ABSTRACT
The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LDs) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. For example, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and the proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Our analyses showed reductions in LD volume, area, and perimeter in aged samples in comparison to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for the mitochondria interacting with LDs. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology with mitochondrial function, metabolism, and bioactivity in aged BAT.
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The liver, the largest internal organ and a metabolic hub, undergoes significant declines due to aging, affecting mitochondrial function and increasing the risk of systemic liver diseases. How the mitochondrial three-dimensional (3D) structure changes in the liver across aging, and the biological mechanisms regulating such changes confers remain unclear. In this study, we employed Serial Block Face-Scanning Electron Microscopy (SBF-SEM) to achieve high-resolution 3D reconstructions of murine liver mitochondria to observe diverse phenotypes and structural alterations that occur with age, marked by a reduction in size and complexity. We also show concomitant metabolomic and lipidomic changes in aged samples. Aged human samples reflected altered disease risk. To find potential regulators of this change, we examined the Mitochondrial Contact Site and Cristae Organizing System (MICOS) complex, which plays a crucial role in maintaining mitochondrial architecture. We observe that the MICOS complex is lost during aging, but not Sam50. Sam50 is a component of the sorting and assembly machinery (SAM) complex that acts in tandem with the MICOS complex to modulate cristae morphology. In murine models subjected to a high-fat diet, there is a marked depletion of the mitochondrial protein SAM50. This reduction in Sam50 expression may heighten the susceptibility to liver disease, as our human biobank studies corroborate that Sam50 plays a genetically regulated role in the predisposition to multiple liver diseases. We further show that changes in mitochondrial calcium dysregulation and oxidative stress accompany the disruption of the MICOS complex. Together, we establish that a decrease in mitochondrial complexity and dysregulated metabolism occur with murine liver aging. While these changes are partially be regulated by age-related loss of the MICOS complex, the confluence of a murine high-fat diet can also cause loss of Sam50, which contributes to liver diseases. In summary, our study reveals potential regulators that affect age-related changes in mitochondrial structure and metabolism, which can be targeted in future therapeutic techniques.
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The kidney filters nutrient waste and bodily fluids from the bloodstream, in addition to secondary functions of metabolism and hormone secretion, requiring an astonishing amount of energy to maintain its functions. In kidney cells, mitochondria produce adenosine triphosphate (ATP) and help maintain kidney function. Due to aging, the efficiency of kidney functions begins to decrease. Dysfunction in mitochondria and cristae, the inner folds of mitochondria, is a hallmark of aging. Therefore, age-related kidney function decline could be due to changes in mitochondrial ultrastructure, increased reactive oxygen species (ROS), and subsequent alterations in metabolism and lipid composition. We sought to understand if there is altered mitochondrial ultrastructure, as marked by 3D morphological changes, across time in tubular kidney cells. Serial block facing-scanning electron microscope (SBF-SEM) and manual segmentation using the Amira software were used to visualize murine kidney samples during the aging process at 3 months (young) and 2 years (old). We found that 2-year mitochondria are more fragmented, compared to the 3-month, with many uniquely shaped mitochondria observed across aging, concomitant with shifts in ROS, metabolomics, and lipid homeostasis. Furthermore, we show that the mitochondrial contact site and cristae organizing system (MICOS) complex is impaired in the kidney due to aging. Disruption of the MICOS complex shows altered mitochondrial calcium uptake and calcium retention capacity, as well as generation of oxidative stress. We found significant, detrimental structural changes to aged kidney tubule mitochondria suggesting a potential mechanism underlying why kidney diseases occur more readily with age. We hypothesize that disruption in the MICOS complex further exacerbates mitochondrial dysfunction, creating a vicious cycle of mitochondrial degradation and oxidative stress, thus impacting kidney health.
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Nonsmall cell lung cancer (NSCLC) is one of the major causes of cancerrelated death worldwide. Cisplatin is a frontline chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatinmediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcriptionquantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROSmediated endoplasmic reticulum stress, and the CJunaminoterminal kinase and p38 mitogenactivated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROSmediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Cisplatin , Drug Synergism , Glucosides , Lung Neoplasms , NADPH Oxidase 5 , Oxidative Stress , Reactive Oxygen Species , Stilbenes , Xenograft Model Antitumor Assays , Cisplatin/pharmacology , Cisplatin/therapeutic use , Glucosides/pharmacology , Glucosides/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Animals , Humans , Stilbenes/pharmacology , Stilbenes/therapeutic use , Mice , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Apoptosis/drug effects , A549 Cells , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Proliferation/drug effects , Endoplasmic Reticulum Stress/drug effects , Gene Expression Regulation, Neoplastic/drug effects , MaleABSTRACT
The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LD) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. Particularly, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Analysis showed reductions in LD volume, area, and perimeter in aged samples compared to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for mitochondria interacting with LD lipids. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology and mitochondrial functionality, metabolism, and bioactivity in aged BAT.
