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OBJECTIVE: The remodelling of gut mycobiome (ie, fungi) during pregnancy and its potential influence on host metabolism and pregnancy health remains largely unexplored. Here, we aim to examine the characteristics of gut fungi in pregnant women, and reveal the associations between gut mycobiome, host metabolome and pregnancy health. DESIGN: Based on a prospective birth cohort in central China (2017 to 2020): Tongji-Huaxi-Shuangliu Birth Cohort, we included 4800 participants who had available ITS2 sequencing data, dietary information and clinical records during their pregnancy. Additionally, we established a subcohort of 1059 participants, which included 514 women who gave birth to preterm, low birthweight or macrosomia infants, as well as 545 randomly selected controls. In this subcohort, a total of 750, 748 and 709 participants had ITS2 sequencing data, 16S sequencing data and serum metabolome data available, respectively, across all trimesters. RESULTS: The composition of gut fungi changes dramatically from early to late pregnancy, exhibiting a greater degree of variability and individuality compared with changes observed in gut bacteria. The multiomics data provide a landscape of the networks among gut mycobiome, biological functionality, serum metabolites and pregnancy health, pinpointing the link between Mucor and adverse pregnancy outcomes. The prepregnancy overweight status is a key factor influencing both gut mycobiome compositional alteration and the pattern of metabolic remodelling during pregnancy. CONCLUSION: This study provides a landscape of gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health, which lays the foundation of the future gut mycobiome investigation for healthy pregnancy.
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Microbioma Gastrointestinal , Micobioma , Humanos , Femenino , Embarazo , Microbioma Gastrointestinal/fisiología , Adulto , Estudios Prospectivos , China , Metaboloma , Hongos/aislamiento & purificación , Recién NacidoRESUMEN
BACKGROUND: Liver plays an important role in maintaining glucose homeostasis. We aimed to examine the associations of liver enzymes and hepatic steatosis index (HSI, a reliable biomarker for non-alcoholic fatty liver disease) in early pregnancy with subsequent GDM risk, as well as the potential mediation effects of lipid metabolites on the association between HSI and GDM. METHODS: In a birth cohort, liver enzymes were measured in early pregnancy (6-15 gestational weeks, mean 10) among 6,860 Chinese women. Multivariable logistic regression was performed to examine the association between liver biomarkers and risk of GDM. Pearson partial correlation and least absolute shrinkage and selection operator (LASSO) regression were conducted to identify lipid metabolites that were significantly associated with HSI in a subset of 948 women. Mediation analyses were performed to estimate the mediating roles of lipid metabolites on the association of HSI with GDM. RESULTS: Liver enzymes and HSI were associated with higher risks of GDM after adjustment for potential confounders, with ORs ranging from 1.42 to 2.24 for extreme-quartile comparisons (false discovery rate-adjusted P-trend ≤0.005). On the natural log scale, each SD increment of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and HSI was associated with a 1.15-fold (95% CI: 1.05, 1.26), 1.10-fold (1.01, 1.20), 1.21-fold (1.10, 1.32), 1.15-fold (1.04, 1.27), and 1.33-fold (1.18, 1.51) increased risk of GDM, respectively. Pearson partial correlation and LASSO regression identified 15 specific lipid metabolites in relation to HSI. Up to 52.6% of the association between HSI and GDM risk was attributed to the indirect effect of the HSI-related lipid score composed of lipid metabolites predominantly from phospholipids (e.g., lysophosphatidylcholine and ceramides) and triacylglycerol. CONCLUSIONS: Elevated liver enzymes and HSI in early pregnancy, even within a normal range, were associated with higher risks of GDM among Chinese pregnant women. The association of HSI with GDM was largely mediated by altered lipid metabolism.
