Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 277
Filtrar
1.
Cell Commun Signal ; 22(1): 353, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970072

RESUMEN

Copper is a crucial trace element that plays a role in various pathophysiological processes in the human body. Copper also acts as a transition metal involved in redox reactions, contributing to the generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated in different types of regulated cell death. The recent discovery of cuproptosis, a copper-dependent regulated cell death pathway that is distinct from other known regulated cell death forms, has raised interest to researchers in the field of cancer therapy. Herein, the present work aims to outline the current understanding of cuproptosis, with an emphasis on its anticancer activities through the interplay with copper-induced oxidative stress, thereby providing new ideas for therapeutic approaches targeting modes of cell death in the future.


Asunto(s)
Antineoplásicos , Cobre , Estrés Oxidativo , Cobre/metabolismo , Humanos , Estrés Oxidativo/efectos de los fármacos , Antineoplásicos/farmacología , Animales , Especies Reactivas de Oxígeno/metabolismo , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología
2.
Anal Chem ; 96(26): 10732-10737, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38875498

RESUMEN

Measurement of infrared spectroscopy has emerged as a significant challenge for carbon materials due to the sampling problem. To overcome this issue, in this work, we performed measurements of IR spectra for carbon materials including C60, C70, diamond powders, graphene, and carbon nanotubes (CNTs) using the photoacoustic spectroscopy (PAS) technique; for comparison, the vibrational patterns of these materials were also studied with a conventional transmission method, diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, or Raman spectroscopy. We found that the IR photoacoustic spectroscopy (IR-PAS) scheme worked successfully for these carbon materials, offering advantages in sampling. Interestingly, the profiles of IR-PAS spectra for graphene and CNTs exhibit negative bands using carbon black as the reference; the negative spectral information may provide valuable knowledge about the storage energy, production, structure, defect, or impurity of graphene and CNTs. Thus, this approach may open a new avenue for analyzing carbon materials.

3.
Cancers (Basel) ; 16(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38730569

RESUMEN

BACKGROUND: We aimed to evaluate the interaction between colorectal adenoma risks among asymptomatic individuals in terms of metabolic health status and obesity, and examine the normal waist-to-hip ratio (WHR) in adults with colorectal adenoma risk. METHODS: A cross-sectional, retrospective study was conducted at MacKay Memorial Hospital involving 16,996 participants who underwent bidirectional gastrointestinal endoscopy between 2013 and 2023. The study recorded important clinicopathological characteristics, including age, body mass index and WHR, Framingham Risk Score (FRS), blood glucose level, and Helicobacter pylori (H. pylori) infection status. RESULTS: Multivariate logistic regression analysis demonstrated that elevated hemoglobin A1C (HbA1c), increased FRS, positive H. pylori infection, and WHR ≥ 0.9 are independent risk factors for colorectal adenoma. In examining the interaction between FRS and WHR using multivariate logistic regression to evaluate adenoma risk, the OR for the interaction term was 0.95, indicating a decline in adenoma risk when considering the interaction between these two factors. Incorporating HbA1c into the analysis, evaluating the interaction between FRS and WHR still demonstrated a statistically significant impact on adenoma risk (OR 0.96, p < 0.001). Participants with WHR < 0.9, elevated FRS, positive H. pylori infection, and increased HbA1c levels were associated with a higher risk of colorectal adenoma formation. Remarkably, the increased risk of adenoma due to rising HbA1c levels was statistically significant only for those with a WHR < 0.9. CONCLUSIONS: An increase in FRS and HbA1c or a positive H. pylori infection still warrants vigilance for colorectal adenoma risk when WHR is 0.9. These factors interacted with each other and were found to have a minimal decline in adenoma risk when considering the interaction between WHR and FRS.