ABSTRACT
The sorting and assembly machinery (SAM) Complex is responsible for assembling ß-barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block-face-scanning electron microscopy and computer-assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50-deficient myotubes from mice and humans with wild-type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography-Mass Spectrometry-based metabolomics to explore differential changes in WT and Sam50-deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50-deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß-Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50-deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50-deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle.
Subject(s)
Muscle Fibers, Skeletal , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/ultrastructure , Animals , Humans , Mice , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Mitochondria/metabolism , Mitochondria/ultrastructure , Mitochondrial Membranes/metabolism , Mitochondria, Muscle/metabolism , Mitochondria, Muscle/ultrastructure , Mice, Knockout , Autophagy , Mitochondrial Precursor Protein Import Complex ProteinsABSTRACT
OBJECTIVE: To assess the ability of markers of inflammation to identify the solid or micropapillary components of stage IA lung adenocarcinoma and their effects on prognosis. METHODS: We performed a retrospective study of clinicopathologic data from 654 patients with stage IA lung adenocarcinoma collected between 2013 and 2019. Logistic regression analysis was used to identify independent predictors of these components, and we also evaluated the relationship between markers of inflammation and recurrence. RESULTS: Micropapillary-positive participants had high preoperative neutrophil-to-lymphocyte ratios. There were no significant differences in the levels of markers of systemic inflammation between the participants with or without a solid component. Multivariate analysis showed that preoperative neutrophil-to-lymphocyte ratio (odds ratio [OR] = 2.094; 95% confidence interval [CI], 1.668-2.628), tumor size (OR = 1.386; 95% CI, 1.044-1.842), and carcinoembryonic antigen concentration (OR = 1.067; 95% CI, 1.017-1.119) were independent predictors of a micropapillary component. There were no significant correlations between markers of systemic inflammation and the recurrence of stage IA lung adenocarcinoma. CONCLUSIONS: Preoperative neutrophil-to-lymphocyte ratio independently predicts a micropapillary component of stage IA lung adenocarcinoma. Therefore, the potential use of preoperative neutrophil-to-lymphocyte ratio in the optimization of surgical strategies for the treatment of stage IA lung adenocarcinoma should be further studied.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Lymphocytes , Neoplasm Staging , Neutrophils , Humans , Neutrophils/pathology , Male , Female , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/blood , Adenocarcinoma of Lung/diagnosis , Middle Aged , Lung Neoplasms/surgery , Lung Neoplasms/blood , Lung Neoplasms/pathology , Lung Neoplasms/diagnosis , Aged , Lymphocytes/pathology , Retrospective Studies , Prognosis , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/blood , Lymphocyte Count , Biomarkers, Tumor/blood , Preoperative Period , AdultABSTRACT
The development of large-scale, high-quality ferroelectric semiconductor nanowire arrays with interesting light-emitting properties can address limitations in traditional wide-bandgap ferroelectrics, thus serving as building blocks for innovative device architectures and next-generation high-density optoelectronics. Here, we investigate the optical properties of ferroelectric CsGeX3 (X = Br, I) halide perovskite nanowires that are epitaxially grown on muscovite mica substrates by vapor phase deposition. Detailed structural characterizations reveal an incommensurate heteroepitaxial relationship with the mica substrate. Furthermore, photoluminescence that can be tuned from yellow-green to red emissions by varying the halide composition demonstrates that these nanowire networks can serve as platforms for future optoelectronic applications. In addition, the room-temperature ferroelectricity and ferroelectric domain structures of these nanowires are characterized using second harmonic generation (SHG) polarimetry. The combination of room-temperature ferroelectricity with photoluminescence in these nanowire arrays unlocks new avenues for the design of novel multifunctional materials.
