RESUMO
Metastasis is an important contributor to increased mortality rates in non-small cell lung cancer (NSCLC). The TGF-ß signalling pathway plays a crucial role in facilitating tumour metastasis through epithelial-mesenchymal transition (EMT). Glycolysis, a key metabolic process, is strongly correlated with NSCLC metastasis. Pirfenidone (PFD) has been shown to safely and effectively inhibit TGF-ß1 in patients with lung diseases. Furthermore, TGF-ß1 and glycolysis demonstrate an interdependent relationship within the tumour microenvironment. Our previous study demonstrated that PFD effectively inhibited glycolysis in NSCLC cells, prompting further investigation into its potential antitumour effects in this context. Therefore, the present study aims to investigate the potential antitumour effect of PFD in NSCLC and explore the relationship among TGF-ß1, glycolysis and EMT through further experimentation. The antitumour effects of PFD were evaluated using five different NSCLC cell lines and a xenograft tumour model. Notably, PFD demonstrated a significant antitumour effect specifically in highly glycolytic H1299 cells. To elucidate the underlying mechanism, we compared the efficacy of PFD after pretreatment with either TGF-ß1 or a TGF-ß receptor inhibitor (LY2109761). The energy metabolomics analysis of tumour tissue demonstrated that PFD, a chemosensitizing agent, reduced lactate and ATP production, thereby inhibiting glycolysis and exerting synergistic antineoplastic effects. Additionally, PFD combined with cisplatin targeted TGF-ß1 to inhibit glycolysis during EMT and enhanced the chemosensitization of A549 and H1299 cells. The magnitude of the anticancer effect exhibited by PFD was intricately linked to its metabolic properties.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piridonas , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/patologia , Reprogramação Metabólica , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral , AnimaisRESUMO
Environmental arsenic exposure is a significant global public health concern. Previous studies have demonstrated the association between arsenic-induced liver injury and oxidative stress as well as ferroptosis. However, the knowledge of the interactions among these mechanisms remains limited. Moreover, there is a lack of research on potential therapeutic interventions for liver injury resulting from arsenic exposure. To address these limitations, we established a rat model with liver injury caused by arsenic exposure and investigated the impact of the nuclear factor E2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4) signaling pathway and ferroptosis on arsenic-induced liver injury. Our findings revealed that arsenic increased Nrf2 expression and decreased GPx4 expression in the rat liver. This was accompanied by a substantial generation of reactive oxygen species and disruption of the antioxidant defense system, ultimately promoting liver injury through ferroptosis. Subsequently, we conducted intervention experiments using Rosa roxburghii Tratt (RRT) in rats exposed to arsenic. The results showed that the detrimental effects mentioned earlier were partially alleviated following RRT intervention. This study offers preliminary evidence that persistent activation of Nrf2 by arsenic triggers an adaptive antioxidant response, leading to liver injury through the promotion of ferroptosis. Additionally, we discovered that RRT inhibits Nrf2-mediated adaptive antioxidant responses by reducing hepatic ferroptosis, thereby mitigating liver injury caused by arsenic exposure in rats. Our study contributes to a deeper understanding of the molecular mechanisms underlying liver injury resulting from arsenic exposure. Furthermore, our findings may facilitate the identification of a potential edible and medicinal plant extracts that could be utilized to develop a more effective adjunctive treatment approach.
Assuntos
Arsênio , Doença Hepática Crônica Induzida por Substâncias e Drogas , Animais , Ratos , Antioxidantes , Fator 2 Relacionado a NF-E2RESUMO
BACKGROUND: Little is known about the association between a plant-based diet and the risk of gallstone disease (GD), especially in developing counties. We tested the hypothesis that shifting dietary patterns would be related to the risk of GD, and that the Mediterranean diet (MED) adjusted for China would be beneficial for lowering risk of GD. METHODS: Data were extracted from the baseline survey of the China Multi-Ethnic Cohort study. An alternative Mediterranean diet (aMED) score was assessed based on a food frequency questionnaire, and three posteriori dietary patterns (the modern dietary pattern, the coarse grain dietary pattern, and the rice dietary pattern) were identified using factor analysis. Multivariable logistic regression models were developed to evaluate the association between dietary patterns and GD risks. RESULTS: A total of 89,544 participants were included. The prevalence of GD was 7.5%. Comparing the highest with lowest quintiles, aMED was associated with an increased risk of GD (OR 1.13; 95% CI, 1.04-1.24; Ptrend = 0.003), whereas the rice dietary pattern was inversely related to GD risk (OR 0.79; 95% CI, 0.71-0.87; Ptrend < 0.001). In stratified analysis, the rice dietary pattern had a stronger inverse association in the subgroups of females, older, urban, and overweight participants, and those with diabetes-factors associated with higher rates of GD in previous studies. CONCLUSION: Higher adherence to the rice dietary pattern was associated with a lower risk of GD. For high-risk populations, making some shift to a traditional agricultural diet might help with primary prevention of GD.
