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1.
Mol Cancer Ther ; : OF1-OF11, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38853421

RESUMEN

Most patients with lung squamous cell carcinoma (LSCC) undergo chemotherapy, radiotherapy, and adjuvant immunotherapy for locally advanced disease. The efficacy of these treatments is still limited because of dose-limiting toxicity or locoregional recurrence. New combination approaches and targets such as actionable oncogenic drivers are needed to advance treatment options for patients with LSCC. Moreover, other options for chemotherapy-ineligible patients are limited. As such, there is a critical need for the development of selective and potent chemoradiosensitizers for locally advanced LSCC. In this study, we investigated inhibiting TRAF2- and NCK-interacting protein kinase (TNIK), which is amplified in 40% of patients with LSCC, as a strategy to sensitize LSCC tumors to chemotherapy and radiotherapy. Employing a range of human LSCC cell lines and the TNIK inhibitor NCB-0846, we investigated the potential of TNIK as a chemo- and radiosensitizing target with in vitro and in vivo preclinical models. The combination of NCB-0846 with cisplatin or etoposide was at best additive. Interestingly, pre-treating LSCC cells with NCB-0846 prior to ionizing radiation (IR) potentiated the cytotoxicity of IR in a TNIK-specific fashion. Characterization of the radiosensitization mechanism suggested that TNIK inhibition may impair the DNA damage response and promote mitotic catastrophe in irradiated cells. In a subcutaneous xenograft in vivo model, pretreatment with NCB-0846 significantly enhanced the efficacy of IR and caused elevated necrosis in TNIKhigh LK2 tumors but not TNIKlow KNS62 tumors. Overall, these results indicate that TNIK inhibition may be a promising strategy to increase the efficacy of radiotherapy in patients with LSCC with high TNIK expression.

2.
Turk J Ophthalmol ; 54(2): 83-89, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38645613

RESUMEN

Objectives: To review the current literature related to the correlation between translaminar pressure difference (TLPD) and glaucoma. Materials and Methods: In this article, we conducted a literature review using MEDLINE via PubMed, Cochrane Eyes and Vision, and Google Scholar from 01/01/2010 to 31/12/2022. Search terms included "glaucoma", "intraocular pressure", "translaminar cribrosa pressure gradient/difference", "intracranial pressure", and "cerebrospinal fluid pressure". Of 471 results, 8 articles were selected for the meta-analysis. Results: Our meta-analysis demonstrated significantly higher intraocular pressure, lower cerebrospinal fluid pressure (CSFp), and greater TLPD in high-tension and normal-tension glaucoma groups compared to healthy groups. Conclusion: The differences in CSFp and TLPD between glaucoma and healthy people detected in current studies suggests a potential relationship between TLPD and glaucoma.


Asunto(s)
Presión Intraocular , Enfermedades del Nervio Óptico , Humanos , Presión Intraocular/fisiología , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/etiología , Enfermedades del Nervio Óptico/fisiopatología , Presión del Líquido Cefalorraquídeo/fisiología , Glaucoma/fisiopatología , Tonometría Ocular , Glaucoma de Baja Tensión/fisiopatología , Glaucoma de Baja Tensión/diagnóstico
3.
Mol Cancer Ther ; 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38670554