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Age-related atrophy of skeletal muscle, is characterized by loss of mass, strength, endurance, and oxidative capacity during aging. Notably, bioenergetics and protein turnover studies have shown that mitochondria mediate this decline in function. Although exercise has been the only therapy to mitigate sarcopenia, the mechanisms that govern how exercise serves to promote healthy muscle aging are unclear. Mitochondrial aging is associated with decreased mitochondrial capacity, so we sought to investigate how aging affects mitochondrial structure and potential age-related regulators. Specifically, the three-dimensional (3D) mitochondrial structure associated with morphological changes in skeletal muscle during aging requires further elucidation. We hypothesized that aging causes structural remodeling of mitochondrial 3D architecture representative of dysfunction, and this effect is mitigated by exercise. We used serial block-face scanning electron microscopy to image human skeletal tissue samples, followed by manual contour tracing using Amira software for 3D reconstruction and subsequent analysis of mitochondria. We then applied a rigorous in vitro and in vivo exercise regimen during aging. Across 5 human cohorts, we correlate differences in magnetic resonance imaging, mitochondria 3D structure, exercise parameters, and plasma immune markers between young (under 50 years) and old (over 50 years) individuals. We found that mitochondria we less spherical and more complex, indicating age-related declines in contact site capacity. Additionally, aged samples showed a larger volume phenotype in both female and male humans, indicating potential mitochondrial swelling. Concomitantly, muscle area, exercise capacity, and mitochondrial dynamic proteins showed age-related losses. Exercise stimulation restored mitofusin 2 (MFN2), one such of these mitochondrial dynamic proteins, which we show is required for the integrity of mitochondrial structure. Furthermore, we show that this pathway is evolutionarily conserved as Marf, the MFN2 ortholog in Drosophila, knockdown alters mitochondrial morphology and leads to the downregulation of genes regulating mitochondrial processes. Our results define age-related structural changes in mitochondria and further suggest that exercise may mitigate age-related structural decline through modulation of mitofusin 2.
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The metal-halide ionic octahedron is the optoelectronic unit for halide perovskites, and a crown ether-assisted supramolecular assembly approach can pack various ionic octahedra into tunable symmetries. In this work, we demonstrate near-unity photoluminescence quantum yield (PLQY) blue and green emission with the supramolecular assembly of hafnium (Hf) and zirconium (Zr) halide octahedral clusters. (18C6@K)2HfBr6 powders showed blue emission with a near-unity PLQY (96.2%), and green emission was also achieved with (18C6@K)2ZrCl4Br2 powders at a PLQY of 82.7%. These highly emissive powders feature facile low-temperature solution-based synthesis conditions and maintain high PLQY in solution-processable semiconductor inks under ambient conditions, and they were used in thin-film displays and emissive three-dimensional-printed architectures that exhibited high spatial resolution.
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Background Job burnout has become an important factor affecting the mental and physical health and work efficiency of college counselors, and indirectly affects the quality and development of talent cultivation for college students. Objective To explore the relationship between job stress, job crafting, and job burnout among college counselors, and to test the mediating role of job crafting between job stress and job burnout, in order to take targeted measures to alleviate job stress and job burnout of college counselors, reduce associated health risks, and improve the effectiveness of higher education. Methods An anonymous questionnaire survey was conducted among 400 counselors from social network communication groups by convenience sampling. The Counselor Work Stress Scale, Job Crafting Scale, and Maslach Burnout Inventory-General Survey were used. Harman's single-factor method was used to evaluate common method bias in the survey data. One-way ANOVA was applied to test the difference in job stress, job crafting, and job burnout among college counselors by demographic characteristics, and chi-square test was used to analyze the difference in reporting job burnout. Partial correlation analysis was used to evaluate the correlation between selected variables. Structural equation modeling was used to analyze the relationship of job stress, job crafting, and job burnout among college counselors, and Bootstrap analysis was used to test if there was a mediating effect of job crafting on the relationship between job stress and job burnout. Results Of the 390 questionnaires recovered, there were 338 valid questionnaires (86.67%). Among the included subjects, the mean scores of job stress, job crafting, and job burnout were (2.70±0.62), (3.77±0.62), and (2.09±1.09), respectively. The positive rate of job burnout was 76.9% (260/338), with a positive rate of 72.8% in exhaustion dimension and 59.8% in cynicism dimension. There were significant differences in job crafting scores among the college counselors by different genders and professional titles (P<0.05). Female counselors had significantly higher job burnout scores and positive rates than male counselors (P<0.05). The partial correlation analysis showed that job stress, work load, school evaluation and expectation, and interpersonal relationship were positively correlated with job burnout (r=0.562, 0.442, 0.473, and 0.455, respectively, P<0.01), and negatively correlated with job crafting (r=−0.271, −0.169, −0.246, and −0.247, respectively, P<0.01); job crafting, cognitive crafting, relationship crafting, and task crafting were negatively correlated with job burnout (r=−0.447, −0.452, −0.366, and −0.340, respectively, P<0.01). The modified structural equation modeling indicated that job stress negatively affected job crafting (b=−0.348, P<0.001) and positively affected job burnout (b=0.454, P<0.001); job crafting negatively affected job burnout (b=−0.459, P<0.001), and played a partial mediating role in the relationship between job stress and job burnout, and the effect value was 0.160 (95%CI: 0.102, 0.230) that accounted for 26.10% of the total effect. Conclusion Job burnout among the college counselors is prominent. Job crafting presents an inhibitory effect on job burnout. Job stress indirectly affects the occurrence of job burnout by inhibiting the generation of job crafting.