4.
Transl Vis Sci Technol ; 13(5): 23, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38809531

RESUMEN

Purpose: To develop convolutional neural network (CNN)-based models for predicting the axial length (AL) using color fundus photography (CFP) and explore associated clinical and structural characteristics. Methods: This study enrolled 1105 fundus images from 467 participants with ALs ranging from 19.91 to 32.59 mm, obtained at National Taiwan University Hospital between 2020 and 2021. The AL measurements obtained from a scanning laser interferometer served as the gold standard. The accuracy of prediction was compared among CNN-based models with different inputs, including CFP, age, and/or sex. Heatmaps were interpreted by integrated gradients. Results: Using age, sex, and CFP as input, the mean ± standard deviation absolute error (MAE) for AL prediction by the model was 0.771 ± 0.128 mm, outperforming models that used age and sex alone (1.263 ± 0.115 mm; P < 0.001) and CFP alone (0.831 ± 0.216 mm; P = 0.016) by 39.0% and 7.31%, respectively. The removal of relatively poor-quality CFPs resulted in a slight MAE reduction to 0.759 ± 0.120 mm without statistical significance (P = 0.24). The inclusion of age and CFP improved prediction accuracy by 5.59% (P = 0.043), while adding sex had no significant improvement (P = 0.41). The optic disc and temporal peripapillary area were highlighted as the focused areas on the heatmaps. Conclusions: Deep learning-based prediction of AL using CFP was fairly accurate and enhanced by age inclusion. The optic disc and temporal peripapillary area may contain crucial structural information for AL prediction in CFP. Translational Relevance: This study might aid AL assessments and the understanding of the morphologic characteristics of the fundus related to AL.


Asunto(s)
Longitud Axial del Ojo , Redes Neurales de la Computación , Fotograbar , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Fotograbar/métodos , Anciano , Longitud Axial del Ojo/diagnóstico por imagen , Fondo de Ojo , Adulto Joven , Anciano de 80 o más Años
5.
Cancers (Basel) ; 16(6)2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38539541

RESUMEN

OBJECTIVE: In a previous study, we proved that an experienced urologist is more likely to adapt to the Hugo RAS system. Based on this, we further examine various parameters in this study. Parameters included in this study consisted of console time, functional outcomes, and oncological outcomes. MATERIALS AND METHODS: A total of 60 patients who underwent robot-assisted radical prostatectomy (RARP) performed by a single surgeon using the da Vinci (DV) system (n = 30) or the Hugo RAS system (n = 30) between March 2023 and August 2023 were included in the analysis. The intraoperative operative time was categorized into vesicourethral anastomosis time and overall console time. Functional and oncological outcomes were documented at the 1st and 3rd postoperative months. Parametric and non-parametric methods were adopted after checking skewness and kurtosis, and an α value of 5% was used to determine the significance. RESULTS: The vesicourethral anastomosis time was significantly lengthened (Hedge's g: 0.87; 95% confidence interval (CI): 0.34-1.39; J factor = 0.987). However, the overall console time was not affected. The functional (postoperative 3rd month: p = 0.130) and oncological outcomes (postoperative 3rd month: p = 0.103) were not significantly different. We also found that the adverse effect on surgical specimens and positive surgical margins was not affected (p = 0.552). CONCLUSION: During the process of adaptation, although intricate motions (such as the vesicourethral anastomosis time) would be lengthened, the overall console time would not change remarkably. In this process, the functional and oncological outcomes would not be compromised. This encourages urologists to adopt the Hugo RAS system in RARP if they have previous experiences of using the DV system, since their trifecta advantage would not be compromised.

