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Identifying the antibacterial mechanisms of elemental silver at the nanoscale remains a significant challenge due to the intertwining behaviors between the particles and their released ions. The open question is which of the above factor dominate the antibacterial behaviors when silver nanoparticles (Ag NPs) with different sizes. Considering the high reactivity of Ag NPs, prior research has primarily concentrated on coated particles, which inevitably hinder the release of Ag+ ions due to additional chemical agents. In this study, we synthesized various Ag NPs, both coated and uncoated, using the laser ablation in liquids (LAL) technique. By analyzing both the changes in particle size and Ag+ ions release, the impacts of various Ag NPs on the cellular activity and morphological changes of gram-negative (E. coil) and gram-positive (S. aureus) bacteria were evaluated. Our findings revealed that for uncoated Ag NPs, smaller particles exhibited greater ions release efficiency and enhanced antibacterial efficacy. Specifically, particles approximately 1.5â¯nm in size released up to 55â¯% of their Ag+ ions within 4â¯h, significantly inhibiting bacterial growth. Additionally, larger particles tended to aggregate on the bacterial cell membrane surface, whereas smaller particles were more likely to be internalized by the bacteria. Notably, treatment with smaller Ag NPs led to more pronounced bacterial morphological changes and elevated levels of intracellular reactive oxygen species (ROS). We proposed that the bactericidal activity of Ag NPs stems from the synergistic effect between particle-cell interaction and the ionic silver, which is dependent on the crucial parameter of particle size.
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The efficacy of ulcerative colitis (UC) therapy is closely connected to the composition of gut microbiota in the gastrointestinal tract. Prebiotic-based nanoparticles (NPs) provide a more precise approach to alleviate UC via modulating gut microbiota dysbiosis. The present study develops an efficient prebiotic-based colon-targeted drug delivery system (PCDDS) by using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a prebiotic shell, with the anti-inflammatory drug sulfasalazine (SAS) loaded into a poly(lactic-co-glycolic acid) (PLGA) core to construct SAS@PLGA-Csn-Pcn NPs. Then, we examine its characterization, cellular uptake, and in vivo therapeutic efficacy. The results of our study indicate that the Pcn/Csn shell confers efficient pH-sensitivity properties. The gut microbiota-secreted pectinase serves as the trigger agent for Pcn/Csn shell degradation, and the resulting Pcn oligosaccharides possess a substantial prebiotic property. Meanwhile, the formed PCDDSs exhibit robust biodistribution and accumulation in the colon tissue, rapid cellular uptake, efficient in vivo therapeutic efficacy, and modulation of gut microbiota dysbiosis in a mouse colitis model. Collectively, our synthetic PCDDSs demonstrate a promising and synergistic strategy for UC therapy.
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l-2-Hydroxyglutarate (l-2-HG) has been regarded as a tumor metabolite, and it plays a crucial role in adaptation of tumor cells to hypoxic conditions. However, the role of l-2-HG in tumor radioresistance and the underlying mechanism have not yet been revealed. Here, we found that l-2-HG exhibited to have radioresistance effect on U87 human glioblastoma cells, which could reduce DNA damage and apoptosis caused by irradiation, promote cell proliferation and migration, and impair G2/M phase arrest. Mechanistically, l-2-HG upregulated the protein level of hypoxia-inducible factor-1α (HIF-1α) and the expression levels of HIF-1α downstream target genes. The knockdown of l-2-hydroxyglutarate dehydrogenase (L2HGDH) gene promoted the tumor growth and proliferation of U87 cells in nude mice by increasing HIF-1α expression level in vivo. In addition, the low expression level of L2HGDH gene was correlated with the short survival of patients with glioma or kidney cancer. In conclusion, our study revealed the role and mechanism of l-2-HG in tumor radioresistance and may provide a new perspective for overcoming tumor radioresistance and broaden our comprehension of the role of metabolites in tumor microenvironment.