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Aging is a process of degenerative change that occurs as a result of time-related accumulation,associated with age-related diseases.Understanding the causes and mechanisms of aging and finding drugs that can effectively delay aging and prevent and cure age-related diseases currently present a great challenge for humans.Aging animal models thus represent an important tool in aging research,and various aging animal models have been created using different aging mechanisms.These different models having specific advantages and disadvantages,making them suitable for different research purposes.This review considers aging rodent models to provide information for aging research.
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Purpose@#To study the long-term efficacy and safety of Flexivue Microlens refractive corneal inlays in Koreans for compensation of presbyopia. @*Methods@#Flexivue Microlens inlays were implanted in nine eyes at Samsung Medical Center from October 2015 to February 2018. The follow-up period was 1.95 ± 0.6 years. Pre- and postoperative near/intermediate/distant visual acuity, spherical equivalent, contrast sensitivity, defocus curve, keratometry, and patient satisfaction were evaluated retrospectively. @*Results@#The uncorrected near visual acuity (UNVA) of the operated eye increased significantly to 0.27 ± 0.10 logarithm of the minimal angle resolution (logMAR) after 6 months (p = 0.012). At the last observation, it was 0.32 ± 0.21 logMAR, which improved compared to before surgery, but the difference was not significant (p = 0.127). The binocular UNVA improved significantly to 0.19 ± 0.78 logMAR at 6 months postoperatively (p = 0.017) and to 0.21 ± 0.13 logMAR at the last observation (p = 0.028). There was no difference in the binocular uncorrected distant visual acuity (UDVA) before and after surgery, but the UDVA of the operated eye decreased significantly to 0.38 ± 0.15 logMAR at 6 months postoperatively (p = 0.007) and to 0.32 ± 0.21 logMAR at the last observation (p = 0.012). Satisfaction with near vision improved significantly after surgery; 14.3% of the patients had a score of 4 (good) or higher and 42.9% did not require near-vision glasses. In one case, the inlay was removed after 17 months due to blurred vision. @*Conclusions@#The Flexivue Microlens has a low risk of complications and is a reversible technique. However, the near vision improvement was temporary and distance vision deteriorated. In addition, the Koreans examined had relatively low satisfaction and high spectacle dependence.
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Multiple organs are physiologically and pathologically interconnected during aging, and the brain plays a central role in this process. There is a direct two-way communication between the brain and the gut called “brain-gut interaction”, which is of great significance for the study of aging, and the molecular mechanism remains to be further studied. The aim of this study is to explore the mechanism of aging in the context of brain-gut interaction. The results of general physical signs of mice showed that the amount of exercise decreased, body weight and food intake decreased significantly in aged mice (P < 0. 001, P<0. 05). The thymus index of aged mice was significantly lower than that of normal mice (P< 0. 05), and the thymic pathological results showed that the thymic cortex of aging mice was thinner, the boundary between medulla and cortex was blurred, and the cells were loosely arranged. Metabolomics analysis revealed 317 differential metabolites in feces and 100 differential metabolites in hippocampus. The results of microbiome showed that Bacteroidetes and Firmicutes were the dominant phyla of gut microbiota. Bacteroidetes showed an upward trend and Firmicutes showed a downward trend after aging. KEGG pathway results showed that 26 metabolic pathways were related to the study of aging, among which galactose metabolism, ABC transporter and purine metabolism were of great significance for the brain-gut interaction. The results of Spearman correlation analysis of the three groups showed that the types of metabolites involved were mainly lipids and lipid-like molecules and organic acids and derivatives, and the gut microbiota involved were mainly Bacteroidetes and Firmicutes. In conclusion, the present study demonstrated that the synergistic changes between brain and gut in aging mice were related to the mechanism of aging, which provided new insights into the mechanism of aging process.