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Diabetes Gestacional , Embarazo , Femenino , Humanos , Diabetes Gestacional/epidemiología , Diabetes Gestacional/etiología , Estudios Prospectivos , Mujeres Embarazadas , Factores de Riesgo , Pueblos del Este de Asia , Hígado , Biomarcadores , LípidosRESUMEN
OBJECTIVE: To examine the association of a combined healthy lifestyle in early pregnancy with gestational diabetes mellitus (GDM) risk. DESIGN, SETTING AND POPULATION: A Chinese prospective cohort study with 6980 pregnant women. METHODS: Individual modifiable lifestyle factors were assessed in early pregnancy and a combined lifestyle score was derived from the sum of the lifestyle factors, with a higher score indicating a healthier lifestyle. The association of a combined healthy lifestyle with GDM risk was examined. MAIN OUTCOME MEASURES: Gestational diabetes mellitus was diagnosed in middle pregnancy according to the International Association of Diabetes and Pregnancy Study Group criteria or diagnoses in medical records. RESULTS: Overall, 501 (7.2%) pregnant women were diagnosed with GDM. Being physically active (total energy expenditure in upper three quintiles, i.e. ≥100.1 metabolic equivalent of task [MET]-hours/week; odds ratio [OR] 0.76, 95% confidence interval [CI] 0.63-0.92), healthy diet (total intake of vegetables and fruits ≥5 times/day; OR 0.74, 95% CI 0.59-0.94), sufficient sleep (night-time sleep duration ≥7 hours/night; OR 0.66, 95% CI 0.48-0.90) and healthy weight (early-pregnancy BMI <24.0 kg/m2 ; OR 0.57, 95% CI 0.46-0.71) were associated with lower GDM risk. The GDM risk decreased linearly across the combined lifestyle score (Ptrend <0.001): women with 2, 3 and 4 lifestyle factors compared with those with 0-1 factor had 38% (OR 0.62, 95% CI 0.46-0.84), 57% (OR 0.43, 95% CI 0.31-0.58) and 66% (OR 0.34, 95% CI 0.22-0.52) lower risks of GDM, respectively. CONCLUSION: A healthy lifestyle in early pregnancy was associated with a substantially lower GDM risk.
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Diabetes Gestacional , Embarazo , Femenino , Humanos , Diabetes Gestacional/epidemiología , Diabetes Gestacional/etiología , Estudios Prospectivos , Estilo de Vida Saludable , Estilo de Vida , Factores de RiesgoRESUMEN
Advanced prostate cancer often develops into bone metastasis, which is characterized by aberrant bone formation with chronic pain and lower chances of survival. No treatment exists as yet for osteoblastic bone metastasis in prostate cancer. The indolamine melatonin (N-acetyl-5-methoxytryptamine) is a major regulator of the circadian rhythm. Melatonin has shown antiproliferative and antimetastatic activities but has not yet been shown to be active in osteoblastic bone lesions of prostate cancer. Our study investigations reveal that melatonin concentration-dependently decreases the migratory and invasive abilities of two osteoblastic prostate cancer cell lines by inhibiting FAK, c-Src, and NF-κB transcriptional activity via the melatonin MT1 receptor, which effectively inhibits integrin α2 ß1 expression. Melatonin therapy appears to offer therapeutic possibilities for reducing osteoblastic bone lesions in prostate cancer.
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Melatonina , Neoplasias de la Próstata , Línea Celular Tumoral , Humanos , Integrina alfa2beta1/uso terapéutico , Masculino , Melatonina/farmacología , Melatonina/uso terapéutico , FN-kappa B/metabolismo , Neoplasias de la Próstata/metabolismoRESUMEN
Prostate cancer is a major cause of cancer-related mortality in men in developed countries. The compound, 4-acetylantroquinonol B (4AAQB), is isolated from Antrodia cinnamomea (commonly known as Niu-Chang-Chih), which has been shown to inhibit cancer growth. However, the anticancer activity of 4AAQB has not previously been examined in prostate cancer. This study aimed to investigate the effect of 4AAQB on cancer and angiogenesis, as well as to explore its mechanism of action. Human prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) were used in cell viability, cell migration, and cell cycle functional assays to evaluate the anticancer and antiangiogenic efficacy of 4AAQB in vitro. The effects of 4AAQB in vivo were determined using xenograft and angiogenesis models. The signaling events downstream of 4AAQB were also examined. The 4AAQB compound inhibited PC3 cell growth and migration, and reduced in vivo cancer growth, as shown in a subcutaneous xenograft model. Furthermore, 4AAQB inhibited HUVEC migration, tube formation, and aortic ring sprouting; it also reduced neovascularization in a Matrigel implant angiogenesis assay in vivo. The 4AAQB compound also decreased metastasis in the PC3 prostate cancer model in vivo. Serum or vascular endothelial growth factor (VEGF)-induced VEGF receptor 2 (VEGFR2), phosphoinositide 3-kinase (PI3K)/Ak strain transforming (Akt), and extracellular signal-regulated kinase ½ (ERK ½) phosphorylation were attenuated by 4AAQB in both PC3 and HUVEC. In conclusion, 4AAQB is a potential candidate for prostate cancer therapy.