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The management of dysfunctional intestinal epithelium by promoting mucosal healing and modulating the gut microbiota represents a novel therapeutic strategy for inflammatory bowel disease (IBD). As a convenient and well-tolerated method of drug delivery, intrarectal administration may represent a viable alternative to oral administration for the treatment of IBD. Here, a biomimetic supramolecular assembly of hyaluronic acid (HA) and ß-cyclodextrin (HA-ß-CD) for the delivery of the C domain peptide of insulin-like growth factor-1 (IGF-1C), which gradually releases IGF-1C, is developed. It is identified that the supramolecular assembly of HA-ß-CD enhances the stability and prolongs the release of IGF-1C. Furthermore, this biomimetic supramolecular assembly potently inhibits the inflammatory response, thereby restoring intestinal barrier integrity. Following HA-ß-CD-IGF-1C administration, 16S rDNA sequencing reveals a significant increase in the abundance of the probiotic Akkermansia, suggesting enhanced intestinal microbiome homeostasis. In conclusion, the findings demonstrate the promise of the HA-based mimicking peptide delivery platform as a therapeutic approach for IBD. This biomimetic supramolecular assembly effectively ameliorates intestinal barrier function and intestinal microbiome homeostasis, suggesting its potential for treating IBD.
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Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatic disease. The incidence and prevalence of NAFLD have increased greatly in recent years, and there is still a lack of effective drugs. Autophagy plays an important role in promoting liver metabolism and maintaining liver homeostasis, and defects in autophagy levels are considered to be related to the development of NAFLD. However, the molecular mechanisms of autophagy in NAFLD still remain unknown. In this study, we identified 6 autophagy-associated hub genes using gene expression profiles obtained from the GSE48452 and GSE89632 datasets. Biomarkers were screened according to gene significance (GS) and module membership (MM) using weighted gene co-expression network analysis (WGCNA), and the immune infiltration landscape of the liver in NAFLD patients was explored using the CIBERSORT algorithm. Subsequently, we analyzed the relationship between liver non-parenchymal cells and autophagy-related hub genes using scRNA-seq data (GSE129516). Finally, we separated the NAFLD patients into two groups based on 6 hub genes by consensus clustering and screened 10 potential autophagy-related small molecules based on the cMAP database.
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Autofagia , Redes Reguladoras de Genes , Hígado , Enfermedad del Hígado Graso no Alcohólico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Humanos , Autofagia/genética , Hígado/metabolismo , Hígado/patología , Perfilación de la Expresión Génica , Transcriptoma/genética , Biomarcadores , Biología Computacional/métodos , Bases de Datos GenéticasRESUMEN
Superstructures with complex hierarchical spatial configurations exhibit broader structural depth than single hierarchical structures and the associated broader application prospects. However, current preparation methods are greatly constrained by cumbersome steps and harsh conditions. Here, for the first time, a concise and efficient thermally responsive dynamic synthesis strategy for the preparation of multidimensional complex superstructures within soluble covalent organic networks (SCONs) with tunable morphology from 0D hollow supraparticles to 2D films is presented. Mechanism study reveals the thermally responsive dynamic "cleavage-remodeling" characteristics of SCONs, synthesized based on the unique bilayer structure of (2.2)paracyclophane, and the temperature control facilitates the process from reversible solubility to reorganization and construction of superstructures. Specifically, during the process, the oil-water-emulsion two-phase interface can be generated through droplet jetting, leading to the preparation of 0D hollow supraparticles and other bowl-like complex superstructures with high yield. Additionally, by modulating the volatility and solubility of exogenous solvents, defect-free 2D films are prepared relying on an air-liquid interface. Expanded experiments further confirm the generalizability and scalability of the proposed dynamic "cleavage-remodeling" strategy. Research on the enrichment mechanism of guest iodine highlights the superior kinetic mass transfer performance of superstructural products compared to single-hierarchical materials.
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As one of the most attractive methods for the synthesis of ordered hierarchically porous crystalline materials, the soft-template method has not appeared in covalent organic frameworks (COFs) due to the incompatibility of surfactant self-assembly and guided crystallization process of COF precursors in the organic phase. Herein, we connect the soft templates to the COF backbone through ionic bonds, avoiding their crystallization incompatibilities, thus introducing an additional ordered arrangement of soft templates into the anionic microporous COFs. The ion exchange method is used to remove the templates while maintaining the high crystallinity of COFs, resulting in the construction of COFs with ordered hierarchically micropores/mesopores, herein named OHMMCOFs (OHMMCOF-1 and OHMMCOF-2). OHMMCOFs exhibit significantly enhanced functional group accessibility and faster mass transfer rate. The extrinsic porosity can be adjusted by changing the template length, concentration, and ratio. Cationic guanidine-based COFs (OHMMCOF-3) are also constructed using the same method, which verifies the scalability of the soft-template strategy. This work provides a path for constructing ordered and tunable extrinsic porosity in COFs with greatly improved mass transfer efficiency and functional group accessibility.