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Objective:To investigate the safety and dose of 4D template (real-time adjustable angle template) in the treatment of advanced malignant tumors with 125I seeds. Methods:98 patients with advanced malignant tumors admitted to Department of Thoracic Surgery of Shaanxi Provincial Tumor Hospital were treated with 4D template-navigated radioactive 125I seed implantation from June 2018 to December 2019. Preoperative TPS plan, intraoperative optimization, postoperative verification of immediate dose and postoperative evaluation of implantation dose were performed. The treatment results were observed. Results:All 98 patients completed the seed implantation. The implantation dose of GTV of implantation site receiving external irradiation was (12 489±414) cGy and the dose of no external irradiation was (15 036±514) cGy. V 100% was 84.7%-94.1%, and 88.2%-93.7%. The implantation dose of CTV was (7 450±621) cGy, and (9 080±761) cGy. The quality of dose implantation was evaluated as: excellent in 89 cases (91%, 89/98), good in 7 cases (7%, 7/98), fair in 2 cases (2%, 2/98), and poor in 0 case, respectively. The symptom relief rate of patients with pain was 92%(36/39). The 1-and 2-year local control rates were 61%, 36% and 82%, 54% in patients treated with and without external irradiation, respectively. The difference was statistically significant ( P=0.02). The incidence rates of pneumothorax and hemoptysis were 19%(9/48) and 10%(5/48). No corresponding complications were observed in other parts of the patients. Conclusion:4D template-assisted 125I seed therapy is safe and effective for malignant tumors, and intraoperative adjustment of needle angle and dose optimization can realize the precise control of implantation dose.
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OBJECTIVE@#To investigate the inhibitory effect of RSL3 on the proliferation, invasion and migration of cisplatinresistant testicular cancer cells (I-10/DDP) and the effect of carbenoxolone on the activity of RSL3 against testicular cancer.@*METHODS@#MTT assay was used to evaluate the survival rate of I-10/DDP cells following treatment with RSL3 (1, 2, 4, 8, 16 or 32 μmol/L) alone or in combination with carbenoxolone (100 μmol/L) or after treatment with Fer-1 (2 μmol/L), RSL3 (4 μmol/L), RSL3+Fer-1, RSL3+carbenoxolone (100 μmol/L), or RSL3+Fer-1+carbenoxolone. Colony formation assay was used to assess the proliferation ability of the treated cells; wounding-healing assay and Transwell assay were used to assess the invasion and migration ability of the cells. The expression of GPX4 was detected using Western blotting, the levels of lipid ROS were detected using C11 BODIPY 581/591 fluorescent probe, and the levels of Fe2+ were determined with FerroOrange fluorescent probe.@*RESULTS@#RSL3 dose-dependently decreased the survival rate of I-10/DDP cells, and the combined treatment with 2, 4, or 8 μmol/L RSL3 with carbenoxolone, as compared with RSL3 treatment alone, resulted in significant reduction of the cell survival rate. The combination with carbenoxolone significantly enhanced the inhibitory effect of RSL3 on colony formation, wound healing rate (P=0.005), invasion and migration of the cells (P < 0.001). Fer-1 obviously attenuated the inhibitory effects of RSL3 alone and its combination with carbenoxolone on I-10/DDP cells (P < 0.01). RSL3 treatment significantly decreased GPX4 expression (P=0.001) and increased lipid ROS level (P=0.001) and Fe2+ level in the cells, and these effects were further enhanced by the combined treatment with carbenoxolone (P < 0.01).@*CONCLUSION@#Carbenoxolone enhances the inhibitory effect of RSL3 on the proliferation, invasion and migration of cisplatin-resistant testicular cancer cells by promoting RSL3-induced ferroptosis.