Assuntos
Dieta Mediterrânea , Cálculos Biliares , Adulto , Humanos , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Dieta , População do Leste Asiático , Cálculos Biliares/epidemiologia , Japão , Fatores de RiscoRESUMO
Arsenic exposure is a major environmental public health challenge worldwide. As typical manifestations for arsenic exposure, the pathogenesis of arsenic-induced skin lesions has not been fully elucidated, as well as the lack of effective control measures. In this study, we first determined the short-term and high-dose arsenic exposure can increase the apoptosis rates, while long-term low-dose arsenic exposure decrease the apoptosis rates. Then, the HaCaT cells with knockdown and overexpression of CCAAT-enhancer-binding protein ß (CEBPB) and extracellular signal-regulated kinase (ERK) were constructed. The results demonstrate that knockdown of CEBPB and ERK can reduce NaAsO2 -induced cell apoptosis by inhibiting ERK/CEBPB signaling pathway and vice versa. Further cells were treated with Kaji-Ichigoside F1 (KF1). The results clearly show that KF1 can decrease the arsenic-induced cell apoptosis rates and the expression of ERK/CEBPB signaling pathway-related genes. These results provide evidence that ERK/CEBPB signaling pathway acts as a double-edged sword in arsenic-induced skin damage. Another interesting finding was that KF1 can alleviate arsenic-induced skin cell apoptosis by inhibiting the ERK/CEBPB signaling pathway. This study will contribute to a deeper understanding of the mechanisms of arsenic-induced skin cell apoptosis, and our findings will help to identify a potential food-borne intervention in arsenic detoxification.
Assuntos
Arsênio , MAP Quinases Reguladas por Sinal Extracelular , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Arsênio/toxicidade , Transdução de Sinais , Apoptose , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/farmacologiaRESUMO
8-Epidiosbulbin E acetate (EEA), a furan-containing diterpenoid lactone, is one of main component of Dioscorea bulbifera L. (DBL). It has been reported that EEA induces severe hepatotoxicity in mice and that its hepatotoxicity is associated with metabolic activation. The present study demonstrated that exposure to EEA (50, 100 or 200 µM) induced DNA damage, including significant DNA fragmentation, increases of tail DNA and olive tail moment, H2AX phosphorylation and PARP-1 activation, in cultured mouse primary hepatocytes. Similar observation was obtained in mice administered EEA at 50, 100 or 200 mg/kg. Pre-treatment with 10 µM ketoconazole (KTC), 200 µM vitamin C (VC), or 200 µM glutathione ethyl ester (GSH-OEt) reversed the over-production of reactive oxygen species (ROS) induced by EEA and attenuated susceptibility of hepatocytes to EEA-induced cytotoxicity and DNA damage in mouse primary hepatocytes. In contrast, pre-treatment with 1.0 mM L-buthionine sulfoximine (BSO) potentiated over-production of ROS, cytotoxicity and DNA damage induced by EEA. In summary, EEA induced DNA damage in cultured primary hepatocytes and the liver of mice. ROS, possibly along with DNA alkylation, participated in the observed DNA damage.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Diterpenos , Ativação Metabólica , Animais , Butionina Sulfoximina/metabolismo , Butionina Sulfoximina/farmacologia , DNA/metabolismo , Dano ao DNA , Diterpenos/farmacologia , Glutationa/metabolismo , Camundongos , Espécies Reativas de OxigênioRESUMO
Different from developed countries, there is a paucity of research examining how the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets relate to lipids in less-developed ethnic minority regions (LEMR). A total of 83 081 participants from seven ethnic groups were retrieved from the baseline data of the China Multi-Ethnic Cohort study, which was conducted in less-developed Southwest China between May 2018 and September 2019. Multivariable linear regression models were then used to examine the associations of the DASH and alternative Mediterranean diet (AMED) scores, assessed by modified DASH score and AMED, as well as their components with total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, TAG and TC/HDL-cholesterol. The DASH scores were negatively associated with TC, HDL-cholesterol and TAG. Comparing the highest quintiles with the lowest DASH scores, TC decreased 0·0708 (95 % CI -0·0923, -0·0493) mmol/l, HDL-cholesterol decreased 0·0380 (95 % CI -0·0462, -0·0299) mmol/l and TAG decreased 0·0668 (95 % CI -0·0994, -0·0341) mmol/l. The AMED scores were negatively associated with TC, LDL-cholesterol and HDL-cholesterol. Comparing the highest quintiles with the lowest AMED scores, TC decreased 0·0816 (95 % CI -0·1035, -0·0597) mmol/l, LDL-cholesterol decreased 0·0297 (95 % CI -0·0477, -0·0118) mmol/l and HDL-cholesterol decreased 0·0275 (95 % CI -0·0358, -0·0192) mmol/l. Although both the DASH diet and the Mediterranean diet were negatively associated with blood lipids, those associations showed different patterns in LEMR, particularly for TAG and HDL-cholesterol.