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Ulcerative colitis (UC) is a complex chronic inflammatory disease closely associated with gut homeostasis dysfunction. The previous studies have shown that stachyose, a functional food additive, has the potential to enhance gut health and alleviate UC symptoms. However, the underlying mechanism of its effects remains unknown. In this study, our findings showed that dietary supplements of stachyose had a significant dose-dependent protective effect on colitis symptoms, regulation of gut microbiota, and restoration of the Treg/Th17 cell balance in dextran sulfate sodium (DSS) induced colitis mice. To further validate these findings, we conducted fecal microbiota transplantation (FMT) to treat DSS-induced colitis in mice. The results showed that microbiota from stachyose-treated mice exhibited a superior therapeutic effect against colitis and effectively regulated the Treg/Th17 cell balance in comparison to the control group. Moreover, both stachyose supplementation and FMT resulted in an increase in butyrate production and the activation of PPARγ. However, this effect was partially attenuated by PPARγ antagonist GW9662. These results suggested that stachyose alleviates UC symptoms by modulating gut microbiota and activating PPARγ. In conclusion, our work offers new insights into the benefical effects of stachyose on UC and its potential role in modulating gut microbiota.
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Butiratos , Colitis Ulcerosa , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , PPAR gamma , Transducción de Señal , Linfocitos T Reguladores , Células Th17 , Animales , PPAR gamma/metabolismo , PPAR gamma/genética , Ratones , Células Th17/inmunología , Linfocitos T Reguladores/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Masculino , Transducción de Señal/efectos de los fármacos , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/terapia , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/tratamiento farmacológico , Oligosacáridos/administración & dosificación , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Sulfato de Dextran/efectos adversosRESUMEN
Although microwave ablation (MWA) is an important curative therapy in colorectal cancer liver metastasis, recurrence still occurs clinically. Our previous studies have shown that the expression of programmed cell death 1 ligand 1 (PD-L1) is upregulated following MWA, suggesting that MWA combined with anti-PD-L1 treatment can serve as a promising clinical therapeutic strategy against cancer. Using MWA-treated preclinical mice models, MWA combined with αPD-L1 treatment decreased tumor growth and prolonged overall survival (OS). Furthermore, through flow cytometry and single-cell RNA sequencing analysis, we determined that the MWA plus αPD-L1 therapy significantly suppressed CD8+ T cell exhaustion and enhanced their effector function. A significant increase in γ-interferon (IFN-γ) stimulated transcription factors, specifically Irf8, was observed. This enhancement facilitated the polarization of tumor-associated macrophages (TAM1s and TAM2s) through the nuclear factor-κB/JAK-STAT1 signaling pathway. Furthermore, the combination therapy stimulated the production of CXC motif chemokine ligand (CXCL9) by TAM1s and tumor cells, potentially increasing the chemotaxis of CD8 T cells and Th1 cells. Knocking out Cxcl9 in MC38 tumor cells or using CXCL9 blockade enhanced tumor growth of untreated tumors and shortened OS. Taken together, our study showed that blocking the IFN-γ-Cxcl9-CD8+ T axis promoted tumor progression and discovered a potential involvement of IRF8-regulated TAMs in preventing T cell exhaustion. Collectively, we identified that the combination of MWA with anti-PD-L1 treatment holds promise as a therapeutic strategy to rejuvenate the immune response against tumors. This merits further exploration in clinical studies.