Subject(s)
Humans , Male , Carbenoxolone/pharmacology , Cell Line, Tumor , Cell Proliferation , Cisplatin/pharmacology , Ferroptosis , Fluorescent Dyes/pharmacology , Lipids , Neoplasms, Germ Cell and Embryonal , Reactive Oxygen Species , Testicular NeoplasmsABSTRACT
Purpose@#To report two rare cases of Brown McLean syndrome after cataract surgery in a patient with aphakia.Case summary: (Case 1) A 54-year-old woman with Marfan’s syndrome who had aphakia and peripheral corneal edema after left eye cataract surgery 4 years ago. The patient had an elevated lesion in the peripheral cornea without involving the central cornea, and had symptoms of pain, irritation and tearing. Specular microscopy showed normal endothelial cell density and morphology in the edematous cornea. The peripheral corneal edema improved after use of antibiotics, autoserum eyedrops and 5% NaCl eyedrops. (Case 2) A 61-year-old woman with aphakia in her left eye after bilateral cataract surgery 11 years ago, underwent surgery for a macular hole in both eyes. The patient developed peripheral corneal erosions and edema in the left eye 2 months after the surgery. Specular microscopy showed normal endothelial cell density and morphology. The peripheral corneal edema was static over the years while using 5% NaCl eyedrops and artificial tears, and did not progress to involve the central cornea. @*Conclusions@#Brown McLean syndrome is a rare disease but the possibility should be considered if a patient with aphakia after cataract surgery has peripheral corneal edema for several years.
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Purpose@#To report two cases of treatment using high-frequency radio wave electrosurgery for corneal neovascularization that recurred after medication and laser photocoagulation attempts.Case summary: (Case 1) A 53-year-old man visited our hospital complaining of corneal opacity. The best-corrected visual acuity in the left eye was 0.6. Lipid keratopathy indicated new inferior vessels. There was no significant change in corneal opacity after medication and laser photocoagulation; however, the recurrence of feeder vessels was observed. Therefore, electrocautery was performed via high-frequency radio wave electrosurgery. Visual acuity, measured 1 month later, improved to 0.9. Over the subsequent 4-year observation period, new vessels did not recur and the corneal opacity decreased gradually. (Case 2) A 23-year-old woman visited complaining of left eye pain. She had undergone laser photocoagulation three times for corneal new vessels. Visual acuity in her left eye was 0.4. Recurrence of new vessels at the upper cornea was observed, and electrocautery was performed. After 2 months, corneal opacity decreased without revascularization, and visual acuity improved to 0.5. @*Conclusions@#In patients with corneal neovascularization, electrocautery using high-frequency radio wave electrosurgery is simple and effective and can reduce corneal opacity and improve vision without complications.
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Purpose@#To report two rare cases of Brown McLean syndrome after cataract surgery in a patient with aphakia.Case summary: (Case 1) A 54-year-old woman with Marfan’s syndrome who had aphakia and peripheral corneal edema after left eye cataract surgery 4 years ago. The patient had an elevated lesion in the peripheral cornea without involving the central cornea, and had symptoms of pain, irritation and tearing. Specular microscopy showed normal endothelial cell density and morphology in the edematous cornea. The peripheral corneal edema improved after use of antibiotics, autoserum eyedrops and 5% NaCl eyedrops. (Case 2) A 61-year-old woman with aphakia in her left eye after bilateral cataract surgery 11 years ago, underwent surgery for a macular hole in both eyes. The patient developed peripheral corneal erosions and edema in the left eye 2 months after the surgery. Specular microscopy showed normal endothelial cell density and morphology. The peripheral corneal edema was static over the years while using 5% NaCl eyedrops and artificial tears, and did not progress to involve the central cornea. @*Conclusions@#Brown McLean syndrome is a rare disease but the possibility should be considered if a patient with aphakia after cataract surgery has peripheral corneal edema for several years.
ABSTRACT
Purpose@#To report two cases of treatment using high-frequency radio wave electrosurgery for corneal neovascularization that recurred after medication and laser photocoagulation attempts.Case summary: (Case 1) A 53-year-old man visited our hospital complaining of corneal opacity. The best-corrected visual acuity in the left eye was 0.6. Lipid keratopathy indicated new inferior vessels. There was no significant change in corneal opacity after medication and laser photocoagulation; however, the recurrence of feeder vessels was observed. Therefore, electrocautery was performed via high-frequency radio wave electrosurgery. Visual acuity, measured 1 month later, improved to 0.9. Over the subsequent 4-year observation period, new vessels did not recur and the corneal opacity decreased gradually. (Case 2) A 23-year-old woman visited complaining of left eye pain. She had undergone laser photocoagulation three times for corneal new vessels. Visual acuity in her left eye was 0.4. Recurrence of new vessels at the upper cornea was observed, and electrocautery was performed. After 2 months, corneal opacity decreased without revascularization, and visual acuity improved to 0.5. @*Conclusions@#In patients with corneal neovascularization, electrocautery using high-frequency radio wave electrosurgery is simple and effective and can reduce corneal opacity and improve vision without complications.