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4-Butirolactona/análogos & derivados , Inhibidores de la Angiogénesis/administración & dosificación , Ciclohexanonas/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , 4-Butirolactona/administración & dosificación , 4-Butirolactona/farmacología , Inhibidores de la Angiogénesis/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ciclohexanonas/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Células PC-3 , Fosfatidilinositol 3-Quinasa/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP-13) expression are higher in prostate cancer patients than in healthy cancer-free individuals. Mechanistic investigations revealed that melatonin inhibits MMP-13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c-Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP-13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations.
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Metaloproteinasa 13 de la Matriz/metabolismo , Melatonina/farmacología , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/patología , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Humanos , Masculino , Ratones SCID , Modelos Biológicos , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteínas Proto-Oncogénicas c-jun/metabolismo , Receptores de Melatonina/metabolismo , Fosfolipasas de Tipo C/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
PURPOSE: We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality. METHODS: We searched PubMed and EMBASE through January 2019 for prospective studies that reported the association of vitamin K (assessed by dietary intake or circulating concentration) with CVD events [including total CVD, CVD mortality, total coronary heart disease (CHD), fatal CHD, nonfatal myocardial infarction (MI), and stroke] and all-cause mortality. Multivariable-adjusted hazard ratios (HRs) comparing top versus bottom tertiles of vitamin K were combined using random-effects meta-analysis. RESULTS: Twenty-one articles were included with 222,592 participants. A significant association was found between dietary phylloquinone and total CHD (pooled HR 0.92; 95% CI 0.84, 0.99; I2 = 0%; four studies), as well as menaquinone and total CHD (0.70; 95% CI 0.53, 0.93; I2 = 32.1%; two studies). No significant association was observed between dietary vitamin K and all-cause mortality, CVD mortality, or stroke. Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI 1.48, 2.28; I2 = 16.8%; five studies) and CVD mortality (1.96; 95% CI 1.47, 2.61; I2 = 0%; two studies). No significant association was observed between circulating total osteocalcin and all-cause mortality or total CVD. CONCLUSIONS: Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality. However, causal relations cannot be established because of limited number of available studies, and larger prospective studies and randomized clinical trials are needed to validate the findings.
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Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Muerte , Dieta/métodos , Vitamina K/farmacología , Enfermedades Cardiovasculares/dietoterapia , Humanos , Factores de Riesgo , Vitamina K/administración & dosificaciónRESUMEN
BACKGROUND: Melanoma is an aggressive skin cancer and a predominant cause of skin cancer-related deaths. A previous study has demonstrated the ability of butein to inhibit tumor proliferation and invasion. However, the anti-metastatic mechanisms and in vivo effects of butein have not been fully elucidated. METHODS: MTT cell viability assays were used to evaluate the antitumor effects of butein in vitro. Cytotoxic effects of butein were measured by lactate dehydrogenase assay. Anti-migratory effects of butein were evaluated by two-dimensional scratch and transwell migration assays. Signaling transduction and VEGF-releasing assays were measured by Western blotting and ELISA. We also conducted an experimental analysis of the metastatic potential of tumor cells injected into the tail vein of C57BL/6 mice. RESULTS: We first demonstrated the effect of butein on cell viability at non-cytotoxic concentrations (1, 3, and 10 µM). In vitro, butein was found to inhibit the migration of B16F10 cells in a concentration-dependent manner using transwell and scratch assays. Butein had a dose-dependent effect on focal adhesion kinase, Akt, and ERK phosphorylation in B16F10 cells. Butein efficiently inhibited the mTOR/p70S6K translational inhibition machinery and decreased the production of VEGF in B16F10 cells. Furthermore, the in vivo antitumor effects of butein were demonstrated using a pulmonary metastasis model. CONCLUSION: The results of the present study indicate the potential utility of butein in the treatment of melanoma.