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Antígeno B7-H1 , Linfocitos T CD8-positivos , Quimiocina CXCL9 , Inhibidores de Puntos de Control Inmunológico , Microondas , Animales , Ratones , Quimiocina CXCL9/metabolismo , Quimiocina CXCL9/genética , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Microondas/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Línea Celular Tumoral , Linfocitos T CD8-positivos/inmunología , Terapia Combinada , Ratones Endogámicos C57BL , Humanos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Transducción de Señal , Femenino , Microambiente Tumoral/inmunología , Interferón gamma/metabolismo , Factor de Transcripción STAT1/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/terapiaRESUMEN
High intensity focused ultrasound (HIFU) has demonstrated its safety, efficacy and noninvasiveness in the ablation of solid tumor. However, its further application is limited by its inherent deficiencies, such as postoperative recurrence caused by incomplete ablation and excessive intensity affecting surrounding healthy tissues. Recent research has indicated that the integration of nanomaterials with HIFU exhibits a promising synergistic effect in tumor ablation. The concurrent utilization of nanomaterials with HIFU can help overcome the limitations of HIFU by improving targeting and ablation efficiency, expanding operation area, increasing operation accuracy, enhancing stability and bio-safety during the process. It also provides a platform for multi-therapy and multi-mode imaging guidance. The present review comprehensively expounds upon the synergistic mechanism between nanomaterials and HIFU, summarizes the research progress of nanomaterials as cavitation nuclei and drug carriers in combination with HIFU for tumor ablation. Furthermore, this review highlights the potential for further exploration in the development of novel nanomaterials that enhance the synergistic effect with HIFU on tumor ablation.
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Ultrasonido Enfocado de Alta Intensidad de Ablación , Nanoestructuras , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Animales , Portadores de Fármacos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Terapia CombinadaRESUMEN
The use of radiation therapy to treat pelvic and abdominal cancers can lead to the development of either acute or chronic radiation enteropathy. Radiation-induced chronic colonic fibrosis is a common gastrointestinal disorder resulting from the above radiation therapy. In this study, we establish the efficacy of inulin supplements in safeguarding against colonic fibrosis caused by irradiation therapy. Studies have demonstrated that inulin supplements enhance the proliferation of bacteria responsible to produce short-chain fatty acids (SCFAs) and elevate the levels of SCFAs in feces. In a mouse model of chronic radiation enteropathy, the transplantation of gut microbiota and its metabolites from feces of inulin-treated mice were found to reduce colonic fibrosis in validation experiments. Administering inulin-derived metabolites from gut microbiota led to a notable decrease in the expression of genes linked to fibrosis and collagen production in mouse embryonic fibroblast cell line NIH/3T3. In the cell line, inulin-derived metabolites also suppressed the expression of genes linked to the extracellular matrix synthesis pathway. The results indicate a novel and practical approach to safeguarding against chronic radiation-induced colonic fibrosis.
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Microbioma Gastrointestinal , Inulina , Animales , Ratones , Inulina/metabolismo , Fibroblastos/metabolismo , Ácidos Grasos Volátiles/metabolismo , FibrosisRESUMEN
Despite the importance of understanding how intelligence is ingrained in the function and structure of the brain in some neurological disorders, the alterations of intelligence-associated neurological factors in atypical neurodevelopmental disorders, such as attention deficit/hyperactivity disorder (ADHD), are limited. Therefore, we aimed to explore the relationship between the brain functional and morphological characteristics and the intellectual performance of 139 patients with ADHD. Resting-state functional and T1-weighted structural magnetic resonance imaging (MRI) data and intellectual-performance data of the patients were collected. The MRI data were preprocessed to extract four indicators characterizing the participants' brain features: fractional amplitude of low-frequency fluctuation, regional homogeneity, and gray and white matter volumes. Then, we used a two-layer feature-selection method with support vector regression models based on three kernel functions to predict the verbal and performance intelligent quotients of the patients, along with ten fold cross-validation to evaluate the models' predictive performance. All models showed good performance; the correlation coefficients between the predicted and observed values for each predictive phenotypic variable were >0.41, with statistical significance. The brain features that could best predict the intellectual performance of the patients were concentrated in the superior and inferior frontal gyrus of the prefrontal areas, the angular gyrus and precuneus of the parietal lobe, the inferior and middle temporal gyrus of the temporal lobe, and part of the cerebellar regions. Thus, the voxel-based brain-feature indicators could adequately predict the intellectual performance of patients with ADHD, providing a foundation for future neuroimaging studies of this disorder.
