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Disulfidoptosis and ferroptosis are two distinct programmed cell death pathways that have garnered considerable attention due to their potential as therapeutic targets. However, despite their significance of these pathways, the role of disulfidoptosis-related ferroptosis genes in hepatocellular carcinoma (HCC) remains unclear. In this study, we employed a comprehensive approach that utilized various sophisticated techniques such as Pearson analysis, differential analysis, uniCox regression, lasso, ranger, and multivariable Cox regression to develop the disulfidoptosis-related ferroptosis (DRF) score. We then classified patients with HCC into high- and low-score groups to examine the association between the DRF score and various outcomes, including prognosis, functional enrichment, immune infiltration, immunotherapy, TACE sensitivity, drug sensitivity, and single-cell level function. Finally, we conducted in vitro experiments to validate the function of KIF20A. Our analysis revealed that KIF20A, G6PD, SLC7A11, and SLC2A1 were integral to constructing the DRF score. Our findings showed that patients with low DRF scores had significantly better prognoses and were more responsive to immunotherapy, TACE, and chemotherapy than those with high DRF scores. Based on our results obtained from bulk RNA-seq, single-cell RNA-seq, and in vitro experiments, we identified the cell cycle pathway as the primary distinguished factor between high-score and low-score groups. This study sheds light on the contribution of disulfidoptosis-related ferroptosis genes to the development and progression of HCC. The information gleaned from this study can be leveraged to improve our understanding of their potential as therapeutic targets for HCC treatment.
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Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Humanos , Apoptosis , Carcinoma Hepatocelular/genética , Ferroptosis/genética , Neoplasias Hepáticas/genética , Aprendizaje AutomáticoRESUMEN
The global burden of hepatocellular carcinoma (HCC) as a preeminent etiology of cancer-related mortalities sheds light on the imperative necessity for a more profound comprehension of its fundamental biological mechanisms. In this context, the precise function of the 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) in HCC remains equivocal. To address this vital knowledge gap, we interrogated the cancer genome atlas, genotype-tissue expression, International cancer genome consortium, gene expression omnibus, the cancer cell line encyclopedia, and tumor immune single-cell hub databases to evaluate the expression pattern of PSMD11, further confirmed by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) in LO2, MHCC-97H, HepG2, and SMMC7721 cell lines. Additionally, we meticulously assessed the clinical significance and prognostic value of PSMD11, while also exploring its potential molecular mechanisms in HCC. Our findings demonstrated that PSMD11 was highly expressed in HCC tissues, correlating with pathologic stage and histologic grade, thereby conferring a poor prognosis. Mechanistically, PSMD11 appears to exert its tumorigenic effects through the modulation of tumor metabolism-related pathways. Impressively, low PSMD11 expression was associated with increased immune effector cell infiltration, heightened responsiveness to molecular targeted drugs such as dasatinib, erlotinib, gefitinib, and imatinib, as well as reduced somatic mutation rate. Additionally, we demonstrated that PSMD11 might modulate HCC development through intricate interactions with cuproptosis-related genes ATP7A, DLAT, and PDHA1. Our comprehensive analyses collectively suggest that PSMD11 represents a promising therapeutic target in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Pronóstico , Complejo de la Endopetidasa ProteasomalRESUMEN
This study aims to explore the link between retinal vein occlusion (RVO), a blinding ocular condition, and alterations in gut microbiota composition, to offer insights into the pathogenesis of RVO. Fecal samples from 25 RVO patients and 11 non-RVO individuals were analyzed using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS). Significant differences in the abundance of gut microbial species were noted between RVO and non-RVO groups. At the phylum level, the RVO group showed an elevation in the ratio of Firmicutes to Bacteroidetes. At the genus level, the RVO group showed higher abundance in Escherichia_Shigella (P < 0.05) and less abundance in Parabacteroides (P < 0.01) than the non-RVO group. Functional predictions indicated reduced folate synthesis, biotin metabolism, and oxidative phosphorylation, with an increase in butyric acid metabolism in the RVO group. LC-MS analysis showed significant differences in purine metabolism, ABC transporters, and naphthalene degradation pathways, especially purine metabolism. Pearson correlation analysis revealed significant associations between bacterial genera and fecal metabolites. Enrichment analysis highlighted connections between specific metabolites and bacterial genera. The findings showed that the dysregulation of gut microbiota was observed in RVO patients, suggesting the gut microbiota as a potential therapeutic target. Modulating the gut microbiota could be a novel strategy for managing RVO and improving patient outcomes. Furthermore, the study findings suggest the involvement of gut microbial dysbiosis in RVO development, underscoring the significance of understanding its pathogenesis for effective treatment development. IMPORTANCE: Retinal vein occlusion (RVO) is a blinding ocular condition, and understanding its pathogenesis is crucial for developing effective treatments. This study demonstrates significant differences in gut microbiota composition between RVO patients and non-RVO individuals, implicating the involvement of gut microbial dysbiosis in RVO development. Functional predictions and metabolic profiling provide insights into the underlying mechanisms, highlighting potential pathways for therapeutic intervention. These findings suggest that modulating the gut microbiota might be a promising strategy for managing RVO and improving patient outcomes.