6.
Arch Toxicol ; 98(5): 1543-1560, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38424264

RESUMEN

Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1 µg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48 h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments. Cellular and mitochondrial oxidative stress was enhanced with EXCC/cisplatin compared to the single treatments according to analyses of reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial membrane potential; in addition, cellular antioxidants, such as glutathione (GSH), and the mRNA expressions of antioxidant signaling genes (catalase and NFE2-like bZIP transcription factor 2) were downregulated. EXCC/cisplatin treatment produced more DNA damage than the single treatments, as indicated by γH2AX and 8-hydroxy-2'-deoxyguanosine levels. Moreover, several DNA repair genes for homologous recombination (HR) and non-homologous end joining (NHEJ) were downregulated in EXCC/cisplatin compared to others. The addition of the GSH precursor N-acetylcysteine, which has ROS scavenging activity, attenuated all EXCC/cisplatin-induced changes. Notably, EXCC/cisplatin showed lower antiproliferation, apoptosis, ROS induction, GSH depletion, and γH2AX DNA damage in normal cells than in bladder cancer cells. Therefore, the co-treatment of EXCC/cisplatin reduces the proliferation of bladder cancer cells via oxidative stress-mediated mechanisms with normal cell safety.


Asunto(s)
Cisplatino , Neoplasias de la Vejiga Urinaria , Humanos , Especies Reactivas de Oxígeno/metabolismo , Cisplatino/farmacología , Línea Celular Tumoral , Proliferación Celular , Apoptosis , Antioxidantes/farmacología , Daño del ADN , Caspasas/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética
7.
Int J Cardiol ; 402: 131851, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38360099

RESUMEN

BACKGROUND: Based solely on pre-ablation characteristics, previous risk scores have demonstrated variable predictive performance. This study aimed to predict the recurrence of AF after catheter ablation by using artificial intelligence (AI)-enabled pre-ablation computed tomography (PVCT) images and pre-ablation clinical data. METHODS: A total of 638 drug-refractory paroxysmal atrial fibrillation (AF) patients undergone ablation were recruited. For model training, we used left atria (LA) acquired from pre-ablation PVCT slices (126,288 images). A total of 29 clinical variables were collected before ablation, including baseline characteristics, medical histories, laboratory results, transthoracic echocardiographic parameters, and 3D reconstructed LA volumes. The I-Score was applied to select variables for model training. For the prediction of one-year AF recurrence, PVCT deep-learning and clinical variable machine-learning models were developed. We then applied machine learning to ensemble the PVCT and clinical variable models. RESULTS: The PVCT model achieved an AUC of 0.63 in the test set. Various combinations of clinical variables selected by I-Score can yield an AUC of 0.72, which is significantly better than all variables or features selected by nonparametric statistics (AUCs of 0.66 to 0.69). The ensemble model (PVCT images and clinical variables) significantly improved predictive performance up to an AUC of 0.76 (sensitivity of 86.7% and specificity of 51.0%). CONCLUSIONS: Before ablation, AI-enabled PVCT combined with I-Score features was applicable in predicting recurrence in paroxysmal AF patients. Based on all possible predictors, the I-Score is capable of identifying the most influential combination.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Humanos , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Inteligencia Artificial , Resultado del Tratamiento , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Ablación por Catéter/métodos , Recurrencia , Valor Predictivo de las Pruebas
8.
Aging (Albany NY) ; 16(1): 627-647, 2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38206305