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Trastorno por Déficit de Atención con Hiperactividad , Encéfalo , Inteligencia , Imagen por Resonancia Magnética , Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Masculino , Femenino , Inteligencia/fisiología , Niño , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Adolescente , Pruebas de Inteligencia , Adulto Joven , AdultoRESUMEN
Background: Radiation resistance is the main limitation of the application of radiotherapy. Ionizing radiation (IR) kills cancer cells mainly by causing DNA damage, particularly double-strand breaks (DSBs). Radioresistant cancer cells have developed the robust capability of DNA damage repair to survive IR. Nuclear factor erythroid 2-related factor 2 (NRF2) has been correlated with radiation resistance. We previously reported a novel function of NRF2 as an ATR activator in response to DSBs. However, little is known about the mechanism that how NRF2 regulates DNA damage repair and radiation resistance. Methods: The TCGA database and tissue microarray were used to analyze the correlation between NRF2 and the prognosis of lung cancer patients. The radioresistant lung cancer cells were constructed, and the role of NRF2 in radiation resistance was explored by in vivo and in vitro experiments. Immunoprecipitation, immunofluorescence and extraction of chromatin fractions were used to explore the underlying mechanisms. Results: In this study, the TCGA database and clinical lung cancer samples showed that high expression of NRF2 was associated with poor prognosis in lung cancer patients. We established radioresistant lung cancer cells expressing NRF2 at high levels, which showed increased antioxidant and DNA repair abilities. In addition, we found that NRF2 can be involved in the DNA damage response independently of its antioxidant function. Mechanistically, we demonstrated that NRF2 promoted the phosphorylation of replication protein A 32 (RPA32), and DNA topoisomerase 2-binding protein 1 (TOPBP1) was recruited to DSB sites in an NRF2-dependent manner. Conclusion: This study explored the novel role of NRF2 in promoting radiation resistance by cooperating with RPA32 and TOPBP1 to activate the ATR-CHK1 signaling pathway. In addition, the findings of this study not only provide novel insights into the molecular mechanisms underlying the radiation resistance of lung cancer cells but also validate NRF2 as a potential target for radiotherapy.
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Proteínas Portadoras , Neoplasias Pulmonares , Humanos , Antioxidantes/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular/metabolismo , Daño del ADN , Proteínas de Unión al ADN/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Fosforilación , Transducción de SeñalRESUMEN
A high level of reduced glutathione is a major factor contributing to the radioresistance observed in solid tumors. To address this radioresistance associated with glutathione, a cinnamaldehyde (CA) polymer prodrug, referred to as PDPCA, is fabricated. This prodrug is created by synthesizing a pendent CA prodrug with acetal linkages in a hydrophobic block, forming a self-assembled into a core-shell nanoparticle in aqueous media. Additionally, it encapsulates all-trans retinoic acid (ATRA) for synchronous delivery, resulting in PDPCA@ATRA. The PDPCA@ATRA nanoparticles accumulate reactive oxygen species through both endogenous and exogenous pathways, enhancing ferroptosis by depleting glutathione. This approach demonstrates efficacy in overcoming tumor radioresistance in vivo and in vitro, promoting the ferroptosis, and enhancing the cytotoxic T lymphocyte (CTL) response for lung tumors to anti-PD-1 (αPD-1) immunotherapy. Furthermore, this study reveals that PDPCA@ATRA nanoparticles promote ferroptosis through the NRF2-GPX4 signaling pathway, suggesting the potential for further investigation into the combination of radiotherapy and αPD-1 immune checkpoint inhibitors in cancer treatment.