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Chalconas/administración & dosificación , Melanoma Experimental/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Melanoma Experimental/fisiopatología , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia , Transducción de Señal/efectos de los fármacos , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/fisiopatología , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
OBJECTIVE: To analyze the association between patients with varicocele and varicose veins in Taiwan. METHODS: Between 2001 and 2010, comprehensive data were analyzed on the characteristics of patients with varicocele and varicose veins in Taiwan through a retrospective, nationwide, population-based study. Data were obtained from the Taiwan National Health Insurance Research Database. A total of 2727 cases with varicose veins and 10 908 randomly selected controls were included in this study. Conditional logistic regression analyses were used to examine the association between varicose veins and varicocele. RESULTS: The prevalence of varicocele was 1.3% and 0.3% for cases (with varicose veins) and controls (without varicose vein), respectively (P < 0.001). Conditional logistic regression analysis showed that the odds ratio of being previously diagnosed with varicose veins for cases was 4.71 (95% confidence interval 2.87-7.89) when compared with controls after adjusting for age, diabetes, heart disease, chronic obstructive pulmonary disease, liver and kidney disease, and edema. Furthermore, the odds ratio was 5.96 (95% confidence interval 2.90-12.24), 4.76 (95% confidence interval 1.68-13.48) and 1.69 (95% confidence interval 0.30-9.55) in patients aged <50 years, 51-65 years and >65 years, respectively. In addition, the prevalence of male infertility was 15.1% for patients with varicocele and varicose veins, and 14.5% for patients with varicocele only, but no significant difference was observed. CONCLUSION: Our findings suggest an association between both varicocele and varicose veins. In addition, this association is higher in patients aged younger than 50 years. Evaluation of male patients with varicose veins for varicocele should be recommended.
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Infertilidad Masculina/epidemiología , Varicocele/epidemiología , Várices/epidemiología , Factores de Edad , Anciano , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Estudios Retrospectivos , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a major contributor to the world's cancer burden. Understanding the HCC incidence rate in Taiwan is thus an interesting avenue of research. METHODS: From an NHI database, those patients who had been newly diagnosed with HCC and who had been listed on a registry in a catastrophic illness dataset during the years 2013-2021 were enrolled in this study. Antineoplastic agent usage and comorbidities were also studied. RESULTS: The incidence rate of HCC decreased from 57.77 to 44.95 in 100,000 from 2013 to 2021. The average age of patients with HCC increased from 65.54 years old with a CCI score of 4.98 in 2013 to 67.92 years old with a CCI score of 5.49 in 2021. Among these HCC patients, the patients under antineoplastic agent treatment decreased from 53.47% to 31.41% from 2013 to 2021. The presence of comorbidities in HCC patients was about 55.77-83.01% with mild liver disease and 29.93-37.30% with diabetes (without complications) in the period 2013-2021. CONCLUSIONS: The incidence rate of HCC slightly decreased in Taiwan. Due to antineoplastic agent usage decreasing over time, these results may indicate that more early-stage HCC patients detected in recent years were mainly treated with surgeries.
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Long non-coding RNAs (lncRNAs) are pivotal controllers of gene expression through epigenetic mechanisms, Methylation, a prominent area of study in epigenetics, significantly impacts cellular processes. Various RNA base methylations, including m6A, m5C, m1A, and 2'-O-methylation, profoundly influence lncRNA folding, interactions, and stability, thereby shaping their functionality. LncRNAs and methylation significantly contribute to tumor development, especially in lung cancer. Their roles encompass cell differentiation, proliferation, the generation of cancer stem cells, and modulation of immune responses. Recent studies have suggested that dysregulation of lncRNA methylation can contribute to lung cancer development. Furthermore, methylation modifications of lncRNAs hold potential for clinical application in lung cancer. Dysregulated lncRNA methylation can promote lung cancer progression and may offer insights into potential biomarker or therapeutic target. This review summarizes the current knowledge of lncRNA methylation in lung cancer and its implications for RNA epigenetics and pulmonary diseases.