RESUMEN

BACKGROUND: Research has demonstrated that some tumor cells can transform into drug-tolerant persisters (DTPs), which serve as a reservoir for the recurrence of the disease. The persister state in cancer cells arises due to temporary molecular reprogramming, and exploring the genetic composition and microenvironment during the development of head and neck squamous cell carcinoma (HNSCC) can enhance our comprehension of the types of cell death that HNSCC, thus identifying potential targets for innovative therapies. This project investigated lipid-metabolism-driven ferroptosis and its role in drug resistance and DTP generation in HNSCC. METHODS: High levels of FSP1 were discovered in the tissues of patients who experienced relapse after cisplatin treatment. RNA sequencing indicated that a series of genes related to lipid metabolism were also highly expressed in tissues from these patients. Consistent results were obtained in primary DTP cells isolated from patients who experienced relapse. The Cancer Genome Atlas database confirmed this finding. This revealed that the activation of drug resistance in cancer cells is influenced by FSP1, intracellular iron homeostasis, and lipid metabolism. The regulatory roles of ferroptosis suppressor protein 1 (FSP1) in HNSCC metabolic regulation were investigated. RESULTS: We generated human oral squamous cell carcinoma DTP cells (HNSCC cell line) to cisplatin and observed higher expression of FSP1 and lipid-metabolism-related targets in vitro. The shFSP1 blockade attenuated HNSCC-DTP cell stemness and downregulated tumor invasion and the metastatic rate. We found that cisplatin induced FSP1/ACSL4 axis expression in HNSC-DTPC cells. Finally, we evaluated the HNSCC CSC-inhibitory functions of iFSP1 (a metabolic drug and ferroptosis inducer) used for neo-adjuvant chemotherapy; this was achieved by inducing ferroptosis in a patient-derived xenograft mouse model. CONCLUSIONS: The present findings elucidate the link between iron homeostasis, ferroptosis, and cancer metabolism in HNSCC-DTP generation and acquisition of chemoresistance. The findings may serve as a suitable model for cancer treatment testing and prediction of precision treatment outcomes. In conclusion, this study provides clinically oriented platforms for evaluating metabolism-modulating drugs (FSP1 inhibitors) and new drug candidates of drug resistance and ferroptotic biomarkers.


Asunto(s)
Carcinoma de Células Escamosas , Ferroptosis , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Animales , Humanos , Ratones , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos/genética , Ferroptosis/genética , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Homeostasis , Hierro/uso terapéutico , Metabolismo de los Lípidos , Lípidos , Recurrencia Local de Neoplasia , Recurrencia , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Microambiente Tumoral
9.
Int J Mol Sci ; 24(24)2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38139175

RESUMEN

Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of oncogenic protein kinases for cancer therapy remains limited. Consequently, the functions of many kinase proteins in OSCC continue to be largely undetermined. In this research, we aim to disclose protein kinases that target OSCC and elaborate their roles and molecular mechanisms. Through the examination of the kinome library of radiotherapy-resistant/sensitive OSCC cell lines (HN12 and SAS), we identified a key gene, the tyrosine phosphorylation-regulated kinase 3 (DYRK3), a member of the DYRK family. We developed an in vitro cell model, composed of radiation-resistant OSCC, to scrutinize the clinical implications and contributions of DYRK3 and phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS) signaling in OSCC. This investigation involves bioinformatics and human tissue arrays. We seek to comprehend the role of DYRK3 and PAICS signaling in the development of OSCC and its resistance to radiotherapy. Various in vitro assays are utilized to reveal the essential molecular mechanism behind radiotherapy resistance in connection with the DYRK3 and PAICS interaction. In our study, we quantified the concentrations of DYRK3 and PAICS proteins and tracked the expression levels of key pluripotency markers, particularly PPAT. Furthermore, we extended our investigation to include an analysis of Glut-1, a gene recognized for its linkage to radioresistance in oral squamous cell carcinoma (OSCC). Furthermore, we conducted an in vivo study to affirm the impact of DYRK3 and PAICS on tumor growth and radiotherapy resistance, focusing particularly on the role of DYRK3 in the radiotherapy resistance pathway. This focus leads us to identify new therapeutic agents that can combat radiotherapy resistance by inhibiting DYRK3 (GSK-626616). Our in vitro models showed that inhibiting PAICS disrupts purinosome formation and influences the survival rate of radiation-resistant OSCC cell lines. These outcomes underscore the pivotal role of the DYRK3/PAICS axis in directing OSCC radiotherapy resistance pathways and, as a result, influencing OSCC progression or therapy resistance. Our findings also reveal a significant correlation between DYRK3 expression and the PAICS enzyme in OSCC radiotherapy resistance.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/metabolismo , Línea Celular Tumoral , Neoplasias de Cabeza y Cuello/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas Tirosina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo
10.
Sci Rep ; 13(1): 16672, 2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37794231