Assuntos
Dieta Mediterrânea , Abordagens Dietéticas para Conter a Hipertensão , Humanos , Etnicidade , Estudos de Coortes , Minorias Étnicas e Raciais , Grupos Minoritários , Lipídeos , HDL-Colesterol , LDL-ColesterolRESUMO
Previous studies assessing adverse health have traditionally focused on a single environmental exposure, failing to reflect the reality of various exposures present simultaneously. Air pollution, ambient temperature and greenness have been proposed as critical environmental factors associated with metabolic syndrome (MetS). However, evidence exploring their joint relationships with MetS is needed for identifying interactive factors and developing more targeted public health interventions. The baseline data was obtained from China Multi-Ethnic Cohort (CMEC). Environmental data of air pollutants (PM2.5, O3) and NDVI for greenness was calculated from satellites data. Ambient temperature data were obtained from European Center for Medium-Range Weather Forecasts (ECMWF). MetS was classified based on National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) using anthropometric measures and biomarkers. Logistic regression models were utilized to examine the combined relationship of MetS with three-year exposure to air pollutants, temperature and NDVI. Relative excess risk due to interaction (RERI) was calculated to evaluate interaction on an additive scale. We found associations between prevalent MetS and interquartile range (IQR) increases in PM2.5 (OR: 1.38; 95% confidence interval [95% CI]: 1.23, 1.55) and O3 (OR: 1.15; 95% CI: 1.09, 1.22). Additive and multiplicative interactions were observed between air pollutants and temperature exposure. Compared to low-temperature level, the relationship between PM2.5 and MetS attenuated (RERI: 0.22, 95% CI: 0.44, -0.04) at high-temperature level, while the relationship between O3 and MetS enhanced (RERI: 0.05, 95% CI: 0.02, 0.11). At low NDVI 250 m, the association between PM2.5 and MetS was stronger (RERI: 0.13, 95% CI: 0.05, 0.19) with high NDVI 250 m as the reference group. Our findings showed that ambient temperature and residential greenness could affect the relationship between air pollutants and MetS.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Síndrome Metabólica , Adulto , China , Exposição Ambiental , Humanos , Material Particulado , TemperaturaRESUMO
BACKGROUND: The association between serum uric acid (SUA) and the components of dyslipidaemia and their dose-response relationships have not been thoroughly explored. This study assessed the relationship between SUA and each dyslipidaemia component in Dong, Miao, and Bouyei populations in Guizhou by sex and ethnicities and investigated the dose-response relationship. METHODS: In total, 16,092 participants aged 30-79 years from The China Multi-Ethnic Cohort (CMEC) Study were examined. Multivariable logistic regression models were applied to explore the relationship between SUA and each dyslipidaemia component by sex and three ethnicities. The dose-response associations between SUA and various dyslipidaemias were investigated using restricted cubic spline regression. RESULTS: After controlling for confounding factors, the SUA level in total participants positively correlated with each dyslipidaemia component, and women had higher odds ratios (ORs) for each dyslipidaemia component than men (P for trend < 0.001). At the SUA level > 6.37 mg/dL, ORs (95% CI) for dyslipidaemia in the Dong, Miao and Bouyei were 2.89 (2.00-4.19), 2.43 (1.70-3.48), and 3.26 (2.23-4.78), respectively. When the SUA concentration increased by 1 mg/dL, the ORs (95% CI) for total dyslipidaemia was 1.31 (1.24-1.37). A positive dose-response but nonlinear association was found between SUA and total dyslipidaemia, high total cholesterol, and low HDL, whereas an inverse U-shaped association was found between SUA and high LDL-C ( P-nonlinear< 0.0001). CONCLUSION: The SUA level was positively correlated with each dyslipidaemia component in Dong, Miao, and Bouyei adults, and sex and ethnic differences were also found. A nonlinear dose-response relationship was found between SUA levels and dyslipidaemia and its components. Further research is warranted to investigate the causal link between SUA levels and dyslipidaemia incidence.