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Bacterias , Heces , Microbioma Gastrointestinal , Metabolómica , ARN Ribosómico 16S , Oclusión de la Vena Retiniana , Humanos , Oclusión de la Vena Retiniana/metabolismo , Oclusión de la Vena Retiniana/microbiología , Heces/microbiología , Masculino , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética , Bacterias/aislamiento & purificación , Persona de Mediana Edad , Femenino , ARN Ribosómico 16S/genética , Anciano , Adulto , Cromatografía LiquidaRESUMEN
RATIONALE AND OBJECTIVES: This study aimed to propose a novel approach of lipiodol combined with drug-eluting beads transarterial chemoembolization (Lipiodol-DEB TACE) and to compare the safety and efficacy with DEB-TACE alone for patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From the database of four centers, the records of patients with HCC who received DEB-TACE or Lipiodol-DEB TACE as initial treatment were retrospectively evaluated. The tumor response was measured based on the Modified Response Evaluation Criteria in Solid Tumors. Overall survival (OS), progression-free survival (PFS) and adverse events (AEs) were compared between two groups. RESULTS: A total of 244 patients were included with 160 patients receiving DEB-TACE and 84 patients receiving Lipiodol-DEB TACE. Lipiodol-DEB TACE group had higher objective response rate (86.9 % vs. 76.3 %), higher disease control rate (97.6 % vs. 88.8 %), longer median OS (42.6 vs. 25.8 months) and longer median PFS (34.0 vs. 17.0 months) than DEB-TACE group (P < 0.05). There was no significant difference observed in the incidence of AEs between two groups. Cox analysis identified total bilirubin level, maximum tumor diameter, TACE method and portal vein invasion as independent prognostic factors. CONCLUSION: Lipiodol-DEB TACE was a safe option and associated with improved tumor response and survival outcome compared to DEB-TACE alone for selected patients with HCC.
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OBJECTIVE: To provide suggestion for MDAEs monitoring with analyzing the features of the 1028 reports of MDAEs. METHODS: With retrospective case study, this paper analyzed 1 028 MDAE reports in Guiyang during 2012. RESULTS: The intrauterine device (IUD) caused the higher proportion of adverse events with serious degree. Monitoring consciousness of grassroots users needs to be improved. The quality of the reports should be enhanced. CONCLUSIONS: More attention should be paid to monitoring on IUD. The level of MDAEs monitoring should be improved through carrying out targeted training and publicity, establishing and improving MDAEs monitoring network.
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Dispositivos Intrauterinos/efectos adversos , Vigilancia de Productos Comercializados , Seguridad de Equipos , Estudios RetrospectivosRESUMEN
The conversion of CO2 into clean fuels by utilizing solar energy is still limited by a low photoconversion efficiency, and heterojunction photocatalysts are considered a very effective way to solve this problem. Herein, a heterojunction system consisting of hematite (α-Fe2O3) and boron carbonitride (BCN) was fabricated through a one-pot ionothermal method. α-Fe2O3 nanoparticles were grown in situ on the surface of BCN nanosheets, forming an α-Fe2O3/BCN heterojunction (FBCN) with tiny amounts of α-Fe2O3 (less than 2 wt%). The as-synthesized FBCN catalyst with 1.46 wt% α-Fe2O3 provides the highest CO2 photoreduction activity (55.1 µmol g-1 for CO) without any cocatalyst or sacrificial reagents, which is 3.9 times higher than that obtained for pure BCN. The enhanced CO2 reduction activity can be attributed to the high surface area and effective interface-contacted heterostructure, which endows the catalyst with broadband visible light absorption, suppressed separation of photogenerated electron holes, and promoted charge transfer. Meanwhile, cycling experiments demonstrate that the FBCN photocatalyst shows good reusability and stability. This work can assist in the design and preparation of BCN-based heterojunctions with effective CO2 reduction performance.
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Loading a noble metal on Bi4Ti3O12 could enable the formation of the Schottky barrier at the interface between the former and the latter, which causes electrons to be trapped and inhibits the recombination of photoelectrons and photoholes. In this paper, AgPt/Bi4Ti3O12 composite photocatalysts were prepared using the photoreduction method, and the effects of the type and content of noble metal on the photocatalytic performance of the catalysts were investigated. The photocatalytic degradation of rhodamine B (RhB) showed that the loading of AgPt bimetallic nanoparticles significantly improved the catalytic performance of Bi4Ti3O12. When 0.10 wt% noble metal was loaded, the degradation rate for RhB of Ag0.7Pt0.3/Bi4Ti3O12 was 0.027 min-1, which was respectively about 2, 1.7 and 3.7 times as that of Ag/Bi4Ti3O12, Pt/Bi3Ti4O12 and Bi4Ti3O12. The reasons may be attributed as follows: (i) the utilization of visible light was enhanced due to the surface plasmon resonance effect of Ag and Pt in the visible region; (ii) Ag nanoparticles mainly acted as electron acceptors to restrain the recombination of photogenerated electron-hole pairs under visible light irradiation; and (iii) Pt nanoparticles acted as electron cocatalysts to further suppress the recombination of photogenerated electron-hole pairs. The photocatalytic performance of Ag0.7Pt0.3/Bi4Ti3O12 was superior to that of Ag/Bi4Ti3O12 and Pt/Bi3Ti4O12 owing to the synergistic effect between Ag and Pt nanoparticles.