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Epigénesis Genética , Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Animales , Regulación Neoplásica de la Expresión Génica , Metilación , Enfermedades Pulmonares/genética , Metilación de ADN/genéticaRESUMEN
SCOPE: Among patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association. METHODS AND RESULTS: This study includes 5405 participants with T2D who provided at least one 24-h dietary recall from the UK Biobank study. In the fully adjusted models, a 10% increase in the proportion of UPFs is associated with higher hazards of overall CVD (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.04, 1.15), coronary heart disease (HR: 1.10; 95% CI: 1.04, 1.16), heart failure (HR: 1.14; 95% CI: 1.05, 1.25), but not stroke (HR: 1.01; 95% CI: 0.90, 1.12). Cystatin C, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A, C-reactive protein, and body mass index collectively explain 26.9% (12.8%, 48.5%) of the association between UPF intake and the risk of overall CVD. CONCLUSION: Higher UPF intakes are associated with increased hazards of CVD among individuals with T2D, and the association is partly mediated through worsening biomarkers of renal function, lipid metabolism, inflammation, and body weight.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Alimentos Procesados , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Dieta , Manipulación de Alimentos , Factores de Riesgo , Biobanco del Reino Unido , Reino Unido/epidemiologíaRESUMEN
Recognizing the risk factors for dyslipidemia during pregnancy is crucial for safeguarding the health of both the mothers and the offspring. Growing evidence emerged and suggested links between environmental factors, including metals, and alteration in lipid levels or dyslipidemia in general populations. However, knowledge of the associations during pregnancy remains extremely lacking. Herein, we aimed to explore whether elevated metal exposure constitutes a risk factor for dyslipidemia in pregnant women. Based on the Tongji-Shuangliu Birth Cohort (TSBC), a total of 663 pregnant women were recruited and their urinary levels of 17 metals and blood lipid biomarkers in early pregnancy were measured, namely triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). The multivariable linear regression models revealed that exposure to selected metals during early pregnancy was significantly associated with some important biomarkers. In particular, after natural log-transformed for the levels of lipid biomarkers and metals, copper (Cu) exposure was positively associated with HDL-C (ß = 0.024, 95% CI: 0.001, 0.046), while zinc (Zn) was associated with TG (ß = 0.062, 95% CI: 0.013, 0.110) and selenium with TC (ß = 0.028, 95% CI: 0.004, 0.054). Exposure to rubidium (Rb) was positively associated with multiple lipid biomarkers, including HDL-C (ß = 0.020, 95% CI: 0.002, 0.037) and LDL-C (ß = 0.022, 95% CI: 0.001, 0.042). Mixture exposure analysis further identified significant associations between Cu and HDL-C, Zn and TG, Rb and HDL-C, when multiple metal exposures were considered in the Bayesian kernel machine regression model simultaneously. Our findings showed that exposure to several metals during early pregnancy was associated with an increased prevalence of blood lipid abnormalities in pregnant women. These findings underscore the potential impact of metal combinations on lipid metabolism and increase our understanding of the risk factors associated with abnormal lipid metabolism during pregnancy.
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Biomarcadores , Lípidos , Metales , Humanos , Femenino , Embarazo , Biomarcadores/sangre , Estudios Transversales , Adulto , Metales/sangre , Metales/orina , Lípidos/sangre , Exposición Materna/estadística & datos numéricos , Triglicéridos/sangre , HDL-Colesterol/sangre , Dislipidemias/inducido químicamente , Contaminantes Ambientales/sangre , Adulto Joven , LDL-Colesterol/sangreRESUMEN
BACKGROUND: The influence of adherence to a planetary health diet (PHD) proposed by the EAT-Lancet Commission on cardiovascular disease (CVD) is inconclusive. Besides, whether genetic susceptibility to CVD can modify the association of PHD with CVD remains unknown. OBJECTIVE: We aimed to investigate the association between adherence to PHD and CVD, and to evaluate the interaction between PHD and genetic predisposition to CVD. METHODS: This study included 114,165 participants who completed at least two 24-h dietary recalls and were initially free of CVD from the UK Biobank. PHD score was calculated to assess adherence to PHD. Genetic risk was evaluated using the polygenic risk score. Incidence of total CVD, ischemic heart disease (IHD), atrial fibrillation (AF), heart failure (HF), and stroke were identified via electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.9 y, 10,071 (8.8%) incident CVD cases were documented. Compared with participants with the lowest adherence to PHD, HRs (95% CIs) for total CVD, IHD, AF, HF, and stroke among those with the highest adherence were 0.79 (0.74, 0.84), 0.73 (0.67, 0.79), 0.90 (0.82, 0.99), 0.69 (0.59, 0.82), and 0.88 (0.75, 1.04), respectively. No significant interaction between the genetic risk of CVD and PHD was observed. Participants with high genetic risk and low PHD score, as compared with those with low genetic risk and high PHD score, had a 48% (95% CI: 40%, 56%) higher risk of CVD. The population-attributable risk (95% CI) of CVD for poor adherence to PHD ranged from 8.79% (5.36%, 12.51%) to 14.00% (9.00%, 18.88%). CONCLUSIONS: These findings suggest that higher adherence to PHD was associated with lower risk of total CVD, IHD, AF, and HF in populations across all genetic risk categories.