Assuntos
Dislipidemias , Ácido Úrico , Adulto , Idoso , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Farmers are the integral members of rural communities. In the present study, we determined the association between occupational physical activity (OPA) of farmers and dyslipidaemia. METHODS: We included 7649 farmers from The China Multi-Ethnic Cohort (CMEC) Study. The working modes of all farmers were divided into four types according to their self-reported seasonal changes in farming work and/or other job changes (1: no change; 2: changing job; 3: seasonal changes; and 4: seasonal and job changes). OPA was self-reported, and the OPA levels in the four groups were classified as Q1, Q2-Q3, and Q4 by quantile. Dyslipidaemia was defined as the presence of abnormalities in lipid indicators. Binary logistic regression was used to estimate the association between OPA and dyslipidaemia. RESULTS: Compared with those in the no change group, the participants in other three groups were younger with lower level of education, annual income, and leisure-time physical activity (LTPA). Active OPA could reduce the risk of dyslipidaemia in the no change [men: odds ratios (OR) = 0.21, 95% confidence intervals (CI): 0.07-0.64; women: OR = 0.43, 95% CI: 0.20-0.93] and seasonal change (men: OR = 0.46, 95% CI: 0.27-0.77; women: OR = 0.59, 95% CI: 0.41-0.86) groups. However, in the seasonal and job change group (men: OR = 3.23, 95% CI: 1.06-9.80; women: OR = 3.24, 95% CI: 1.42-7.41), active OPA increased the risk of dyslipidaemia. CONCLUSIONS: Different OPA levels might lead to differences in association with blood lipid levels. Thus, OPA guidelines must be developed for farmers, especially for those who experience seasonal changes in farming work and job changes.
Assuntos
Dislipidemias , Atividades de Lazer , China/epidemiologia , Estudos de Coortes , Dislipidemias/epidemiologia , Exercício Físico , Fazendeiros , Feminino , Humanos , MasculinoRESUMO
Exposure to coal-burning arsenic leads to an increased risk of cancer, multi-systems damage and chronic diseases, with DNA methylation one potential mechanism of arsenic toxicity. There are few studies on genome-wide methylation in the coal-burning arsenic poisoning population. Illumina 850 K methylation beadchip is the most suitable technology for DNA methylation of epigenome-wide association analysis. This study used 850 K to detect changes in Genome-wide DNA methylation in whole blood samples of 12 patients with coal-burning arsenic poisoning ( Arsenic poisoning group) and four healthy control participants (Healthy control group). There is clearly abnormal genome-wide DNA methylation in coal-burning arsenic poisoning, with 647 significantly different methylation positions, 524 different methylation regions and 335 significantly different methylation genes in arsenic poisoning patients compared with healthy controls. Further functional analysis of Gene ontology (GO) and Kyoto encyclopedia of genes (KEGG) found 592 GO items and 131 KEGG pathways between patients of coal-burning arsenic poisoning and healthy control. Then, analysis of gene degree and combined-score identified NAPRT1, NT5C3B, NEDD4L, SLC22A3 and RAB11B as target genes. Further validation by qRT-PCR indicates that mRNA expression of five genes changes significantly in the arsenic poisoning group (n = 72) compared to the healthy control group (n = 72). These results showed the genome-wide methylation pattern and highlighted five critical genes within the coal-burning arsenic poisoning population that involve Nicotinate and nicotinamide metabolism, Choline metabolism in cancer, and Ubiquitin mediated proteolysis. Next, the methylation profile of coal burning arsenic poisoning will be further excavation and the mechanism of coal burning arsenic poisoning will be further explored from five genes related pathways and functions.