RESUMEN

Most patients with lung squamous cell carcinoma (LSCC) undergo chemotherapy, radiotherapy, and adjuvant immunotherapy for locally advanced disease. The efficacy of these treatments is still limited due to dose-limiting toxicity or locoregional recurrence. New combination approaches and targets such as actionable oncogenic drivers are needed to advance treatment options for LSCC patients. Moreover, other options for chemotherapy-ineligible patients are also limited. As such there is a critical need for the development of selective and potent chemoradiosensitizers for locally advanced LSCC. Here, we investigated inhibiting TRAF2 and NCK-interacting protein kinase (TNIK), which is amplified in 40% of LSCC patients, as a strategy to sensitize LSCC tumors to chemo- and radiotherapy. Employing a range of human LSCC cell lines and the TNIK inhibitor NCB-0846, we investigated the potential of TNIK as a chemo- and radiosensitizing target with in vitro and in vivo preclinical models. The combination of NCB-0846 with cisplatin or etoposide was at best additive. Interestingly, pre-treating LSCC cells with NCB-0846 prior to ionizing radiation (IR) potentiated the cytotoxicity of IR in a TNIK-specific fashion. Characterization of the radiosensitization mechanism suggested that TNIK inhibition may impair the DNA damage response and promote mitotic catastrophe in irradiated cells. In a subcutaneous xenograft in vivo model, pretreatment with NCB-0846 significantly enhanced the efficacy of IR and caused elevated necrosis in TNIKhigh LK2 tumors but not TNIKlow KNS62 tumors. Overall, these results indicate that TNIK inhibition may be a promising strategy to increase the efficacy of radiotherapy in LSCC patients with high TNIK expression.

4.
Clin Ter ; 175(2): 135-143, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38571472

RESUMEN

Background: Recently, cold atmospheric plasma (CAP), as well as adipose mesenchymal stem cells derived exosomes (ADMSCs-EX), have been applied separately to wound healing treatment. However, no study has investigated the additive effect on the healing mechanism of these two methods in the same skin lesion treatment model. Aim: We conduct this study to describe the results of using CAP and human ADMSCs-EX on in vitro wound healing. Methods: Exosomes were isolated from donor adipose tissue samples by ultracentrifugation method, characterized by transmission electron microscopy (TEM) and Western blot. Assessment in vitro wound healing on proliferation and migration evaluation experiments on human fibroblasts with culture medium supplemented with 10µg total exosomal proteins/1 mL and irradiated with CAP with an intensity of 30 seconds/cm2. Results: Experimental results to evaluate the ability to stimulate fibroblast migration, showed that cell migration speed in the group supplemented with ADMSCs-EX was equivalent to the group with a combination of CAP and ADMSCs-EX and had the highest rate with 87.8 ± 4.2 % and 84.4 ± 5.3 % while in the control group it was the lowest with 61.9 ± 11.4% (p<0.05). The group supplemented with CAP gave fibroblast proliferation and migration results similar to the control group (p>0.05), showing the safety of CAP with the growth of the cells. Conclusions: Therefore, in animal models, we intend to use a combination of these two therapies by using ADMSCs-EX injection therapy into the dermis at the wound edge to avoid the impact of CAP affecting the cell proliferation.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Gases em Plasma , Animales , Humanos , Gases em Plasma/farmacología , Tejido Adiposo , Cicatrización de Heridas
5.
JAMA Netw Open ; 7(2): e240465, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38411962

RESUMEN

Importance: Candidate gene analysis approaches have shown that colorectal cancer (CRC) risk attributable to diet may differ according to genotype. A genome-wide approach further allows for the exploration of underlying pathways for associations between diet and CRC risk across the genome. Objectives: To identify genetic variants that modify diet-CRC associations and to further explore the underlying pathways in the cause of CRC. Design, Setting, and Participants: This nested case-control study used data on White British participants from the prospective cohort UK Biobank. Participants were recruited between March 13, 2006, and October 1, 2010, and data were censored June 25, 2021. Exposures: The average frequency intake of 11 dietary factors in the year preceding baseline was obtained via a touchscreen questionnaire. After quality control for more than 93 million variants of imputed genetic data, 4 122 345 variants remained. Main Outcomes and Measures: Colorectal cancer cases were identified according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Genome-wide interaction analysis was performed to test interactions between dietary factors and variants using a conditional logistic regression model. Summary statistics of interactions at the variant level were used to calculate empirical P values for interactions at gene and gene-set levels in gene-based and gene-set enrichment analyses. Results: A total of 4686 participants with CRC (mean [SD] age, 60.7 [6.6] years; 2707 men [57.8%]) received a new diagnosis during a median of 12.4 years (IQR, 11.6-13.1 years) of follow-up. Once a case was detected, 3 matched controls were identified, for a total of 14 058 controls (mean [SD] age, 60.4 [6.6] years; 8121 men [57.8%]). A total of 324 variants were identified that interacted with diet consumption at the suggestive threshold (P < 1 × 10-5). In gene-based analysis, aggregation of multiple EPDR1 gene variants was found to interact with fish intake regarding CRC risk. Furthermore, gene-set enrichment analysis found that several sets of protein-coding genes, which were overrepresented with particular functions and pathways, interacted with the consumption of milk (ART), cheese (OR), tea (KRT), and alcohol (PRM and TNP). Conclusions and Relevance: In this nested case-control study, the risk of CRC associated with fish intake was modified by multiple single-nucleotide polymorphisms of the EPDR1 gene. The findings further suggested possible functions and pathways that might link the consumption of milk, cheese, tea, and alcohol with CRC development.