RESUMEN

This research aims to fabricate an AlSi10Mg parts using Laser Powder Bed Fusion technique with enhanced structural integrity. The prime novelty of this research work is eliminating the balling and sparring effects, keyhole and cavity formation by attaining effective melt pool formation. Modelling of the Laser Powder Bed Fusion process parameters such as Laser power, scanning speed, layer thickness and hatch spacing is carried out through Complex Proportional Assessment technique to optimize the parts' surface attributes and to overcome the defects based on the output responses such as surface roughness on scanning and building side, hardness and porosity. The laser power of 350 W, layer thickness of 30 µm, scan speed of 1133 mm/s, and hatch spacing of 0.1 mm produces significantly desirable results to achieve maximum hardness and minimum surface roughness and holding the porosity of < 1%. The obtained optimal setting from this research improves the structural integrity of the printed AlSi10Mg parts.

11.
Sensors (Basel) ; 23(19)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37836866

RESUMEN

Traditional ultrasonic testing uses a single probe or phased array probe to investigate and visualize defects by adapting certain imaging algorithms. The time-domain synthetic aperture focusing technique (T-SAFT) is an imaging algorithm that employs a single probe to scan along the test specimen in various positions, to generate inspection images with better resolution. Both the T-SAFT and phased array probes are contact methods with limited bandwidth. This work aims to combine the advantages of the T-SAFT and phased array in a noncontact way with the aid of laser ultrasonics. Here, a pulsed laser beam is employed to generate ultrasonic waves in both thermoelastic and ablation regimes, whereas the laser Doppler vibrometer is used to acquire the generated signals. These two lasers are focused on the test specimen and, to avoid the plasma and crater influence in the ablation regime, the transmission beam and reception beam are separated by 5 mm. By moving the test specimen with a step size of 0.5 mm, a 1D linear phased array (41 and 43 elements) with a pitch of 0.5 mm was synthesized, and three side-drilled holes (Ø 8 mm-thermoelastic regime, Ø 10 mm and Ø 2 mm-ablation regime) were introduced for inspection. The A-scan data obtained from these elements were processed via the T-SAFT algorithm to generate the inspection images in various grid sizes. The results showed that the defect reflections obtained in the ablation regime have better visibility than those from the thermoelastic regime. This is due to the high-amplitude signals obtained in the ablation regime, which pave the way for enhancing the pixel intensity of each grid. Moreover, the separation distance (5 mm) does not have any significant effect on the defect location during the reconstruction process.

12.
Cancers (Basel) ; 15(17)2023 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-37686563

RESUMEN

OBJECTIVE: This study aimed to explore the benefits of theranostic robot-assisted radical prostatectomy (T-RARP) for clinically highly suspicious prostate cancer (PCa) without proven biopsies. MATERIAL AND METHODS: Between February 2016 and December 2020, we included men with clinically highly suspicious PCa in this study. They were assessed to have possible localized PCa without any initial treatments, and were categorized into previous benign biopsies or without biopsies. Furthermore, another group of malignant biopsies with RARP in the same time frame was adopted as the control group. The endpoints were to compare the oncological outcome and functional outcome between malignant biopsies with RARP and T-RARP. p < 0.05 was considered to be significant. RESULTS: We included 164 men with proven malignant biopsies treated with RARP as the control group. For T-RARP, we included 192 men. Among them, 129 were preoperatively benign biopsies, and 63 had no biopsies before T-RARP. Approximately 75% of men in the T-RARP group had malignant pathology in their final reports, and the other 25% had benign pathology. T-RARP provides several oncological advantages, such as a higher initial pathological T stage, lower Gleason grade, and lower odds of positive surgical margins. However, the biochemical recurrence rates were not significantly decreased. From our cohort, T-RARP (odds ratio with 95% confidence interval; erectile recovery: 3.19 (1.84-5.52), p < 0.001; continence recovery: 2.25 (1.46-3.48), p < 0.001) could result in better recovery of functional outcomes than malignant biopsies with RARP. CONCLUSIONS: For clinically highly suspicious PCa, T-RARP was able to detect around 75% of PCa cases and preserved their functional outcomes maximally. However, in 25% of men with benign pathology, approximately 6% would have incontinence and 10% would have erectile impairment. This part should be sufficiently informed of the potential groups considering T-RARP.