Assuntos
Intoxicação por Arsênico , Arsênio , Humanos , Metilação de DNA/genética , Intoxicação por Arsênico/genética , Carvão Mineral , DNARESUMO
Chronic exposure to high-dose inorganic arsenic through groundwater, air, or food remains a major environmental public health issue worldwide. Apoptosis, a method of cell death, has recently become a hot topic of research in biology and medicine. Previous studies have demonstrated that extracellular signal-regulated kinase (ERK) is related to arsenic-induced apoptosis. However, the reports are contradictory, and the knowledge of the above-mentioned mechanisms and their mutual regulation remains limited. In this study, the associations between the TGF-ß1/ERK signaling pathway and arsenic-induced cell apoptosis were confirmed using the HaCaT cell model. The relative expressions of the indicators of the TGF-ß1/ERK signaling pathway, apoptosis-related genes (cytochrome C, caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9, and Bax), the mitochondrial membrane potential, and the total apoptosis rate were significantly increased (P < .05), while the expression of the antiapoptosis gene Bcl-2 was significantly decreased (P < .05) in cells of the group exposed to arsenic. Moreover, the results demonstrated that the ERK inhibitor (PD98059) and TGF-ß1 inhibitor (LY364947) could inhibit the activation of the ERK signaling pathway, thereby reducing the mitochondrial membrane potential, the total apoptosis rate, and the expression of pro-apoptosis-related genes in the cells, while the expression of the antiapoptosis gene Bcl-2 was significantly increased (P < .05). By contrast, the recombinant human TGF-ß1 could promote apoptosis of the HaCaT cells by increasing the activation of the ERK signaling pathway (P < .05). These results indicate that inorganic arsenic promotes the apoptosis of human immortal keratinocytes through the TGF-ß1/ERK signaling pathway.
Assuntos
Arsênio , MAP Quinases Reguladas por Sinal Extracelular , Apoptose , Arsênio/metabolismo , Arsênio/toxicidade , Caspase 3/metabolismo , Caspase 9/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Cataracts are an ailment representing the leading cause of blindness in the world. The pathogenesis of cataracts is not clear, and there is no effective treatment. An increasing amount of evidence shows that oxidative stress and autophagy in lens epithelial cells play a key role in the occurrence and development of cataracts. Buddleja officinalis Maxim flavonoids (BMF) are natural antioxidants and regulators that present anti-inflammatory and anti-tumor effects, among others. In this study, we optimized the extraction method of BMFs and detected three of their main active monomers (luteolin, apigenin, and acacetin). In addition, a model of oxidative damage model using rabbit lens epithelial cells induced by hydrogen peroxide (H2O2). By detecting the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and OH (OH), the expression of autophagosomes and autolysosomes were observed after MRFP-GFP-LC3 adenovirus was introduced into the cells. Western blotting was used to detect the expression of Beclin-1 and P62. Our research results showed that the optimal extraction parameters to obtain the highest yield of total flavonoids were a liquid−solid ratio of 1:31 g/mL, an ethanol volume fraction of 67%, an extraction time of 2.6 h, and an extraction temperature of 58 °C. Moreover, the content of luteolin was 690.85 ppb, that of apigenin was 114.91 ppb, and the content of acacetin was 5.617 ppb. After oxidative damage was induced by H2O2, the cell survival rate decreased significantly. BMFs could increase the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decrease the levels of malondialdehyde (MDA) and OH (OH). After the MRFP-GFP-LC3 virus was introduced into rabbit lens epithelial cells and detecting the expression of P62 and Beclin-1, we found that the intervention of BMF could promote the binding of autophagosomes to lysosomes. Compared with the model group, the level of P62 in the low-, middle-, and high-dose groups of BMF was significantly down-regulated, the level of Beclin-1 was significantly increased, and the difference was statistically significant (p < 0.05). In other words, the optimized extraction method was better than others, and the purified BMF contained three main active monomers (luteolin, apigenin, and acacetin). In addition, BMFs could ameliorate the H2O2-induced oxidative damage to rabbit lens cells by promoting autophagy and regulating the level of antioxidation.
