.

18.
Transl Res ; 260: 1-16, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37220836

RESUMEN

Neointimal hyperplasia is a major clinical complication of coronary artery bypass graft and percutaneous coronary intervention. Smooth muscle cells (SMCs) play a vital roles in neointimal hyperplasia development and undergo complex phenotype switching. Previous studies have linked glucose transporter member 10(Glut10) to the phenotypic transformation of SMCs. In this research, we reported that Glut10 helps maintain the contractile phenotype of SMCs. The Glut10-TET2/3 signaling axis can arrest neointimal hyperplasia progression by improving mitochondrial function via promotion of mtDNA demethylation in SMCs. Glut10 is significantly downregulated in both human and mouse restenotic arteries. Global Glut10 deletion or SMC-specific Glut10 ablation in the carotid artery of mice accelerated neointimal hyperplasia, while Glut10 overexpression in the carotid artery triggered the opposite effects. All of these changes were accompanied by a significant increase in vascular SMCs migration and proliferation. Mechanistically, Glut10 is expressed primarily in the mitochondria after platelet-derived growth factor-BB (PDGF-BB) treatment. Glut10 ablation induced a reduction in ascorbic acid (VitC) concentrations in mitochondria and mitochondrial DNA (mtDNA) hypermethylation by decreasing the activity and expression of the Ten-eleven translocation (TET) protein family. We also observed that Glut10 deficiency aggravated mitochondrial dysfunction and decreased the adenosinetriphosphate (ATP) content and the oxygen consumption rate, which also caused SMCs to switch their phenotype from contractile to synthetic phenotype. Furthermore, mitochondria-specific TET family inhibition partially reversed these effects. These results suggested that Glut10 helps maintain the contractile phenotype of SMCs. The Glut10-TET2/3 signaling axis can arrest neointimal hyperplasia progression by improving mitochondrial function via the promotion of mtDNA demethylation in SMCs.


Asunto(s)
ADN Mitocondrial , Neointima , Animales , Humanos , Ratones , Arterias Carótidas/patología , Movimiento Celular , Proliferación Celular , Células Cultivadas , Desmetilación , ADN Mitocondrial/genética , Hiperplasia/metabolismo , Hiperplasia/patología , Mitocondrias/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Neointima/genética , Neointima/metabolismo , Neointima/patología
19.
Heliyon ; 9(3): e13836, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36873535

RESUMEN

Background: Glucose transporter 10 (GLUT10) is encoded by the SLC2A10 gene. Our recent investigations have shown that GLUT10 is not only involved in glucose metabolism but also involved in the body's immune response to cancer cells. However, the role of GLUT10 in tumor prognosis and in tumor immunity has not been reported. Methods: We knocked down SLC2A10 and performed transcriptome sequencing to analyse the biological function of GLUT10 and found that GLUT10 may be involved in immune signaling. Then, we studied the expression level of SLC2A10 in cancers by the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We also evaluated the prognostic potential of SLC2A10 in different cancers using the Kaplan‒Meier plotter database and PrognoScan online software. The correlations between SLC2A10 expression and immune infiltrates were analysed by TIMER. In addition, correlations between SLC2A10 expression and gene marker sets of immune infiltrates were analysed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). Immunofluorescence staining of cyclooxygenase-2 (COX-2) and GLUT10 in lung cancer tissue and adjacent tissue was performed to confirm our findings from the database research. Results: Knocking down SLC2A10 widely activated immune and inflammatory signaling. SLC2A10 was abnormally expressed in several tumors. The expression level of SLC2A10 was closely correlated with cancer prognosis. Low SLC2A10 expression was related to poorer prognosis and increased malignancy of lung cancer. Lung cancer patients with low expression of SLC2A10 have a much shorter median survival time than patients with high expression of SLC2A10. SLC2A10 expression is closely related to the infiltration of different types of immune cells, particularly macrophages. Both database research and lung cancer sample research revealed that GLUT10 might modulate immune cell infiltration via the COX-2 pathway. Conclusions: By transcriptome experiments, database studies, and human sample studies, we found that GLUT10 is a new immune signaling molecule involved in tumor immunity, especially in the immune cell infiltration of lung adenocarcinoma (LUAD). GLUT10 may modulate the immune cell infiltration of LUAD via the COX-2 pathway.

20.
Comput Math Methods Med ; 2023: 6304047, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36873788

RESUMEN

Background: The Blumgart anastomosis (BA) is one of the safest anastomoses for pancreatic stump reconstruction. The incidence of postoperative pancreatic fistula (POPF) and postoperative complications is low. However, how to make laparoscopic pancreaticoenterostomy easier and safer is still a topic to be discussed. Methods: The data of patients who underwent laparoscopic pancreaticoduodenectomy (PD) from April 2014 to December 2019 were analyzed retrospectively. Results: Half-invagination anastomosis was performed in 20 cases (HI group), and the Cattell-Warren anastomosis was carried out in 26 cases (CW group). The amount of intraoperative bleeding, operation time, and postoperative catheterization time in the HI group was significantly less than those in the CW group. Besides, the number of patients at the Clavien-Dindo grade III and above in the HI group was significantly less than that in the control group. Moreover, the incidence of POPF in the HI group was significantly lower than that in the CW group. Furthermore, fistula risk score (FRS) analysis showed that there was no high-risk group, and the highest risk in the medium-risk group was pancreatic leakage. In addition, the incidence of pancreatic leakage in the HI group and CW group was 7.7% and 46.67%, respectively, while the incidence of pancreatic leakage in the HI group was significantly lower than that in the CW group. Conclusions: The half-invagination pancreaticoenterostomy based on the Blumgart anastomosis should have good applicability under laparoscopy and could effectively reduce the incidence of postoperative pancreatic leakage.


Asunto(s)
Laparoscopía , Pancreaticoduodenectomía , Humanos , Anastomosis Quirúrgica , Incidencia , Estudios Retrospectivos
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