13.
Int J Med Robot ; : e2577, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37705314

RESUMEN

BACKGROUND: Among the novel robotic platforms, the Hugo RAS system is the second most studied platform, next to the da Vinci system, and we aim to address our experiences in radical prostatectomy (RP) with the Hugo RAS system. METHODS: We recorded our first 12 cases of prostate cancer undergoing RP with the Hugo RAS system. The median console time was 145 min and median hospital stay was 7 days. Hedge' g was applied to search for the cut-off case in four parameters in surgeries. RESULTS: Pre-console preparation was significantly improved after the first seven cases, and the console time was remarkably shortened after the first two cases. The intraoperative pause for trouble shooting was remarkably shortened after the first three cases. CONCLUSIONS: We found that RP with the Hugo RAS system was feasible, and the learning curve was short as surgeons may benefit from the previous experience with the da Vinci system.

14.
Biomed Pharmacother ; 164: 114962, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37276643

RESUMEN

Bladder cancer is known as one of the top ten most common cancer types worldwide and can be majorly divided into muscles invasive bladder cancer (MIBC) and non-muscles invasive type (NMIBC). However, the prognosis of BC remains poor under standard treatment including radical cystectomy or concurrent chemoradiotherapy. Numerous studies have reported that the prognosis of BC is associated with the activation of signal transducer and activator of transcription (STAT3) and nuclear factor kappa-B (NF-κB). Fluoxetine, a well-known anti-depressant, has been reported to against various type of cancers. However, it is unclear whether fluoxetine has the capacity to inhibit BC progression by targeting STAT3 and NF-κB-mediated signaling. Here, we used cell viability, apoptosis assay, wound healing assay, invasion/migration assay, Western blotting assay, immunofluorescence staining, as well as animal experiments, to elucidate the efficacy of fluoxetine on in vitro and in vivo BC models. We found that fluoxetine may induce cytotoxicity and intrinsic/extrinsic apoptosis in BC and enhance the potential of cisplatin. Fluoxetine promoted both caspase-dependent and caspase-independent apoptosis signaling by activating caspase-3, 8, 9, apoptosis-inducing factor (AIF), and EndG. Furthermore, fluoxetine suppressed invasion and migration ability and the expression of metastasis-associated genes. Fluoxetine was also found to inactivate the phosphorylation of STAT3 (Tyr705) and NF-κB (Ser536) and suppress the nuclear translocation of NF-κB. In MB49-bearing mice, fluoxetine effectively delayed the progression of BC without inducing general toxicity. In summary, the induction of apoptosis and the inhibition of invasion triggered by fluoxetine are associated with the inactivation of STAT3 and NF-κB.


Asunto(s)
FN-kappa B , Neoplasias de la Vejiga Urinaria , Animales , Ratones , FN-kappa B/metabolismo , Cisplatino/farmacología , Cisplatino/metabolismo , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Línea Celular Tumoral , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Apoptosis , Caspasas/metabolismo , Factor de Transcripción STAT3/metabolismo
15.
Curr Oncol ; 30(5): 5093-5102, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37232843