Assuntos
Buddleja , Catarata , Animais , Coelhos , Peróxido de Hidrogênio/farmacologia , Flavonoides/farmacologia , Proteína Beclina-1/metabolismo , Apigenina/farmacologia , Luteolina/farmacologia , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo , Autofagia , Malondialdeído/metabolismo , Glutationa Peroxidase/metabolismoRESUMO
Semaphorin (Sema) 3A and Sema 4A are immunomodulatory molecules with a common receptor, neuropilin-1 (NRP-1), on the immune cells. Sema 3A binds to NRP-1 and inhibits T cell activation and inflammation, while Sema 4A binds to NRP-1 and promotes T cell activation and inflammation. These molecules are associated closely with the regulation of protein kinase B (AKT)/nuclear factor-kappaB (NF-κB) signaling, which are poorly understood in arsenic toxicity. The present study explored the role of Sema 3A or Sema 4A in arsenic-induced hepatotoxicity in mice. Arsenic exposure induced hepatic injury and resulted in the activations of p-AKT2, NF-κB p65, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, downregulation of Sema 3A, and upregulation of Sema 4A or NRP-1. Interestingly, intervention with anti-Sema 4A antibody showed the mitigation of arsenic-induced hepatotoxicity, accompanied by the downregulation of Sema 4A, rebound of Sema 3A, and upregulation of NRP-1. And, the inflammatory signaling p-AKT2 or NF-κB p65, and NLRP3 inflammasome showed a downregulation compared with arsenic treatment group. In contrast, anti-Sema 3A antibody intervention did not show the significant effect in the histopathological features compared with arsenic treatment group. In conclusion, the anti-Sema 4A antibody antagonizes arsenic-induced hepatotoxicity in mice and may be involved in the inhibitions of AKT2/NF-κB and NLRP3 inflammatory signaling mediated synergistically by Sema 4A or Sema 3A and their receptor NRP-1.
Assuntos
Arsênio/toxicidade , Autoanticorpos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Semaforinas/antagonistas & inibidores , Animais , Autoanticorpos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Relação Dose-Resposta a Droga , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Semaforinas/metabolismoRESUMO
BACKGROUND: Cardiovascular risk factors in Chinese ethnic minority groups are rarely reported. OBJECTIVE: To quantify the cardiovascular risk factors in Miao Chinese adults and to examine the association of health behaviors and metabolic risk factors with dyslipidemia. METHODS: A cross-sectional analysis was conducted using baseline data from the China Multi-Ethnic Cohort (CMEC) study. A representative sample of 5559 Miao participants aged 30 to 79 years were surveyed and given physical and laboratory exams. The proportion of behavioral and metabolic risk factors were described in ethnic Miao adults. Logistic regression was utilized to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the association between health behaviors and metabolic risk factors with dyslipidemia. RESULTS: In Miao Chinese adults, the prevalence of dyslipidemia was 32.8%. After multivariate adjustment, subjects with poor waist-to-hip ratio (WHR), body mass index (BMI), fasting blood glucose (FBG) and blood pressure (BP) were more likely to have higher risk of triglycerides (TG) abnormality, regardless of gender and age. Furthermore, the strongly association was detected between poor WHR and low density lipoprotein cholesterol (LDL-C) abnormality (adjusted OR = 5.24, 95%CI: 2.42-11.34) in the older subgroup (≥ 60 years). Males who current smoking were an independent risk factor only for high density lipoprotein cholesterol (HDL-C) abnormality (adjusted OR = 1.44, 95%CI: 1.05-1.99). However, in the subgroup age, current smoker were at greater risk of high TG and low HDL-C. Males with regular drinking were less likely to be high LDL-C (adjusted OR = 0.51, 95%CI: 0.32-0.81). CONCLUSIONS: The present findings indicated that Miao adults with metabolic risk factors were at greater risk of dyslipidemia.