Asunto(s)
Bancos de Muestras Biológicas , Neoplasias Colorrectales , Animales , Masculino , Humanos , Persona de Mediana Edad , Estudios de Casos y Controles , Estudios Prospectivos , Biobanco del Reino Unido , Etanol , Ingestión de Alimentos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética ,
6.
Bioengineering (Basel) ; 11(2)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38391650

RESUMEN

Transforaminal lumbar interbody fusion (TLIF) is a commonly used technique for treating lumbar degenerative diseases. In this study, we developed a fully computer-supported pipeline to predict both the cage height and the degree of lumbar lordosis subtraction from the pelvic incidence (PI-LL) after TLIF surgery, utilizing preoperative X-ray images. The automated pipeline comprised two primary stages. First, the pretrained BiLuNet deep learning model was employed to extract essential features from X-ray images. Subsequently, five machine learning algorithms were trained using a five-fold cross-validation technique on a dataset of 311 patients to identify the optimal models to predict interbody cage height and postoperative PI-LL. LASSO regression and support vector regression demonstrated superior performance in predicting interbody cage height and postoperative PI-LL, respectively. For cage height prediction, the root mean square error (RMSE) was calculated as 1.01, and the model achieved the highest accuracy at a height of 12 mm, with exact prediction achieved in 54.43% (43/79) of cases. In most of the remaining cases, the prediction error of the model was within 1 mm. Additionally, the model demonstrated satisfactory performance in predicting PI-LL, with an RMSE of 5.19 and an accuracy of 0.81 for PI-LL stratification. In conclusion, our results indicate that machine learning models can reliably predict interbody cage height and postoperative PI-LL.

7.
Eur Urol Oncol ; 7(2): 241-247, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37558543

RESUMEN

BACKGROUND: Standard of care management for synchronous metastatic castration-sensitive prostate cancer (mCSPC) includes androgen deprivation therapy with a second-generation antiandrogen therapy and/or docetaxel. Recently, randomized data have demonstrated that prostate-directed therapy (PDT) is associated with an improvement in overall survival (OS) among patients with low-volume metastatic disease. Tumor genomics represents an additional dimension to define the clinical trajectory of patients with mCSPC. OBJECTIVE: To evaluate a high-risk (HiRi) genomic signature to predict the benefit from PDT. DESIGN, SETTING, AND PARTICIPANTS: We performed a single-institution retrospective review of men with synchronous low-volume mCSPC who underwent DNA panel sequencing of their tumor. Patients were classified according to the presence of HiRi mutation including pathogenic mutations in TP53, ATM, BRCA1, BRCA2, or Rb1. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was to determine the effect of PDT on OS in patients with and without a HiRi mutation. A survival analysis was performed with the Kaplan-Meier method compared with log-rank test and multivariable Cox regression. The interaction between HiRi mutation and PDT was evaluated. RESULTS AND LIMITATIONS: A total of 101 patients with synchronous low-volume CSPC were included with a median follow-up of 44 mo. Approximately half of patients were found to have a HiRi pathogenic mutation (49%). Patients with HiRi mutations demonstrated median OS of 73 versus 66.8 mo (p = 0.3) for no PDT versus PDT. Conversely, patients without a HiRi mutation demonstrated a significant improvement in OS of 60 versus 105.3 mo (p < 0.001) for no PDT versus PDT. The p value for interaction for OS between PDT and HiRi mutation was statistically significant (p < 0.001). Limitations include the retrospective nature of the study. CONCLUSIONS: Here, we have identified a HiRi genomic biomarker that appears predictive for the lack of benefit from PDT in men with synchronous low-volume mCSPC. Further work validating these results is warranted. PATIENT SUMMARY: In this report, we evaluated a high-risk genomic biomarker to predict the benefit from prostate-directed therapy for men with synchronous low-volume metastatic castration-sensitive prostate cancer. We found that men without a high-risk mutation appear to experience a greater clinical benefit from prostate-directed therapy than those with a high-risk mutation.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Próstata/cirugía , Próstata/patología , Antagonistas de Andrógenos/uso terapéutico , Estudios Retrospectivos , Biomarcadores de Tumor/genética , Castración
8.
Prostate ; 84(1): 87-99, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37812042