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Acroleína/análogos & derivados , Ferroptosis , Neoplasias Pulmonares , Profármacos , Humanos , Nanomedicina , Inmunoterapia , Glutatión , Profármacos/farmacología , Especies Reactivas de Oxígeno , Línea Celular TumoralRESUMEN
BACKGROUND: Alveolar epithelial injury and dysfunction are the risk factors for radiation-induced pulmonary fibrosis (RIPF). However, it is not clear about the relationship between RIPF and the small extracellular vesicles (sEV) secreted by irradiated alveolar epithelial cells. Based on the activation of fibroblasts, this study explored the role of sEV derived from alveolar epithelial cells in RIPF and the potential mechanisms. METHODS: Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were used to characterize sEV. Western blotting was used to detect fibrosis-associated proteins. Cell counts and transwell assays were used to evaluate the proliferation and migration ability of fibroblasts. RT-PCR was used to observe the extracellular matrix (ECM) synthesized by fibroblasts, miRNA changes in the sEV were determined by second-generation sequencing. RESULTS: TEM, NTA, and western blotting showed the extracellular vesicles with a double-layer membrane structure of approximately 100 nm in diameter. The sEV derived from irradiated A549, HBEC3-KT, and MLE12 cells upregulated FN1 and alpha-SMA proteins expression in fibroblasts and drove the fibroblast to myofibroblast transition, and the sEV from irradiated mouse bronchoalveolar lavage fluid (BALF) affirmed the same results. In addition, the sEV derived from irradiated alveolar epithelial cells significantly increased the migration ability of fibroblasts and the expression of extracellular matrix proteins such as FN1. The results of miRNA sequencing of sEV in BALF of rats with RIPF showed that the metabolic pathway may be important for miRNA to regulate the activation of fibroblasts. CONCLUSION: The sEV derived from radiated pulmonary epithelial cells promote the activation, migration and extracellular matrix proteins expression of lung fibroblasts; miRNA in sEV may be an important molecular that affects the activation of lung fibroblasts.
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Vesículas Extracelulares , MicroARNs , Fibrosis Pulmonar , Ratas , Ratones , Animales , Fibrosis Pulmonar/etiología , Pulmón/metabolismo , Células Epiteliales/patología , MicroARNs/genética , MicroARNs/metabolismo , Fibroblastos/metabolismo , Vesículas Extracelulares/metabolismo , Proteínas de la Matriz Extracelular/efectos adversos , Proteínas de la Matriz Extracelular/metabolismoRESUMEN
Thermal ablation results in the damage of tumor tissue, which leads to localized necrosis and incites a significant inflammatory response, accompanied by the infiltration of numerous immune cells. Nevertheless, depending solely on the singular approach of thermal ablation frequently is difficult in eliciting a robust anti-tumor response. Research suggests that integrating immune modulators into conventional ablation techniques has the potential to enhance the elicited immune response, finally initiating synergistic effect without significantly elevated risk profiles. This article comprehensively analyses the immunological effects resulting from post-ablation alone and its synergy with immunotherapies, and accentuates the heterogeneous alterations noted in immune cells across distinct malignancies. Collectively, the article delves into the theoretical framework and advancements in clinical trials concerning the combined thermal ablation and immunotherapy for treating malignant tumors.
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BACKGROUND: The dose-response relationship between cancers and protracted low-dose rate exposure to ionising radiation is still uncertain. This study aims to estimate quantified relationships between low-dose radiation exposures and site-specific solid cancers among Chinese medical X-ray workers. METHODS: This cohort study included 27 011 individuals who were employed at major hospitals in 24 provinces in China from 1950 to 1980 and had been exposed to X-ray equipment, and a control group of 25 782 physicians who were not exposed to X-ray equipment. Person-years of follow-up were calculated from the year of employment to the date of the first diagnosis of cancer or the end of follow-up, whichever occurred first. All cancers were obtained from medical records during 1950-1995. This study used Poisson regression models to estimate the excess relative risk (ERR) and excess absolute risk (EAR) for incidence of site-specific solid cancers associated with cumulative dose. RESULTS: 1643 solid cancers were developed, the most common being lung, liver and stomach cancer. Among X-ray workers, the average cumulative colon dose was 0.084 Gy. We found a positive relationship between cumulative organ-specific dose and liver (ERR/Gy=1.48; 95% CI 0.40 to 2.83), oesophagus (ERR/Gy=18.1; 95% CI 6.25 to 39.1), thyroid (ERR/Gy=2.96; 95% CI 0.44 to 8.18) and non-melanoma skin cancers (ERR/Gy=7.96; 95% CI 2.13 to 23.12). We found no significant relationship between cumulative organ-specific doses and other cancers. Moreover, the results showed a statistically significant EAR for liver, stomach, breast cancer (female), thyroid and non-melanoma skin cancers. CONCLUSIONS: These findings provided more useful insights into the risks of site-specific cancers from protracted low-dose rate exposure to ionising radiation.