Assuntos
Dislipidemias , Etnicidade , Adulto , Idoso , Índice de Massa Corporal , China/epidemiologia , HDL-Colesterol , Estudos de Coortes , Estudos Transversais , Dislipidemias/epidemiologia , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Minoritários , Obesidade , Fatores de Risco , TriglicerídeosRESUMO
Environmental exposure to arsenic is a major public health challenge worldwide. Growing evidence indicates that coal-burning arsenic can cause hepatic oxidative damage. However, the value of Rosa roxburghii Tratt (RRT) with antioxidant properties on arsenic-caused hepatic oxidative damage has never been elucidated yet. In this study, the animals were exposed to coal-burning arsenic (10 mg/kg bw) for 90 days and the result showed a loss of body weight, impaired liver function and liver diseases, increased hepatic oxidative damage and metabolic disorder of multiple elements including selenium, copper, zinc which were related to synthesis of antioxidant enzymes. Another finding is that RRT restored the abnormal liver function and alleviated the procedures of liver diseases of arsenic poisoning rats. In addition, it could also effectively reduce the degree of oxidative damage in serum and liver, and restore the activity of some antioxidant enzymes. Importantly, RRT reversed the content of most disordered elements caused by arsenic in liver and reduced the excretion of several essential elements in urine, including selenium, copper and zinc. Our study provides some limited evidence that RRT can alleviate coal-burning arsenic-induced liver damage induced by regulating elemental metabolic disorders and liver oxidation and antioxidant balance. The study provides a scientific basis for further studies of the causes of the arsenic-induced liver damage, and effective intervention strategies.
Assuntos
Intoxicação por Arsênico/patologia , Arsênio/toxicidade , Fígado/efeitos dos fármacos , Rosa/metabolismo , Animais , Antioxidantes/metabolismo , Arsênio/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
Circulating tumor cells (CTCs) shed from primary tumors must overcome the cytotoxicity of immune cells, particularly natural killer (NK) cells, to cause metastasis. The tumor microenvironment (TME) protects tumor cells from the cytotoxicity of immune cells, which is partially executed by cancer-associated mesenchymal stromal cells (MSCs). However, the mechanisms by which MSCs influence the NK resistance of CTCs remain poorly understood. This study demonstrates that MSCs enhance the NK resistance of cancer cells in a gap junction-dependent manner, thereby promoting the survival and metastatic seeding of CTCs in immunocompromised mice. Tumor cells crosstalk with MSCs through an intercellular cGAS-cGAMP-STING signaling loop, leading to increased production of interferon-ß (IFNß) by MSCs. IFNß reversely enhances the type I IFN (IFN-I) signaling in tumor cells and hence the expression of human leukocyte antigen class I (HLA-I) on the cell surface, protecting the tumor cells from NK cytotoxicity. Disruption of this loop reverses NK sensitivity in tumor cells and decreases tumor metastasis. Moreover, there are positive correlations between IFN-I signaling, HLA-I expression, and NK tolerance in human tumor samples. Thus, the NK-resistant signaling loop between tumor cells and MSCs may serve as a novel therapeutic target.
Assuntos
Interferon beta , Células Matadoras Naturais , Células-Tronco Mesenquimais , Células Neoplásicas Circulantes , Nucleotidiltransferases , Transdução de Sinais , Microambiente Tumoral , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Animais , Células Matadoras Naturais/imunologia , Camundongos , Interferon beta/metabolismo , Interferon beta/imunologia , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Humanos , Células Neoplásicas Circulantes/imunologia , Células Neoplásicas Circulantes/metabolismo , Microambiente Tumoral/imunologia , Proteínas de Membrana/metabolismo , Modelos Animais de Doenças , Linhagem Celular TumoralRESUMO
Ferroptosis is a unique form of programmed cell death driven by iron-dependent phospholipid peroxidation that was proposed in recent years. It plays an important role in processes of various trace element-related diseases and is regulated by redox homeostasis and various cellular metabolic pathways (iron, amino acids, lipids, sugars), as well as disease-related signaling pathways. Some limited pioneering studies have demonstrated ferroptosis as a mechanism for the health effects of essential trace elements and potentially toxic trace elements, with crosstalk among them. The aim of this review is to bring together research articles and identify key direct and indirect evidence regarding essential trace elements (iron, selenium, zinc, copper, chromium, manganese) and potentially toxic trace elements (arsenic, aluminum, mercury) and their possible roles in ferroptosis. Our review may help determine future research priorities and opportunities.