RESUMEN

Urothelial carcinoma (UC) could be observed in urinary bladder (UBUC) and upper urinary tracts (UTUC). In the National Comprehensive Cancer Network guidelines for bladder cancer, extirpative surgery is indicated in certain cases. However, some extreme cases might also need the extirpation of the majority of the urinary tract, which is called complete urinary tract extirpation (CUTE). We present a patient diagnosed with high-grade UBUC and UTUC. He underwent dialysis for end-stage renal disease (ESRD) at the same time. Considering his non-functional kidneys and removing his high-risk urothelium at the same time, we performed robot-assisted CUTE to extirpate both his upper urinary tracts, urinary bladder, and prostate. In our experience, the console time was not significantly elongated, and the perioperative course was uneventful. To our knowledge, this is the first case report adopting a robotic system in such an extreme case. We conclude that robot-assisted CUTE is worth further study regarding its oncological survival outcomes and perioperative safety in patients with ESRD on dialysis.


Asunto(s)
Carcinoma de Células Transicionales , Fallo Renal Crónico , Robótica , Neoplasias de la Vejiga Urinaria , Sistema Urinario , Masculino , Humanos , Neoplasias de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/cirugía , Carcinoma de Células Transicionales/patología , Diálisis Renal , Sistema Urinario/patología , Fallo Renal Crónico/patología , Fallo Renal Crónico/cirugía
16.
ACS Synth Biol ; 12(5): 1424-1436, 2023 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-37058298

RESUMEN

Fluorescence microscopy imaging of specific chromosomal sites is essential for genome architecture research. To enable visualization of endogenous loci in mammalian cells, programmable DNA-binding proteins such as TAL effectors and CRISPR/dCas9 are commonly utilized. In addition, site-specific insertion of a TetO repeat array, coupled with TetR-enhanced green fluorescent protein fusion protein expression, can be used for labeling nonrepetitive endogenous loci. Here, we performed a comparison of several live-cell chromosome tagging methods, including their effect on subnuclear positioning, expression of adjacent genes, and DNA replication timing. Our results showed that the CRISPR-based imaging method can delay DNA replication timing and sister chromatid resolution at certain region. However, subnuclear localization of the labeled locus and gene expression from adjacent loci were unaffected by either TetO/TetR or CRISPR-based methods, suggesting that CRISPR-based imaging could be used for applications that do not require DNA replication analysis.


Asunto(s)
Sistemas CRISPR-Cas , Momento de Replicación del ADN , Animales , Sistemas CRISPR-Cas/genética , Cromosomas , Genoma , Proteínas de Unión al ADN , Chaperonas Moleculares , Mamíferos
17.
Sci Rep ; 13(1): 6800, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37100933

RESUMEN

The additive manufacturing technique of material extrusion has challenge of excessive process defects and not achieving the desired mechanical properties. The industry is trying to develop certification to better control variations in mechanical attributes. The current study is a progress towards understanding the evolution of processing defects and the correlation of mechanical behavior with the process parameters. Modeling of the 3D printing process parameters such as layer thickness, printing speed, and printing temperature is carried out through L27 orthogonal array using Taguchi approach. In addition, CRITIC embedded WASPAS is adopted to optimize the parts' mechanical attributes and overcome the defects. Flexural and tensile poly-lactic acid specimens are printed according to ASTM standards D790 and D638, respectively, and thoroughly analyzed based on the surface morphological analysis to characterize defects. The parametric significance analysis is carried out to explore process science where the layer thickness, print speed, and temperature significantly control the quality and strength of the parts. Mathematical optimization results based on composite desirability show that layer thickness of 0.1 mm, printing speed of 60 mm/s, and printing temperature of 200 °C produce significantly desirable results. The validation experiments yielded the maximum flexural strength of 78.52 MPa, the maximum ultimate tensile strength of 45.52 MPa, and maximum impact strength of 6.21 kJ/m2. It is established that multiple fused layers restricted the propagation of cracks with minimum thickness due to enhanced diffusion between the layers.