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AIM: To evaluate the prospective associations of nighttime sleep duration, midday napping, and sleep quality during early pregnancy with gestational diabetes mellitus (GDM) risk among Chinese pregnant women. METHODS: Sleep-related information was assessed by the Pittsburgh Sleep Quality Index in baseline surveys during the 6-15 (mean 10.3) gestational weeks. GDM was diagnosed during 24-28 gestational weeks according to the Chinese Guidelines on Diagnosis and Management of Hyperglycemia in Pregnancy (2022). Multivariable logistic regression models with adjustments for socio-demographic and lifestyle factors were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations of sleep traits with GDM risk. RESULTS: We identified 503 incident GDM cases among 6993 participants. Compared with women who slept for 7-9 hours/night in early pregnancy, those who slept <7 hours/night showed a higher risk of GDM (OR, 1.75; 95 % CI: 1.20-2.54), whereas those who slept >9 hours/night showed no significant association for GDM risk (OR, 1.01; 95 % CI: 0.78-1.30). Compared with women with absolutely no napping, those with ≤60 and > 60 min/day midday napping showed no significant association for GDM risk (OR, 0.82; 95 % CI: 0.64-1.05 for ≤60 min/day midday napping; OR, 0.87; 95 % CI: 0.66-1.15 for >60 min/day midday napping). Poor sleep quality was not associated with GDM risk compared with good quality (OR, 0.90; 95 % CI: 0.72-1.12). CONCLUSION: A short nighttime sleep duration during early pregnancy was associated with a higher risk of GDM, which was independent of midday napping, sleep quality and lifestyle factors.
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Diabetes Gestacional , Calidad del Sueño , Sueño , Humanos , Femenino , Diabetes Gestacional/epidemiología , Embarazo , Estudios Prospectivos , China/epidemiología , Adulto , Sueño/fisiología , Factores de Riesgo , Factores de Tiempo , Estudios de Cohortes , Encuestas y Cuestionarios , Duración del SueñoRESUMEN
BACKGROUND: The poor nutritional characteristics and potentially harmful molecules in ultraprocessed foods (UPFs) are risk factors for diabetic microvascular complications. However, the evidence regarding UPFs and diabetic microvascular complications remains limited. OBJECTIVES: We aimed to evaluate the associations between UPF consumption and risk of diabetic microvascular complications, to examine the underlying biological pathways (e.g., inflammation and lipid profile), and to identify whether the associations differ by type of UPF dietary patterns. METHODS: We included a prospective cohort of United Kingdom Biobank participants with type 2 diabetes (T2D) having at least one 24-h dietary recall (N = 5685). UPFs were defined using the Nova classification. Principal component analysis was used to derive UPF consumption patterns. Associations of UPFs and their consumption patterns with microvascular complications were assessed using Cox proportional hazards regression models. Mediation analyses were used to estimate the mediating effects of 22 biomarkers. RESULTS: During a median of 12.7 y of follow-up, 1243 composite microvascular complications events occurred (599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events). Five consumption patterns were identified (spread and bread, cereal prepared with liquids, dairy-based products, sugary beverage and snack, and mixed beverage and savory snack patterns). A 10% increment in the proportion of UPF was associated with higher hazards of the composite microvascular complications (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.03, 1.13) and diabetic kidney disease (HR: 1.13; 95% CI: 1.06, 1.20). Triglycerides, C-reactive protein, and body mass index collectively explained 22.0% (9.6%-43.0%) of the association between UPF intake and composite microvascular complications. Pattern high in mixed beverage and savory snack was associated with a higher risk of composite microvascular complications. CONCLUSIONS: Higher UPF consumption was associated with higher risks of diabetic microvascular complications, and the association was partly mediated through multiple potential ways.