Assuntos
Ferroptose , Selênio , Oligoelementos , Cobre , Ferro , Oligoelementos/metabolismo , Oligoelementos/toxicidade , ZincoRESUMO
Breast cancer (BC) is one of the major public health challenges worldwide. Studies that address the new evidence on trends of BC are of great importance for preventing and controlling the occurrence and development of diseases and improving health. The aim of this study was to analyze the outcomes for the global burden of disease (GBD), incidence, deaths, and risk factors for BC from 1990 to 2019, and predict the GBD of BC until 2050 to inform global BC control planning efforts. In this study, the results show that the regions with low levels of socio-demographic index (SDI) will have the largest disease burden of BC in the future. The leading global risk factor for death attributable to BC in 2019 was metabolic risks, followed by behavioral risks. This study supports the worldwide urgent need for comprehensive cancer prevention and control strategies to reduce exposure, early screening, and improve treatment to effectively reduce the GBD of BC.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias da Mama/epidemiologia , Incidência , Fatores de Risco , Carga Global da DoençaRESUMO
OBJECTIVE: To estimate and compare sex-specific differences between metabolically healthy overweight/obesity (MHOO) and the risk of hypertension among Dong, Bouyei, and Miao adults in southwest China. METHODS: MHOO was diagnosed when the patient had a body mass index ≥24 kg/m2 and the presence of ≤1 component of metabolic syndrome. The main outcome was the occurrence of hypertension after the diagnosis or measurement by a physician at the baseline survey. Multivariate logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between MHOO and the risk of hypertension. RESULTS: We enrolled 16,433 Chinese Dong, Bouyei, and Miao adults. Using the metabolically healthy normal weight (MHNW) as a reference and after adjusting for confounders, the association between MHOO and the risk of hypertension was stronger in Dong (OR = 1.46, 95% CI: 1.07-2.00) and Miao (OR = 2.05, 95% CI: 1.48-2.85) men and did not exist in Bouyei men (OR = 1.14, 95% CI: 0.81-1.60). After adjusting for the age, the association between MHOO and the risk of hypertension was stronger in men than in women among Dong adults aged 30-59 years (OR = 1.64, 95% CI: 1.12-2.40) and did not differ between men and women among Dong adults aged 60-79 years or among Miao or Bouyei adults. CONCLUSION: The results of this study demonstrated sex-specific differences in the association between MHOO and the risk of hypertension and that sex-specific differences further differed among Dong, Bouyei, and Miao adults.
Assuntos
Hipertensão , Obesidade Metabolicamente Benigna , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Massa Corporal , China/epidemiologia , População do Leste Asiático , Minorias Étnicas e Raciais , Hipertensão/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/metabolismo , Sobrepeso/complicações , Sobrepeso/epidemiologia , Fatores de Risco , IdosoRESUMO
This study examined the potential of hyperspectral techniques for the rapid detection of characteristic indicators of yak meat freshness during the oxidation of yak meat. TVB-N values were determined by significance analysis as the characteristic index of yak meat freshness. Reflectance spectral information of yak meat samples (400-1000 nm) was collected by hyperspectral technology. The raw spectral information was processed by 5 methods and then principal component regression (PCR), support vector machine regression (SVR) and partial least squares regression (PLSR) were used to build regression models. The results indicated that the full-wavelength based on PCR, SVR, and PLSR models were shown greater performance in the prediction of TVB-N content. In order to improve the computational efficiency of the model, 9 and 11 characteristic wavelengths were selected from 128 wavelengths by successive projection algorithm (SPA) and competitive adaptive reweighted sampling (CARS), respectively. The CARS-PLSR model exhibited excellent predictive power and model stability.