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Personal de Salud , Neoplasias Inducidas por Radiación , Exposición Profesional , Radiación Ionizante , Femenino , Humanos , Neoplasias de la Mama , Estudios de Cohortes , Pueblos del Este de Asia , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/etiología , Exposición Profesional/efectos adversos , Dosis de Radiación , Neoplasias Cutáneas , Rayos X/efectos adversosRESUMEN
Ionizing radiation (IR) causes a wide variety of DNA lesions, of which DNA double-stranded breaks (DSBs) are the most deleterious. Homologous recombination (HR) is a crucial route responsible for repairing DSBs. RecQ-mediated genome instability protein 1 (RMI1) is a member of an evolutionarily conserved Bloom syndrome complex, which prevents and resolves aberrant recombination products during HR, thereby promoting genome stability. However, little is known about the role of RMI1 in regulating the cellular response to IR. This study aimed to understand the cellular functions and molecular mechanisms by which RMI1 maintains genomic stability after IR exposure. Here, we showed IR upregulated the RMI1 protein level and induced RMI1 relocation to the DNA damage sites. We also demonstrated that the loss of RMI1 in cells resulted in enhanced levels of DNA damage, sustained cell cycle arrest, and impaired HR repair after IR, leading to reduced cell viability and elevated genome instability. Taken together, our results highlighted the direct roles of RMI1 in response to DNA damage induced by IR and implied that RMI1 might be a new genome safeguard molecule to radiation-induced damage.
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Sonodynamic therapy (SDT) is a new non-invasive treatment method proposed based on photodynamic therapy (PDT). It has advantages such as high precision, strong tissue penetration, minimal side effects, and good patient compliance. With the maturation of nanomedicine, the application of nanosonosensitizers has further propelled the development of SDT. In recent years, people have developed many new types of sonosensitizers and explored the mechanisms of SDT. Among them, the studies about the relationship between autophagy and SDT have attracted increasing attention. After the SDT, cells usually undergo autophagy as a self-protective mechanism to resist external stimuli and reduce cell damage, which is beneficial for the treatment of atherosclerosis (AS), diabetes, and myocardial infarction but counterproductive in cancer treatment. However, under certain treatment conditions, excessive upregulation of autophagy can also promote cell death, which is beneficial for cancer treatment. This article reviews the latest research progress on the relationship between SDT and autophagy in cancers, AS, diabetes, and myocardial infarction. We also discuss and propose the challenges and prospects in enhancing SDT efficacy by regulating autophagy, with the hope of promoting the development of this promising therapeutic approach.
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Aterosclerosis , Diabetes Mellitus , Infarto del Miocardio , Terapia por Ultrasonido , Humanos , Especies Reactivas de Oxígeno/metabolismo , Terapia por Ultrasonido/métodos , Autofagia , Infarto del Miocardio/terapiaRESUMEN
Accumulating evidence has shown that gut microbiota and its metabolites have important significance in the etiology of obesity and related disorders. Prebiotics prevent and alleviate obesity by modulating the gut microbiota. However, how pectin oligosaccharides (POS) derived from pectin degradation affect gut microbiota and obesity remains unclear. To investigate the potential anti-obesity effects of POS, mice were fed a high-fat diet (HFD) for 12 weeks and a POS supplement with drinking water during the last 8 weeks. The outcomes demonstrated that POS supplementation in HFD-fed mice decreased body weight (P < 0.01), improved glucose tolerance (P < 0.001), reduced fat accumulation (P < 0.0001) and hepatic steatosis, protected intestinal barrier, and reduced pro-inflammatory cytokine levels. After fecal metagenomic sequencing, the POS corrected the gut microbiota dysbiosis caused by the HFD, as shown by the increased populations of Bifidobacterium, Lactobacillus taiwanensis, and Bifidobacterium animalis, and decreased populations of Alistipes and Erysipelatoclostridium, which were previously considered harmful bacteria. Notably, the changed gut microbiota was associated with the obesity prevention of POS. These findings demonstrate that POS regulates particular gut microbiota, which is essential owing to its ability to prevent disorders associated with obesity.