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1.
Ann Occup Environ Med ; 36: e18, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144152

RESUMEN

Background: Disturbance of circadian rhythms caused by shift work has adverse effects on insulin resistance. Many previous studies have confirmed that shift work and insulin resistance are related using homeostasis model assessment-insulin resistance, one of the insulin resistance indicators. However, the triglycerides and glucose index (TyG index) has recently been studied as an insulin resistance indicator. The aim of this study is to investigate the association of shift work and TyG index, one of the indirect indicators of insulin resistance, using results of health checkups in one workplace. Methods: Based on medical examination data collected in February 2019, a total of 3,794 subjects from one chemical plant in Korea were selected for this study. Cut-off value of TyG index for predicting development of diabetes mellitus (DM) was 4.69. A multiple logistic regression analysis was performed after adjusting for age, employment period, obesity, abdominal obesity, smoking, drinking, physical activity, hypertension, stroke, heart disease. Results: As a result of logistic regression analysis, compared to day workers, odds ratio (OR) with a TyG index above cut-off value for predicting development of DM in shift workers was 1.220 after adjusting for age, employment period, obesity, abdominal obesity, smoking, drinking, physical activity, hypertension, stroke, heart disease (Model 1, OR: 1.276; 95% confidence interval [CI]: 1.099-1.482; Model 2, OR: 1.232; 95% CI: 1.055-1.438; Model 3, OR: 1.220, 95% CI: 1.030-1.444). Conclusions: There was a significant association between shift work and TyG index among male workers in a chemical plant. More research studies on the association between shift work and TyG index are needed in the future.

2.
EJNMMI Res ; 14(1): 59, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958796

RESUMEN

BACKGROUND: N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane (FP-CIT), the representative cocaine derivative used in dopamine transporter imaging, is a promising biomarker, as it reflects the severity of Parkinson's disease (PD). 123I- and 18F-labeled FP-CIT has been used for PD diagnosis. However, preclinical studies evaluating [18F]FP-CIT as a potential diagnostic biomarker are scarce. Among translational research advancements from bench to bedside, translating preclinical findings into clinical practice is one-directional. The aim of this study is to employ a circular approach, beginning back from the preclinical stage, progressing to the supplementation of [18F]FP-CIT, and subsequently returning to clinical application. We investigated the pharmacokinetic properties of [18F]FP-CIT and its efficacy for PD diagnosis using murine models. RESULTS: Biodistribution, metabolite and excretion analyses were performed in mice and PD models were induced in rats using 6-hydroxydopamine (6-OHDA). The targeting efficiency of [18F]FP-CIT for the dopamine receptor was assessed through animal PET/CT imaging. Subsequently, correlation analysis was conducted between animal PET/CT imaging results and immunohistochemistry (IHC) targeting tyrosine hydroxylase. Rapid circulation was confirmed after [18F]FP-CIT injection. [18F]FP-CIT reached the highest uptake of 23.50 ± 12.46%ID/g in the striatum 1 min after injection, and it was rapidly excreted within 60 min. The major metabolic organs of [18F]FP-CIT were confirmed to be the intestines, liver, and kidneys. Its uptake in the intestine was approximately 5% ID/g. The uptake in the liver gradually increased, with excretion beginning after reaching a maximum after 60 min. The kidneys exhibited rapid elimination after 10 min. In the excretion study, rapid elimination was verified, with 21.46 ± 9.53% of the compound excreted within a 6 h period. Additionally, the efficacy of [18F]FP-CIT PET was demonstrated in the PD model, with a high correlation with IHC for both the absolute value (R = 0.803, p = 0.0017) and the ratio value (R = 0.973, p = 0.0011). CONCLUSIONS: This study fills the gap regarding insufficient preclinical studies on [18F]FP-CIT, including its ADME, metabolites, and efficiency. The pharmacological results, including accurate diagnosis, rapid circulation, and [18F]FP-CIT excretion, provide complementary evidence that [18F]FP-CIT can be used safely and efficiently to diagnose PD in clinics, although it is already used in clinics.

3.
Curr Microbiol ; 81(9): 273, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39017960

RESUMEN

In pharmaceutical manufacturing, ensuring product safety involves the detection and identification of microorganisms with human pathogenic potential, including Burkholderia cepacia complex (BCC), Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Staphylococcus aureus, Clostridium sporogenes, Candida albicans, and Mycoplasma spp., some of which may be missed or not identified by traditional culture-dependent methods. In this study, we employed a metagenomic approach to detect these taxa, avoiding the limitations of conventional cultivation methods. We assessed the groundwater microbiome's taxonomic and functional features from samples collected at two locations in the spring and summer. All datasets comprised 436-557 genera with Proteobacteria, Bacteroidota, Firmicutes, Actinobacteria, and Cyanobacteria accounting for > 95% of microbial DNA sequences. The aforementioned species constituted less than 18.3% of relative abundance. Escherichia and Salmonella were mainly detected in Hot Springs, relative to Jefferson, while Clostridium and Pseudomonas were mainly found in Jefferson relative to Hot Springs. Multidrug resistance efflux pumps and BlaR1 family regulatory sensor-transducer disambiguation dominated in Hot Springs and in Jefferson. These initial results provide insight into the detection of specified microorganisms and could constitute a framework for the establishment of comprehensive metagenomic analysis for the microbiological evaluation of pharmaceutical-grade water and other non-sterile pharmaceutical products, ensuring public safety.


Asunto(s)
Bacterias , Agua Subterránea , Metagenómica , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Agua Subterránea/microbiología , Microbiota/genética , Preparaciones Farmacéuticas , Metagenoma , Microbiología del Agua
4.
Environ Health ; 23(1): 56, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858710

RESUMEN

BACKGROUND: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer. METHODS: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 µm, and fine particulate matter with a diameter < 2.5 µm-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality. RESULTS: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30). CONCLUSION: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Neoplasias Pulmonares , Mesotelioma Maligno , Humanos , Masculino , República de Corea/epidemiología , Neoplasias Pulmonares/mortalidad , Femenino , Anciano , Persona de Mediana Edad , Mesotelioma Maligno/mortalidad , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Estudios de Seguimiento , Contaminación del Aire/efectos adversos , Amianto/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Material Particulado/efectos adversos , Material Particulado/análisis , Anciano de 80 o más Años , Adulto , Mesotelioma/mortalidad , Mesotelioma/epidemiología
5.
J Nanobiotechnology ; 22(1): 83, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424578

RESUMEN

BACKGROUND: Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. Thus, we aimed to achieve consistent therapeutic effects by effectively depleting macrophages with uniform-sized liposomes. RESULTS: We developed four types of click chemistry-based liposome nanoplatforms that were uniformly sized and encapsulated with clodronate, for effective macrophage depletion, followed by conjugation with Man-N3 and radiolabeling. Functionalization with Man-N3 improves the specific targeting of M2 macrophages, and radioisotope labeling enables in vivo imaging of the liposome nanoplatforms. The functionalized liposome nanoplatforms are stable under physiological conditions. The difference in the biodistribution of the four liposome nanoplatforms in vivo were recorded using positron emission tomography imaging. Among the four platforms, the clodronate-encapsulated mannosylated liposome effectively depleted M2 macrophages in the normal liver and tumor microenvironment ex vivo compared to that by Clodrosome® and m-Clodrosome®. CONCLUSION: The newly-developed liposome nanoplatform, with finely tuned size control, high in vivo stability, and excellent ex vivo M2 macrophage targeting and depletion effects, is a promising macrophage-depleting agent.


Asunto(s)
Ácido Clodrónico , Liposomas , Masculino , Humanos , Liposomas/farmacología , Ácido Clodrónico/farmacología , Distribución Tisular , Macrófagos
6.
Mar Pollut Bull ; 199: 116041, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38237246

RESUMEN

In 2007, an unprecedented oil spill occurred in Taean, Korea. Although crude oil contains chemicals that could increase thyroid cancer risk, few studies have examined the long-term effects of oil exposure during clean-up and thyroid cancer incidence. We investigated the long-term thyroid cancer incidence among participants involved in clean-up work. 1798 participants engaged in at least two surveys since the baseline was tracked from 2008 to 2018. Participants reported the days they participated in oil clean-up works and cancer diagnoses. Cox proportional hazard models were used to estimate the hazard ratios between clean-up work duration and thyroid cancer. Over the 9-year follow-up, 30 thyroid cancer cases were diagnosed. A positive association was observed between clean-up duration and thyroid cancer risk. This effect was more pronounced among residents living <50 m from traffic roads. Our results indicate that crude oil clean-up work participation may increase the thyroid cancer risk.


Asunto(s)
Contaminación por Petróleo , Petróleo , Neoplasias de la Tiroides , Humanos , Estudios de Seguimiento , Accidentes , República de Corea/epidemiología
7.
Biomedicines ; 12(1)2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38255324

RESUMEN

The purpose of this study was to investigate the most appropriate methodological approach for the automatic measurement of rodent myocardial infarct polar map using histogram-based thresholding and unsupervised deep learning (DL)-based segmentation. A rat myocardial infarction model was induced by ligation of the left coronary artery. Positron emission tomography (PET) was performed 60 min after the administration of 18F-fluoro-deoxy-glucose (18F-FDG), and PET was performed after injecting 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone). Single photon emission computed tomography was performed 60 min after injection of 99mTc-hexakis-2-methoxyisobutylisonitrile and 201Tl. Delayed contrast-enhanced magnetic resonance imaging was performed after injecting Gd-DTPA-BMA. Three types of thresholding methods (naive thresholding, Otsu's algorithm, and multi-Gaussian mixture model (MGMM)) were used. DL segmentation methods were based on a convolution neural network and trained with constraints on feature similarity and spatial continuity of the response map extracted from images by the network. The relative infarct sizes measured by histology and estimated R2 for 18F-FDG were 0.8477, 0.7084, 0.8353, and 0.9024 for naïve thresholding, Otsu's algorithm, MGMM, and DL segmentation, respectively. DL-based method improved the accuracy of MI size assessment.

8.
Genes Genomics ; 46(3): 355-365, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37995039

RESUMEN

BACKGROUND: Many species of red algae belonging to the phylum Rhodophyta are consumed by humans as raw materials for nutrition and medicine. As the seaweed market grows, the importance of the laver species has increased. The classification of red algal species has changed significantly, and the accuracy of this classification has improved significantly in recent years. Here, we report the complete circular genomes of the chloroplasts (cp) and mitochondria (mt) of three laver species (Neoporphyra dentata, Neoporphyra seriata, and Neopyropia yezoensis). OBJECTIVE: This study aims to assemble, annotate, and characterize the organization of the organelle genomes of three laver species, conduct comparative genomic studies, and develop molecular markers based on SNPs. METHODS: We analyzed organelle genome structures, repeat sequences, sequence divergence, gene rearrangements, and phylogenetic relationships of three laver species. RESULTS: The chloroplast genomes of the three species contained an average of 212 protein-coding genes (PCGs), while the mitochondrial genomes contained an average of 25 PCGs. We reconstructed the phylogenetic trees based on both chloroplast and mitochondrial genomes using 201 and 23 PCGs (in cp and mt genomes, respectively) shared in the class Bangiophyceae (and five species of Florideophyceae class used as an outgroup). In addition, 12 species-specific molecular markers were developed for qRT-PCR analysis. CONCLUSIONS: This is the first report of Neoporphyra seriata complete organellar genomes. With the results, this study provides useful genetic information regarding taxonomic discrepancies, the reconstruction of phylogenetic trees, and the evolution of red algae. Moreover, the species-specific markers can be used as fast and easy methods to identify a target species.


Asunto(s)
Algas Comestibles , Porphyra , Rhodophyta , Algas Marinas , Humanos , Algas Marinas/genética , Filogenia , Rhodophyta/genética , Cloroplastos/genética
9.
Sci Total Environ ; 912: 168801, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38008335

RESUMEN

The Hebei Spirit oil spill accident occurred in December 2007, approximately 10 km off the coast of Taean, South Korea, a location notably close to residential areas. Crude oil substances have been detected in various environmental mediums since the accident, yet previous studies have primarily focused on the acute effects of oil exposure due to the short latency period of allergic diseases. Therefore, this study evaluated the long-term effects of oil spill exposure on allergic disorders. Our study included adult residents who had participated in the Health Effects Research on Hebei Spirit Oil Spill (HEROS) study up to five years post-incident, which was a prospective cohort to monitor the health status of Taean residents. We used two indicators to assess oil spill exposure, namely the distance from the initial contaminated coastline to each participant's residence and the number of days participants had engaged in oil clean-up work. Current symptoms such as asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and multimorbidity were considered allergic disorders. In the baseline survey, the prevalence of asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and allergic multimorbidity symptoms was associated with both exposure indicators; however, these associations were not observed in the two consecutive surveys. Significant longitudinal associations between oil spill exposure indicators and the four allergic disorders, as well as multimorbidity incidences, were observed during a five-year follow-up period. Our results suggest that oil spill exposure can affect acute and long-term allergic symptoms in residents near the accident site.


Asunto(s)
Asma , Conjuntivitis Alérgica , Dermatitis Atópica , Contaminación por Petróleo , Petróleo , Rinitis Alérgica , Adulto , Humanos , Contaminación por Petróleo/efectos adversos , Contaminación por Petróleo/análisis , Estudios Prospectivos , Incidencia , Prevalencia , República de Corea/epidemiología , Petróleo/análisis
10.
Mol Pharm ; 20(11): 5856-5864, 2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37851927

RESUMEN

The aim of this study is to evaluate a radioactive metal complex platform for brain tumor targeting. Herein, we introduce a new porphyrin derivative, 5,10,15,20-(tetra-N,N-dimethyl-4-aminophenyl)porphyrin (TDAP), in which four N,N-dimethyl-4-p-phenylenediamine (DMPD) moieties are conjugated to the porphyrin labeled with the radiometal 64Cu. DMPD affected the pharmacokinetics of porphyrin in terms of retention time in vivo and tumor-targeting ability relative to those of unmodified porphyrin. [64Cu]Cu-TDAP showed stronger enhancement than [64Cu]Cu-porphyrin in U87MG glioblastoma cells, especially in the cytoplasm and nucleus, indicating its tumor-targeting properties and potential use as a therapeutic agent. In the subcutaneous and orthotopic models of brain-tumor-bearing mice, [64Cu]Cu-TDAP was clearly visualized in the tumor site via positron emission tomography imaging and showed a tumor-to-brain ratio as high as 13. [64Cu]Cu-TDAP deserves attention as a new diagnostic agent that is suitable for the early diagnosis and treatment of brain tumors.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Porfirinas , Animales , Ratones , Línea Celular Tumoral , Radioisótopos de Cobre/farmacocinética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/diagnóstico por imagen , Glioblastoma/tratamiento farmacológico
11.
Diagnostics (Basel) ; 13(16)2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37627908

RESUMEN

BACKGROUND: This study compared the effects of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as 64Cu-chelating agents in newly developed prostate-specific membrane antigen (PSMA) target compounds, 64Cu-cudotadipep and 64Cu-cunotadipep, on pharmacokinetics. METHODS: The in vitro stability of the chelators was evaluated using human and mouse serum. In vitro PSMA-binding affinity and cell uptake were compared using human 22Rv1 cells. To evaluate specific PSMA-expressing tumor-targeting efficiency, micro-positron emission tomography (mcroPET)/computed tomography (CT) and biodistribution analysis were performed using PSMA+ PC3-PIP and PSMA- PC3-flu tumor xenografts. RESULTS: The serum stability of DOTA- or NOTA-conjugated 64Cu-cudotadipep and 64Cu-cunotadipep was >97%. The Ki value of the NOTA derivative, cunotadipep, in the in vitro affinity binding analysis was higher (2.17 ± 0.25 nM) than that of the DOTA derivative, cudotadipep (6.75 ± 0.42 nM). The cunotadipep exhibited a higher cellular uptake (6.02 ± 0.05%/1 × 106 cells) compared with the cudotadipep (2.93 ± 0.06%/1 × 106 cells). In the biodistribution analysis and microPET/CT imaging, the 64Cu-labeled NOTA derivative, 64Cu-cunotadipep, demonstrated a greater tumor uptake and lower liver uptake than the DOTA derivative. CONCLUSIONS: This study indicates that the PSMA-targeted 64Cu-cunotadipep can be applied in clinical practice owing to its high diagnostic power for prostate cancer.

12.
Ann Occup Environ Med ; 35: e12, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37455849

RESUMEN

Background: The purpose of this study is to investigate the relationship between job stress and impaired fasting glycemia (IFG) of male workers in a manufacturing industry. Methods: Data were collected from 5,886 male workers in a manufacturing industry who participated in the medical examination from June 19 to August 14, 2020 through self-reported questionnaires. The general characteristics of the subjects, shift work, high blood pressure, dyslipidemia, and job stress were included. Job stress was measured using the Korean Occupational Stress Scale (KOSS) consisting of 8 items and 43 questions. Multivariable logistic regression analysis was used to investigate the IFG association with job stress. Results: Among the various factors that can cause job stress, only high job demand was associated with a risk of IFG (odds ratio, 1.43; 95% confidence interval, 1.13-1.82) especially in non-shift worker. For all other factors, no statistically significant results were obtained. Conclusions: In this study of male workers engaged in the Korean steel manufacturing industry, the 'job demand' item among job stress of non-shift worker was related to IFG.

13.
Adv Sci (Weinh) ; 10(16): e2300462, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37066794

RESUMEN

Organic nanomaterials, as nanocarrier platforms, have tremendous potential for biomedical applications. The authors successfully prepared novel two-dimensional covalent organic nanosheets (CONs) that can be used as efficient in vivo bioimaging probes by condensing 1,3,5-triformylglucinol (Tp) and 2,7-diaminopyrene (Py) to produce TpPy covalent organic frameworks (COFs). TpPy COFs are then subjected to a liquid exfoliation process to obtain TpPy CONs (< 200 nm in size and < 1.7 nm in thickness). TpPy CONs disperse well in water to provide a stable, homogeneous colloidal suspension, which shows favorable photoluminescence properties. Cell viability tests using MDA-MB-231 and RAW 264.7 cells reveal that TpPy CONs are low in cytotoxicity. Confocal microscopy reveals clear fluorescent cell images after incubation with TpPy CONs for 24 h, without reduction in cell activity or cytosolic aggregation. To investigate the biological behavior of the TpPy CONs, the authors perform an in vivo fluorescence imaging study using MDA-MB-231 tumor-bearing mice. After intravenous injection of TpPy CONs disperse in phosphate-buffered saline (PBS), persistent and strong fluorescence signals are observed in the tumor region, with low background signals from normal tissues at 1, 3, 12, and 24 h after injection. Furthermore, these in vivo imaging results concurred with ex vivo biodistribution and histological results.


Asunto(s)
Nanoestructuras , Neoplasias , Animales , Ratones , Distribución Tisular , Imagen Molecular , Imagen Óptica
14.
Ann Occup Environ Med ; 35: e5, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37063597

RESUMEN

Background: Perfluoroalkyl substances (PFAS) are chemicals widely used in various products in everyday life. Due to its unique strong binding force, the half-life of PFAS is very long, so bioaccumulation and toxicity to the human body are long-standing concerns. In particular, effects on kidney function have recently emerged and there are no studies on the effect of PFAS on kidney function through epidemiological investigations in Korea. From 2018 to 2020, the Korean National Environmental Health Survey (KoNEHS) cycle 4, conducted an epidemiological investigation on the blood concentration of PFAS for the first time in Korea. Based on this data, the relationship between PFAS blood concentration and kidney function was analyzed for adolescents. Methods: We investigated 5 types of PFAS and their total blood concentration in 811 middle and high school students, living in Korea and included in KoNEHS cycle 4, and tried to find changes in kidney function in relation to PFAS concentration. After dividing the concentration of each of the 5 PFAS and the total concentration into quartiles, multivariable linear regression was performed to assess the correlation with kidney function. The bedside Schwartz equation was used as an indicator of kidney function. Results: As a result of multivariable linear regression, when observing a change in kidney function according to the increase in the concentration of each of the 5 PFAS and their total, a significant decrease in kidney function was confirmed in some or all quartiles. Conclusions: In this cross-sectional study of Korean adolescents based on KoNEHS data, a negative correlation between serum PFAS concentration and kidney function was found. A well-designed longitudinal study and continuous follow-up are necessary.

15.
Front Psychiatry ; 14: 1086370, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36846229

RESUMEN

Introduction: Traumatic events in early life have a deleterious effect on the development of normal brain developments, which may be a cause of various psychiatric disorders in adulthood. Most prior studies focused on molecular biological aspects, and research on functional changes in neural circuits is still limited. We aimed to elucidate the effect of early life stress on in vivo excitation-inhibition and serotonergic neurotransmission in the adulthood using non-invasive functional molecular imaging (positron emission tomography, PET). Methods: To compare the effect of stress intensity, early life stress animal models were divided into single trauma (MS) and double trauma groups (MRS). MS was derived from maternal separation, whereas MRS was derived from maternal separation and restraint stress after birth. And to evaluate the stress vulnerability on the sex, we used male and female rats. Results: The MRS group showed greater weight loss and more severe depressive/anxiety-like behaviors than the MS and control groups. Corticosterone levels in MRS showed a greater extent of decline than in the MS group; however, there was no significant difference in the change of T3 and T4 between MS and MRS. In the PET, the stress exposure groups showed lower brain uptake for GABAergic, glutamatergic, and serotonergic systems compared with the control group. The excitatory/inhibitory balance, which was derived by dividing glutamate brain uptake into GABAergic uptake, increased as stress intensity increased. Neuronal degeneration in the stress exposure groups was confirmed by immunohistochemistry. In the sex comparison, female showed the greater changes of body weight, corticosterone level, depressive/anxiety-like behavior, and neurotransmission systems than those in male. Conclusion: Taken together, we demonstrated that developmental stress induces dysfunction of neurotransmission in vivo, and that females are more vulnerable to stress than males.

16.
Biochem Biophys Res Commun ; 651: 107-113, 2023 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-36801611

RESUMEN

We have compared the similarity of the in vivo distribution of the prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging agents [18F]DCFPyL, [68Ga]galdotadipep, and [68Ga]PSMA-11. This study is designed for a further selection of a PSMA-targeted PET imaging agent for the therapeutic evaluation of [177Lu]ludotadipep, our previously developed prostate-specific membrane antigen (PSMA)-targeted prostate cancer therapeutic radiopharmaceutical. In vitro cell uptake was performed to evaluate the affinity to PSMA using PSMA + PC3-PIP, and PSMA- PC3-flu was used for the study. MicroPET/CT 60 min dynamic imaging and biodistribution were performed at 1, 2, and 4 h after injection. Autoradiography and immunohistochemistry were performed to evaluate the PSMA + tumor target efficiency. In the microPET/CT image, [68Ga]PSMA-11 showed the highest uptake in the kidney among all three compounds. [18F]DCFPyL and [68Ga]PSMA-11 showed similar patterns of in vivo biodistribution and high tumor targeting efficiency, similar to those of[68Ga]galdotadipep. All three agents showed high uptake in tumor tissue on autoradiography, and PSMA expression was confirmed by immunohistochemistry. Thus, [18F]DCFPyL or [68Ga]PSMA-11 can be used as a PET imaging agent to monitor [177Lu]ludotadipep therapy in prostate cancer patients.


Asunto(s)
Radioisótopos de Galio , Neoplasias de la Próstata , Humanos , Masculino , Detección Precoz del Cáncer , Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/patología , Radiofármacos , Distribución Tisular , Antígeno Prostático Específico/metabolismo
17.
Mol Pharm ; 20(1): 267-278, 2023 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-36542354

RESUMEN

Early diagnosis of radiation-induced pulmonary fibrosis (RIPF) in lung cancer patients after radiation therapy is important. A gastrin-releasing peptide receptor (GRPR) mediates the inflammation and fibrosis after irradiation in mice lungs. Previously, our group synthesized a GRPR-targeted positron emission tomography (PET) imaging probe, [64Cu]Cu-NODAGA-galacto-bombesin (BBN), an analogue peptide of GRP. In this study, we evaluated the usefulness of [64Cu]Cu-NODAGA-galacto-BBN for the early prediction of RIPF. We prepared RIPF mice and acquired PET/CT images of [18F]F-FDG and [64Cu]Cu-NODAGA-galacto-BBN at 0, 2, 5, and 11 weeks after irradiation (n = 3-10). We confirmed that [64Cu]Cu-NODAGA-galacto-BBN targets GRPR in irradiated RAW 264.7 cells. In addition, we examined whether [64Cu]Cu-NODAGA-galacto-BBN monitors the therapeutic efficacy in RIPF mice (n = 4). As a result, the lung uptake ratio (irradiated-to-normal) of [64Cu]Cu-NODAGA-galacto-BBN was the highest at 2 weeks, followed by its decrease at 5 and 11 weeks after irradiation, which matched with the expression of GRPR and was more accurately predicted than [18F]F-FDG. These uptake results were also confirmed by the cell uptake assay. Furthermore, [64Cu]Cu-NODAGA-galacto-BBN could monitor the therapeutic efficacy of pirfenidone in RIPF mice. We conclude that [64Cu]Cu-NODAGA-galacto-BBN is a novel PET imaging probe for the early prediction of RIPF-targeting GRPR expressed during the inflammatory response.


Asunto(s)
Fibrosis Pulmonar , Receptores de Bombesina , Animales , Ratones , Receptores de Bombesina/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/etiología , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones/métodos , Bombesina/metabolismo , Pulmón/diagnóstico por imagen , Pulmón/metabolismo , Línea Celular Tumoral
18.
Toxics ; 12(1)2023 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-38250976

RESUMEN

Malignant mesothelioma and asbestos-related lung cancer are typically associated with a poor prognosis. However, it has been observed that some patients with these cancers survive significantly longer than the average survival period. While many preliminary studies have investigated factors influencing patient survival, the specific impact of asbestos exposure has not been thoroughly explored. We followed up with 546 patients with malignant mesothelioma and 902 patients with asbestos-related lung cancer, all identified as asbestos victims between 2009 and 2021. In both malignant mesothelioma and asbestos-related lung cancer, patients with occupational asbestos exposure exhibited not only shorter median survival times but also lower 3- and 5-year survival rates compared to those with environmental exposure. Additionally, a longer duration of occupational exposure and closer proximity to the source of asbestos were linked to shorter survival times and lower survival rates. Among the patients with occupational asbestos exposure, the highest hazard ratios (HRs) were observed in those who worked in the production of asbestos-containing products across both cancer types. In contrast, significant HRs were only noted in mesothelioma patients who lived near asbestos industries, slate houses, and redevelopment areas, within the environmentally exposed group.

19.
Ann Occup Environ Med ; 34: e33, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36544884

RESUMEN

Background: Circadian rhythm disturbance caused by shift work has adverse effects on the metabolic homeostasis of the liver. Disruption of the metabolic homeostasis of the liver causes fat accumulation in the liver. The aim of this study was to investigate the correlation between shift work and non-alcoholic fatty liver disease (NAFLD) among male workers in the steel manufacturing industry of Korea. Methods: Based on medical examination data collected in June 2020, 2,511 male subjects from one steel manufacturing company in Korea were selected in total. NAFLD was evaluated using abdominal ultrasound, which was performed by two experienced radiologists. The multinomial logistic regression analysis was performed by adjusting for age, physical activity, smoking history, alcohol consumption, body mass index, waist circumference, blood pressure, blood glucose, lipidemia, liver function test, employment duration, and hepatotoxic materials exposure status. Results: Compared to daytime workers, the odds ratio (OR) of moderate-severe NAFLD in shift workers was 1.449 (95% confidence interval [CI], 1.028-2.043). Compared to daytime workers, the ORs of moderate-severe NAFLD were significantly higher for the group that engaged in total shift work for more than 20 years (OR, 2.285; 95% CI, 1.051-4.970), the group that was not allowed to sleep during night shift work (OR, 1.463; 95% CI, 1.030-2.078), and the group that consumed food during night shift work (OR, 1.580; 95% CI, 1.093-2.284). Conclusions: There was a correlation between shift work and moderate-severe NAFLD in male steel manufacturing workers. There will be a need for more research related to the correlation of shift work with steatohepatitis and cirrhosis in the future.

20.
Ann Occup Environ Med ; 34: e34, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36544886

RESUMEN

Background: This study aimed to investigate the association between lead exposure and serum gamma-glutamyl transpeptidase (γGT) levels as an oxidative stress marker in male steelworkers. Methods: Data were collected during the annual health examination of workers in 2020. A total of 1,654 steelworkers were selected, and the variables for adjustment included the workers' general characteristics, lifestyle, and occupational characteristics. The association between the blood lead level (BLL) and serum γGT level was investigated by multiple linear and logistic regression analyses. The BLL and serum γGT values that were transformed into natural logarithms were used in multiple linear regression analysis, and the tertile of BLL was used in logistic regression analysis. Results: The geometric mean of the participants' BLLs and serum γGT level was 1.36 µg/dL and 27.72 IU/L, respectively. Their BLLs differed depending on age, body mass index (BMI), smoking status, drinking status, shift work, and working period, while their serum γGT levels differed depending on age, BMI, smoking status, drinking status, physical activity, and working period. In multiple linear regression analysis, the difference in models 1, 2, and 3 was significant, obtaining 0.326, 0.176, and 0.172 (all: p < 0.001), respectively. In the multiple linear regression analysis stratified according to drinking status, BMI, and age, BLLs were positively associated with serum γGT levels. Regarding the logistic regression analysis, the odds ratio of the third BLL tertile in models 1, 2, and 3 (for having an elevated serum γGT level within the first tertile reference) was 2.74, 1.83, and 1.81, respectively. Conclusions: BLL was positively associated with serum γGT levels in male steelworkers even at low lead concentrations (< 5 µg/dL).

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