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BACKGROUND: Inconsistent associations between antenatal depression and fetal birth weight were reported previously, and little is known about the dynamic changes and long-term cumulative effect of antenatal depression during pregnancy. METHODS: Participants were from the Tongji-Huaxi-Shuangliu Birth Cohort. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale in early, middle, and late pregnancy respectively. Trajectories of antenatal depression were assessed using the latent class mixed model. The percentage of days with depression (PDD) and frequency of antenatal depression were measured to assess the cumulative exposure. Multivariable logistic regression models were used to evaluate the associations of antenatal depression with macrosomia and large for gestational age (LGA). RESULTS: We identified four distinct trajectories, including the low stable group (n = 1,327, 27.99 %), the moderate stable group (n = 2,610, 55.05 %), the peak group (n = 407, 8.58 %), and the valley group (n = 397, 8.37 %). Compared with the low stable group, the valley group showed a higher risk of macrosomia (OR, 1.98; 95 % CI, 1.17, 3.38) and LGA (OR, 1.44; 95 % CI, 1.002, 2.09); the peak group showed a higher risk of LGA (OR, 1.52; 95 % CI, 1.07, 2.16), but the association was not significant for macrosomia (OR, 1.47; 95 % CI, 0.85, 2.55). Consistently, cumulative antenatal depression was also positively associated with the risks of macrosomia and LGA. LIMITATION: The antenatal depression was self-reported using a screening scale and information bias could not be ruled out. CONCLUSION: Certain trajectories and cumulative exposure of antenatal depression were associated with higher risks of high birth weight.
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Peso al Nacer , Depresión , Macrosomía Fetal , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Adulto , Macrosomía Fetal/epidemiología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , Depresión/epidemiología , Depresión/psicología , China/epidemiología , Recién Nacido , Factores de Riesgo , Estudios de Cohortes , Modelos Logísticos , Escalas de Valoración Psiquiátrica , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicologíaRESUMEN
In situ CuI-mediated cyclization methodology helped yield benzimidazoles with different substitution manner, such as 1,2-diarylbenzimidazoles (4 and 5) and 1-arylbenzimidazoles (6-15). The result of structure-activity relationship (SAR) study confirmed the significance of the 5,6,7-trimethoxybenzimidazole moiety, and the representative derivatives (8-10) exhibited marked antiproliferative activity against A549, HCT-116, and PC-3 cells; in addition, they are able to inhibit the polymerization of tubulin. Among them, compound 10 inhibited the growth of A549, HCT-116, and PC-3 cells with a mean IC50 value of 0.07 µM, and its IC50 value of tubulin polymerization is 0.26 µM.
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[This corrects the article DOI: 10.1039/D3RA01927F.].
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Prostate cancer metastasis is associated with poor prognosis and is difficult to treat clinically. Numerous studies have shown that Asiatic Acid (AA) has antibacterial, anti-inflammatory, and antioxidant effects. However, the effect of AA on prostate cancer metastasis is still unclear. This purpose of this study is to investigate the effect of AA on prostate cancer metastasis and to better understand its molecular mechanisms of action. Our results indicate that AA ≤ 30 µM did not influence cell viability and cell cycle distribution in PC3, 22Rv1 and DU145 cells. AA inhibited the migratory and invasive capabilities of three prostate cancer cells to be due to its effects on Snail, but did not have activity on Slug. We observed that AA inhibited the Myeloid zinc finger 1 (MZF-1) and ETS Like-1 (Elk-1) protein interaction and affected the complex's binding capacity to the Snail promoter region, ultimately blocking Snail transcription activity. Kinase cascade analysis revealed that phosphorylation of MEK3/6 and p38MAPK was inhibited by AA treatment. Moreover, knockdown of p38MAPK enhanced AA-suppressed protein levels of MZF-1, Elk-1, and Snail, suggesting that p38MAPK influences prostate cancer cell metastasis. These results provide promise for AA as a future candidate in the development of drug therapies to prevent or treat prostate cancer metastasis.