RESUMEN

PURPOSE: Despite well-informed work in several malignancies, the phenotypic effects of TP53 mutations in metastatic castration-sensitive prostate cancer (mCSPC) progression and metastasis are not clear. We characterized the structure-function and clinical impact of TP53 mutations in mCSPC. PATIENTS AND METHODS: We performed an international retrospective review of men with mCSPC who underwent next-generation sequencing and were stratified according to TP53 mutational status and metastatic burden. Clinical outcomes included radiographic progression-free survival (rPFS) and overall survival (OS) evaluated with Kaplan-Meier and multivariable Cox regression. We also utilized isogenic cancer cell lines to assess the effect of TP53 mutations and APR-246 treatment on migration, invasion, colony formation in vitro, and tumor growth in vivo. Preclinical experimental observations were compared using t-tests and ANOVA. RESULTS: Dominant-negative (DN) TP53 mutations were enriched in patients with synchronous (vs. metachronous) (20.7% vs. 6.3%, p < 0.01) and polymetastatic (vs. oligometastatic) (14.4% vs. 7.9%, p < 0.01) disease. On multivariable analysis, DN mutations were associated with worse rPFS (hazards ratio [HR] = 1.97, 95% confidence interval [CI]: 1.31-2.98) and overall survival [OS] (HR = 2.05, 95% CI: 1.14-3.68) compared to TP53 wild type (WT). In vitro, 22Rv1 TP53 R175H cells possessed stronger migration, invasion, colony formation ability, and cellular movement pathway enrichment in RNA sequencing analysis compared to 22Rv1 TP53 WT cells. Treatment with APR-246 reversed the effects of TP53 mutations in vitro and inhibited 22Rv1 TP53 R175H tumor growth in vivo in a dosage-dependent manner. CONCLUSIONS: DN TP53 mutations correlated with worse prognosis in prostate cancer patients and higher metastatic potential, which could be counteracted by APR-246 treatment suggesting a potential future therapeutic avenue.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Pronóstico , Supervivencia sin Progresión , Mutación , Relación Estructura-Actividad , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Proteína p53 Supresora de Tumor/genética
9.
Traffic Inj Prev ; 25(3): 425-433, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38117530

RESUMEN

OBJECTIVE: This study investigates traffic safety perceptions of motorcyclists and car drivers toward risky bus driving behaviors (RBDBs) in mixed traffic flow (MTF). METHODS: The study identified 10 RBDBs and employed images in a unique questionnaire survey. Further, permutation tests were employed to compare perceptions of motorcyclists in scenarios involving bus-motorcycle-car flow and bus-motorcycle flow and to compare their perceptions to those of car drivers'. Moreover, heteroskedastic generalized ordered logit regression models were utilized to predict traffic safety perceptions of motorcyclists and car drivers toward RBDBs. RESULTS: High-speed bus driving is perceived as the most dangerous situation, while continuous flashing of lights at vehicles in front is perceived as the least dangerous. The permutation test revealed that motorcyclists tend to perceive RBDBs as less dangerous in bus-motorcycle flow than in mixed flow with cars, while car drivers consider them safer than motorcyclists. The regression model revealed that among the RBDBs, bus moving at high speeds, abruptly overtaking, abruptly changing lanes, and suddenly pulling over at bus stops are perceived as the most dangerous by motorcyclists and car drivers. The study also discusses the relationships between the socio-demographic characteristics of motorcyclists/car drivers and their safety perception toward RBDBs. CONCLUSIONS: These findings could inform the development of interventions to reduce RBDBs and improve traffic safety for motorcyclists and car drivers.


Asunto(s)
Conducción de Automóvil , Humanos , Accidentes de Tránsito/prevención & control , Automóviles , Vehículos a Motor , Motocicletas
10.
BMC Cancer ; 23(1): 993, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853340

RESUMEN

BACKGROUND: This study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk. METHODS: We analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term. RESULTS: During a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05-1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18-1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HRT3vsT1 = 2.12, 95% CI = 1.97-2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08-1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00-1.19 for low vs. high WCRF dietary scores). CONCLUSION: Dietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk.


Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/genética , Estudios Prospectivos , Bancos de Muestras Biológicas , Estilo de Vida , Factores de Riesgo , Dieta , Ingestión de Alimentos , Reino Unido/epidemiología
11.
ACS Omega ; 8(21): 19119-19127, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37273580

RESUMEN

Synthetic design allowing predictive control of charge transfer and other optoelectronic properties of Lewis acid adducts remains elusive. This challenge must be addressed through complementary methods combining experimental with computational insights from first principles. Ab initio calculations for optoelectronic properties can be computationally expensive and less straightforward than those sufficient for simple ground-state properties, especially for adducts of large conjugated molecules and Lewis acids. In this contribution, we show that machine learning (ML) can accurately predict density functional theory (DFT)-calculated charge transfer and even properties associated with excited states of adducts from readily obtained molecular descriptors. Seven ML models, built from a dataset of over 1000 adducts, show exceptional performance in predicting charge transfer and other optoelectronic properties with a Pearson correlation coefficient of up to 0.99. More importantly, the influence of each molecular descriptor on predicted properties can be quantitatively evaluated from ML models. This contributes to the optimization of a priori design of Lewis adducts for future applications, especially in organic electronics.

12.
Environ Res ; 231(Pt 1): 115984, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37156354

RESUMEN

In the quest of improving the photocatalytic efficiency of photocatalysts, the combination of two and more semiconductors recently has garnered significant attention among scientists in the field. The doping of conductive metals is also an effective pathway to improve photocatalytic performance by avoiding electron/hole pair recombination and enhancing photon energy absorption. This work presented a design and fabrication of porphyrin@g-C3N4/Ag nanocomposite using acid-base neutralization-induced self-assembly approach from monomeric porphyrin and g-C3N4/Ag material. g-C3N4/Ag material was synthesized by a green reductant of Cleistocalyx operculatus leaf extract. Electron scanning microscopy (SEM), X-ray diffraction (XRD), FT-IR spectroscopy, and UV-vis spectrometer were utilized to analyse the properties of the prepared materials. The prepared porphyrin@g-C3N4/Ag nanocomposite showed well integration of porphyrin nanostructures on the g-C3N4/Ag's surface, in which porphyrin nanofiber was of the diameter in nanoscales and the length of several micrometers, and Ag NPs had an average particle size of less than 20 nm. The photocatalytic behavior of the resultant nanocomposite was tested for the degradation of Rhodamine B dye, which exhibited a remarkable RhB photodegrading percentage. The possible mechanism for photocatalysis of the porphyrin@g-C3N4/Ag nanocomposite toward Rhodamine B dye was also proposed and discussed.


Asunto(s)
Nanocompuestos , Porfirinas , Espectroscopía Infrarroja por Transformada de Fourier , Colorantes , Electrones
13.
Diagnostics (Basel) ; 13(6)2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36980400

RESUMEN

OBJECTIVE: In this systematic review, we summarized the indications for and outcomes of three main unilateral biportal endoscopic (UBE) approaches for the decompression of degenerative lumbar spinal stenosis (DLSS). METHODS: A comprehensive search of the literature was performed using Ovid Embase, PubMed, Web of Science, and Ovid's Cochrane Library. The following information was collected: surgical data; patients' scores on the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Macnab criteria; and surgical complications. RESULTS: In total, 23 articles comprising 7 retrospective comparative studies, 2 prospective comparative studies, 12 retrospectives case series, and 2 randomized controlled trials were selected for quantitative analysis. The interlaminar approach for central and bilateral lateral recess stenoses, contralateral approach for isolated lateral recess stenosis, and paraspinal approach for foraminal stenosis were used in 16, 2, and 4 studies, respectively. In one study, both interlaminar and contralateral approaches were used. L4-5 was the most common level decompressed using the interlaminar and contralateral approaches, whereas L5-S1 was the most common level decompressed using the paraspinal approach. All three approaches provided favorable clinical outcomes at the final follow-up, with considerable improvements in patients' VAS scores for leg pain (63.6-73.5%) and ODI scores (67.2-71%). The overall complication rate was <6%. CONCLUSIONS: The three approaches of UBE surgery are effective and safe for the decompression of various types of DLSS. In the future, long-term prospective studies and randomized control trials are warranted to explore this new technique further and to compare it with conventional surgical techniques.

16.
Mol Cancer Ther ; 22(4): 519-528, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-36752776

RESUMEN

Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to form bipolar mitotic spindles. The aim of this study was to investigate whether centrosome clustering (CC) inhibition (CCi) would preferentially radiosensitize non-small cell lung cancer (NSCLC). Griseofulvin (GF; FDA-approved treatment) inhibits CC, and combined with radiation treatment (RT), resulted in a significant increase in the number of NSCLC cells with multipolar spindles, and decreased cell viability and colony formation ability in vitro. In vivo, GF treatment was well tolerated by mice, and the combined therapy of GF and radiation treatment resulted in a significant tumor growth delay. Both GF and radiation treatment also induced the generation of micronuclei (MN) in vitro and in vivo and activated cyclic GMP-AMP synthase (cGAS) in NSCLC cells. A significant increase in downstream cGAS-STING pathway activation was seen after combination treatment in A549 radioresistant cells that was dependent on cGAS. In conclusion, GF increased radiation treatment efficacy in lung cancer preclinical models in vitro and in vivo. This effect may be associated with the generation of MN and the activation of cGAS. These data suggest that the combination therapy of CCi, radiation treatment, and immunotherapy could be a promising strategy to treat NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Ratones , Griseofulvina/farmacología , Griseofulvina/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/patología , Centrosoma , Nucleotidiltransferasas
17.
BMC Microbiol ; 23(1): 33, 2023 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-36709262

RESUMEN

BACKGROUND: Differences in the composition and diversity of the gut microbial communities among individuals are influenced by environmental factors. However, there is limited research on factors affecting microbiome variation in colorectal cancer patients, who display lower inter-individual variations than that of healthy individuals. In this study, we examined the association between modifiable factors and the microbiome variation in colorectal cancer patients. METHODS: A total of 331 colorectal cancer patients who underwent resection surgery at the Department of Surgery, Seoul National University Hospital between October 2017 and August 2019 were included. Fecal samples from colorectal cancer patients were collected prior to the surgery. Variations in the gut microbiome among patients with different lifestyles and metabolic diseases were examined through the network analysis of inter-connected microbial abundance, the assessment of the Anna Karenina principle effect for microbial stochasticity, and the identification of the enriched bacteria using linear discrimination analysis effect size. Associations of dietary diversity with microbiome variation were investigated using the Procrustes analysis. RESULTS: We found stronger network connectivity of microbial communities in non-smokers, non-drinkers, obese individuals, hypertensive subjects, and individuals without diabetes than in their counterparts. The Anna Karenina principle effect was found for history of smoking, alcohol consumption, and diabetes (with significantly greater intra-sample similarity index), whereas obesity and hypertension showed the anti-Anna Karenina principle effect (with significantly lower intra-sample similarity index). We found certain bacterial taxa to be significantly enriched in patients of different categories of lifestyles and metabolic diseases using linear discrimination analysis. Diversity of food and nutrient intake did not shape the microbial diversity between individuals (pProcrustes>0.05). CONCLUSIONS: Our findings suggested an immune dysregulation and a reduced ability of the host and its microbiome in regulating the community composition. History of smoking, alcohol consumption, and diabetes were shown to affect partial individuals in shifting new microbial communities, whereas obesity and history of hypertension appeared to affect majority of individuals and shifted to drastic reductions in microbial compositions. Understanding the contribution of modifiable factors to microbial stochasticity may provide insights into how the microbiome regulates effects of these factors on the health outcomes of colorectal cancer patients.


Asunto(s)
Neoplasias Colorrectales , Enfermedades Metabólicas , Microbiota , Humanos , Microbiota/genética , Bacterias/genética , Obesidad , Estilo de Vida
19.
Clin Exp Optom ; 106(4): 427-430, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-35188078

RESUMEN

CLINICAL RELEVANCE: Myopia prevention and anti-myopia treatment is of great importance in South East Asia. BACKGROUND: To evaluate the prevalence and related factors of myopic retinopathy in Vietnam. METHODS: A cross-sectional study was conducted on 168 eyes of 88 patients with high myopia presenting to the Refraction Department of Vietnam National Eye Hospital. Inclusion criteria were high myopia (≤-6.00D with cycloplegic retinoscopy). Consecutive presenting patients recruited between January 2020 and August 2020 consented to participate. RESULTS: Participant age range was 12-47 years. Peripapillary atrophy was present in 70.2% of participants, most commonly atrophy of one-quarter of the disc (38.7%). Central retinal changes were present in 66.1% of participants, subclassified as tessellated fundus in 60.7%, diffuse chorioretinal atrophy in 4.2% and patchy chorioretinal atrophy in 1.2%. Peripheral retinal lesions were present in 43.5% of participants, consisting of white-without-pressure in 32.1%, lattice degeneration in 16.1%, snail track degeneration in 4.2% and microcystoid degeneration in 1.2%. Myopia ≤-8.00D and axial length ≥26.5 mm were associated with additional risk of posterior ocular complications. Furthermore, age ≥19 years increased risk of central myopic retinopathy and ≥10 years since initial myopia diagnosis increased the risk of peripapillary atrophy and central retinal changes. Other factors such as the age of onset of myopia and family myopia history did not appear to alter the risk of peripheral retina damage. CONCLUSIONS: Retinal disorders were common in Vietnamese people with high myopia. Within the current cohort with high myopia, myopia ≤-8.00D and axial length ≥26.5 mm were associated with a significant further elevation of risk.


Asunto(s)
Miopía Degenerativa , Miopía , Enfermedades de la Retina , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Transversales , Agudeza Visual , Prevalencia , Vietnam/epidemiología , Miopía/epidemiología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/epidemiología , Enfermedades de la Retina/etiología , Atrofia , Miopía Degenerativa/diagnóstico , Miopía Degenerativa/epidemiología
20.
Food Chem ; 404(Pt A): 134616, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36444043

RESUMEN

Shewanella baltica has a high spoilage ability to decompose nutrients in fish. To investigate the role of S. baltica in fish protein and flavour during spoilage, the texture, rheology, protein patterns and volatile compounds of golden pomfret inoculated with S. baltica during 10-day storage were tested. During storage, S. baltica reduced the hardness of fish sticks by 29.73-49.24 %. Compared to the control (G0': 20.27 ± 2.15 kPa), inoculated samples showed lower moduli (G0': 16.71 ± 0.82-17.50 ± 1.80 kPa). Their myosin heavy chains, myosin-binding protein C and actin were decomposed into smaller proteins, which was validated by the lower intensities of molecules with Mw 160-176 kDa. Furthermore, S. baltica generated volatile spoilage markers, including dimethyl sulfide, 2-methyl-butanal and 3-methyl-butanal. This study reveals the mechanism of fish texture and flavour changes induced by S. baltica, and provides insights into controlling bacterial spoilage of seafood.


Asunto(s)
Alimentos Marinos , Shewanella , Animales , Reología , Aromatizantes
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