18.
Curr Oncol ; 30(2): 1699-1707, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36826092

RESUMEN

Currently, the active surveillance of men with favorable intermediate-risk localized prostate cancer (PCa) is a longstanding controversy, in terms of their oncological outcomes, and radical prostatectomy would constitute a similar concern of overtreatment, regarding its functional outcomes. Thus, focal therapy could be considered in men belonging to favorable intermediate-risk group. Among all focal therapies, high-intensity focused ultrasound (HIFU) was the most studied methodology in clinical trials. Although HIFU provided better functional outcomes than radical prostatecomy, the oncological outcomes were inferior in men with intermediate-risk localized PCa. Two articles have been published discussing the feasibility and clinical outcomes of robot-assisted partial prostatectomy (RAPP), and both the functional and oncological outcomes were superior than those with HIFU. However, the rate of positive surgical margins (PSMs) was reported as high in the literature. Here, we present a case of favorable intermediate-risk localized PCa with an isolated tumor at the anterior apex. After reconstructing a personal three-dimensional (3D) image, we utilized it in a 3D image-guided precise excise, followed by intraoperative frozen specimen review. We found that this method may present a resolution to the high PSM rate documented in the current literature regarding RAPP. This method merits further study with a well-designed prospective study.


Asunto(s)
Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Robótica , Realidad Virtual , Masculino , Humanos , Estudios Prospectivos , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias de la Próstata/patología , Prostatectomía/métodos
19.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36614220

RESUMEN

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.


Asunto(s)
Induración Peniana , Masculino , Humanos , Induración Peniana/tratamiento farmacológico , Pene , Erección Peniana , Inyecciones , Células Madre
20.
Hu Li Za Zhi ; 70(4): 32-43, 2023 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39084891

RESUMEN

BACKGROUND: The 2005 revision of the code of ethics for nurses has been in effect in Taiwan for more than 17 years. Although this code has been smoothly implemented during this time, changing social expectations and ethical perspectives, advancements in science and technology, and the evolution of the nurse-patient relationship suggest this code should be once again be updated. PURPOSE: This study was conducted to suggest revisions to the Taiwan code of ethics for nurses necessary to meet current needs and address social and medical care environment trends. METHODS: A multivariate research approach was adopted. The classification of the code of ethics for nurses norms in six international nursing organizations and evidence-based ethical and philosophical thinking literature were referenced, with the main notification demands incorporated into the Ministry of Health and Welfare's Nursing Workplace Controversy Reporting Platform. After drafting the aspects and provisions of Taiwan code of ethics for nurses norms, expert review procedures such as focus groups, Delphi expert consensus, and public forums were conducted. RESULTS: After three expert focus group discussion rounds, a structured questionnaire was completed, and 50 Delphi experts in six fields completed the online questionnaire. After the second consensus round, the importance and clarity of the 47 ethical code provisions in the four aspects were determined with 100% and 99.8% agreement reached, indicating no significant difference in scores between the multidisciplinary expert group and the ethical code. The resulting revision proposed for the Taiwan code of ethics for nurses includes: nursing staff and care recipients (14 provisions), nursing staff and practice (13 provisions), nursing staff and the profession (10 provisions), and nursing staff and society (10 provisions). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: In terms of education, the revised Taiwan code of ethics for nurses should be integrated into the nursing education curriculum of nursing colleges and used as teaching material for the continuing education of nurses. In terms of policy, these norms should be included as evaluation benchmarks and inspection items for hospitals. In addition, the attention and support of senior managers in institutions must be secured and a handling protocol for moral dilemma cases and related consultation mechanisms must be established. Nursing supervisors should be guided to develop the ability to address these dilemmas to help foster a positive workplace and a respectful team atmosphere. All professional groups should participate actively in promoting issues related to nursing ethics, organize seminars and continuing education activities, and make the revised Taiwan code of ethics for nurses and learning cases available online for reference by nursing staff nationwide.


Asunto(s)
Códigos de Ética , Ética en Enfermería , Humanos , Taiwán
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA