RESUMEN
BackgroundReports on the association between growth hormone deficiency (GHD) and cardiovascular risk factors in children are limited. We aim to investigate the effect of different doses of recombinant human growth hormone (rhGH) therapy on blood lipid and carotid intima-media thickness (cIMT) in Chinese GHD children.MethodsNinety children, including sixty isolated GHD children and thirty healthy children, were enrolled. GHD children were randomly divided into two groups (A and B) according to the rhGH dose given: group A received 0.23 mg/kg/week and group B received 0.35 mg/kg/week for 12 months. The TC, TG, LDL-C, HDL-C, and cIMT at baseline and after treatment were measured.ResultsThe height, weight, and height velocity improved significantly over 12 months of rhGH therapy in all GHD children. At baseline, GHD children in both the treatment groups showed significantly higher total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), cIMT, and lower high-density lipoprotein-cholesterol (HDL-C) than healthy children (all P≤0.033). After the 12-month rhGH therapy, a significant decrease in the TC, TG, LDL-C, and cIMT, as well as a significant increase in the HDL-C (P≤0.046), was observed in the GHD children, with change in the group B being even more marked.ConclusionsThe RhGH replacement therapy in GHD children can improve both the blood lipid profile and carotid intima-media thickness, with higher-dose rhGH therapy showing superior effects.
Asunto(s)
Grosor Intima-Media Carotídeo , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Lípidos/sangre , Proteínas Recombinantes/uso terapéutico , Estatura , Peso Corporal , Huesos , Sistema Cardiovascular , Arterias Carótidas/patología , Estudios de Casos y Controles , Niño , Preescolar , China , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Metabolismo de los Lípidos , Masculino , Estudios Prospectivos , Factores de Riesgo , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
Aims: Whether pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma agonist, increases the risk of developing bladder cancer has been debated for several years. The aim of this study was to investigate the in vitro effects of PIO on normal urothelial transitional epithelium (NUTE) cells and bladder cancer (J82) cells to further evaluate the risk. Methods: NUTE cells were obtained from Sprague-Dawley rats. NUTE and J82 cells were treated with different concentrations of PIO for various time periods. Cell proliferation was tested by the MTT assay. Cell apoptosis was evaluated by flow cytometry. The expressions of p53, cyclin D1, Bcl-2, and Bax were determined by qRT-PCR and western blots. Results: After 24 hours, the treatment of NUTE cells with 10 µmol/L PIO led to morphological changes, without changes in J82 cells. Moreover, PIO inhibited the proliferation and induced apoptosis of NUTE cells, but not J82 cells, in a time- and dose-dependent manner. However, PIO did not alter the growth of cells from other tissues. In addition, treatment with PIO for up to 72 hours did not result in changes in the expressions of p53, cyclin D1, Bcl-2, and Bax in NUTE cells and J82 cells. Interestingly, PIO significantly downregulated the protein levels of p53 and cyclin D1 in J82 cells, but not NUTE cells after more than 192 hours of treatment. Conclusions: PIO did not promote malignant alterations of NUTE cells or stimulate proliferation of J82 cells. PIO decreased the expression of p53 and cyclin D1 in J82 cells after long-term culture, which suggested that PIO may be helpful for diabetic patients with bladder cancer.
Asunto(s)
Complicaciones de la Diabetes/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Tiazolidinedionas/administración & dosificación , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclina D1/genética , Complicaciones de la Diabetes/genética , Complicaciones de la Diabetes/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , PPAR gamma/agonistas , Pioglitazona , Proteínas Proto-Oncogénicas c-bcl-2/genética , Ratas , Factores de Riesgo , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Urotelio/efectos de los fármacos , Urotelio/patologíaRESUMEN
Celastrol, a triterpenoid isolated from stem (caulis) of Celastrus orbiculatus Thunb. (Celastraceae), has been known to have various pharmacological effects, including anti-inflammatory, anticancer, and antioxidant activities. However, the mechanism of the intestinal absorption of celastrol is unknown. The aim of this study was to investigate the intestinal absorption of celastrol using the Caco-2 cell transwell model. First, the bidirectional transport of celastrol in Caco-2 cell monolayers was observed. Then, the effects of time, concentration, temperature, paracellular pathway, and efflux transport inhibition on the transport of celastrol across the Caco-2 cell monolayers were investigated. The P-glycoprotein inhibitor verapamil and cyclosporin A, the multidrug resistance protein 2 inhibitor MK571, and the breast cancer resistance protein inhibitor reserpine were used. Additionally, the effects of celastrol on the activity of P-glycoprotein were evaluated using the rhodamine 123 uptake assay. In this study, we found that the intestinal transport of celastrol was a time- and concentration-dependent active transport. The paracellular pathway was not involved in the transport of celastrol, and the efflux of celastrol was energy dependent. The results indicated that celastrol is a substrate of P-glycoprotein but not multidrug resistance protein 2 or the breast cancer resistance protein. In addition, celastrol could not affect the uptake of rhodamine 123 in Caco-2 cells, which indicated that celastrol could not inhibit or induce the activity of P-glycoprotein.
Asunto(s)
Absorción Intestinal , Triterpenos/farmacocinética , Antiinflamatorios no Esteroideos/farmacocinética , Antineoplásicos Fitogénicos/farmacocinética , Transporte Biológico , Células CACO-2 , Proteínas Portadoras/metabolismo , Celastrus/química , Humanos , Mucosa Intestinal/metabolismo , Triterpenos Pentacíclicos , Rodamina 123/metabolismo , Temperatura , Factores de TiempoRESUMEN
Background: Age-related Macular Degeneration (AMD) poses a growing global health concern as the leading cause of central vision loss in elderly people. Objection: This study focuses on unraveling the intricate involvement of Natural Killer (NK) cells in AMD, shedding light on their immune responses and cytokine regulatory roles. Methods: Transcriptomic data from the Gene Expression Omnibus database were utilized, employing single-cell RNA-seq analysis. High-dimensional weighted gene co-expression network analysis (hdWGCNA) and single-cell regulatory network inference and clustering (SCENIC) analysis were applied to reveal the regulatory mechanisms of NK cells in early-stage AMD patients. Machine learning models, such as random forests and decision trees, were employed to screen hub genes and key transcription factors (TFs) associated with AMD. Results: Distinct cell clusters were identified in the present study, especially the T/NK cluster, with a notable increase in NK cell abundance observed in AMD. Cell-cell communication analyses revealed altered interactions, particularly in NK cells, indicating their potential role in AMD pathogenesis. HdWGCNA highlighted the turquoise module, enriched in inflammation-related pathways, as significantly associated with AMD in NK cells. The SCENIC analysis identified key TFs in NK cell regulatory networks. The integration of hub genes and TFs identified CREM, FOXP1, IRF1, NFKB2, and USF2 as potential predictors for AMD through machine learning. Conclusion: This comprehensive approach enhances our understanding of NK cell dynamics, signaling alterations, and potential predictive models for AMD. The identified TFs provide new avenues for molecular interventions and highlight the intricate relationship between NK cells and AMD pathogenesis. Overall, this study contributes valuable insights for advancing our understanding and management of AMD.
RESUMEN
As an emerging contaminant in soil, the impact of microplastics (MPs) on the environmental behavior of other organic pollutants remains uncertain, potentially threatening the sustainability of agricultural production. In this study, the impact of two kinds of MPs on the environmental behaviors of herbicide atrazine in soil-plant system was investigated. The results showed that MPs significantly reduced the half-life 17.69 â¼ 21.86 days of atrazine in the soil, compared to the control group. Meanwhile, the introduction of MPs substantially increased atrazine adsorption. Additionally, MPs substantially enriched the diversity and functionality of soil microbiome, and the soil metabolic activity was stimulated. Regarding the crop growth, the accumulation of atrazine in maize were significantly decreased by approximately 48.4-78.5 % after exposure to MPs. In conclusion, this study reveals the impact of MPs on atrazine's environmental behaviors in soil and highlights their less effect on maize growth, providing valuable insights for managing MPs contamination in sustainable agriculture.
Asunto(s)
Atrazina , Herbicidas , Contaminantes del Suelo , Atrazina/metabolismo , Microplásticos/metabolismo , Suelo , Plásticos/metabolismo , Adsorción , Bioacumulación , Contaminantes del Suelo/metabolismo , Zea mays/metabolismoRESUMEN
Although age-related macular degeneration (AMD) is the leading cause of legal blindness, the treatment methods for AMD are limited. The aim of the present study was to examine the association between oral ß-blockers (BBs) and the risk of developing AMD among hypertensive patients. For this purpose, a total of 3,311 hypertensive patients from the National Health and Nutrition Examination Survey were included in the study. The use of BBs and treatment duration data were collected using a self-reported questionnaire. AMD was diagnosed by gradable retinal images. Multivariate-adjusted survey-weighted univariate logistic regression was used to confirm the association between the use of BBs and the risk of developing AMD. The results revealed that the use of BBs exerted a beneficial effect (odds ratio (OR), 0.34; 95% confidence interval (95% CI, 0.13-0.92; P=0.04) in late-stage AMD in the multivariate adjusted model. When the BBs were classified into non-selective BBs and selective BBs, the protective effect in late-stage AMD was still observed in the non-selective BBs (OR, 0.20; 95% CI, 0.07-0.61; P<0.001). After accounting for treatment duration, long-term treatment with BBs (>6 years) was also found to reduce the risk of late-stage AMD (OR, 0.13; 95% CI, 0.03-0.63; P=0.01). In late-stage AMD, the long-term use of BBs was beneficial for geographic atrophy (OR, 0.07; 95% CI, 0.02-0.28; P<0.001). On the whole, the present study demonstrates that the use of non-selective BBs exerted a beneficial effect against the risk of late-stage AMD among hypertensive patients. Long-term treatment with BBs was also associated with lower risk of developing AMD. These findings may provide novel strategies for the management and treatment of AMD.
RESUMEN
AIMS: To investigate the association of diabetes mellitus with prostate cancer (PCa) grade and prostate-specific antigen (PSA) in Chinese biopsy population. METHODS: We retrospectively evaluated data from 2032 patients who underwent prostate biopsies from 2010 to 2016 at our hospital. All diabetes cases were divided into sub-groups according to HbA1c (<6.5%, 6.5%-7.49% and ≥7.5%) and diabetes duration (0-5â¯years, 6-10â¯years and >10â¯years). RESULTS: Among 2032 men, 467 (23.0%) were diabetic and 674 (33.2%) were diagnosed with PCa. Diabetes increased the overall risk of PCa (ORâ¯=â¯1.51, 95%CI: 1.12-2.05, Pâ¯=â¯0.007), especially high-grade PCa (ORâ¯=â¯2.30, 95%CI: 1.47-3.61, Pâ¯<â¯0.001), but was not associated with low- or intermediate-grade PCa. High-grade PCa risk was markedly increased in patients with increased diabetic duration and HbA1c. Moreover, diabetics had a 22.8% lower geometric mean PSA level than non-diabetics (6.42 vs. 8.31â¯ng/mL, Pâ¯<â¯0.001) and the difference increased with diabetic duration. CONCLUSIONS: Diabetes was associated with a higher risk of PCa detection, especially high-grade disease in Chinese biopsy patients. We speculate that low PSA levels in diabetics might delay and/or interfere with PCa detection, eventually leading to higher degree PCa on diagnosis.
Asunto(s)
Complicaciones de la Diabetes/fisiopatología , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/etiología , Anciano , Pueblo Asiatico , Biopsia , Humanos , Masculino , Clasificación del Tumor , Neoplasias de la Próstata/patología , Estudios RetrospectivosRESUMEN
AIMS: To explore the association of type 2 diabetes mellitus (T2DM) with hepatocellular carcinoma (HCC) and alpha fetoprotein (AFP). METHODS: 750 patients with T2DM (T2DM group), 800 healthy people (control group) and 501 patients newly diagnosed with HCC were recruited from 2010 to 2016. The HCC patients were further divided into a HCC with T2DM (HCC+DM) group and a HCC without diabetes mellitus (HCC+NDM) group. RESULTS: The T2DM group had a 12.61% lower geometric mean AFP level than the healthy control group (2.08 vs. 2.38⯵g/L, Pâ¯<â¯0.001). Of 501 HCC patients, 230 (45.91%) had T2DM. When compared to the HCC+NDM group, the HCC+DM group had a higher negative rate of AFP (55.22% vs. 37.26%, Pâ¯<â¯0.001), worse liver function (Pâ¯=â¯0.011) and a 64.87% lower geometric mean AFP level (25.71 vs. 73.18⯵g/L, Pâ¯<â¯0.001). T2DM was significantly associated with the risk of high-grade (grade 3 and 4) HCC (ORâ¯=â¯2.02, 95% CI 1.18-3.44, Pâ¯=â¯0.010). CONCLUSIONS: T2DM was associated with lower AFP level, worse liver function and higher risk of high-grade HCC. We speculated that low AFP levels in diabetics might delay and interfere with HCC diagnosis, leading to higher degree of malignant HCC.