RESUMO
Adolescents and young adults are the driving force of social development, and the prevalence of acute viral hepatitis (AVH) in this population cannot be ignored. At present, there are few studies on the disease burden of AVH in this age group, and most studies focus on chronic liver disease. In this study, we identified global trends in the burden of AVH among adolescents and young adults (15-29) to help policymakers implement precise disease interventions. In this observational study of disease trends, we collected data exclusively from the Global Burden of Disease (GBD) 2019 study. This study examined the trends in the prevalence, incidence and mortality of AVH among adolescents and young adults in 21 regions of the world from 2009 to 2019. Age-specific disease trends were analysed with a joinpoint regression model. The overall global disease burden of AVH declined. The prevalence rate per 100,000 people decreased from 316.13 in 2009 to 198.79 in 2019, the incidence rate decreased from 3245.52 in 2009 to 2091.93 in 2019, and the death rate decreased from 0.87 in 2009 to 0.43 in 2019. During the study period, the prevalence of hepatitis B virtues (HBV) in the young population decreased, but the downward trend of other types of hepatitis other than HBV was not obvious, especially HAV, which even showed an upward trend. Among adolescents and young adults aged 15-29 years, Western Saharan Africa had the highest prevalence of AVH in 2019. There were significant differences in mortality rates among different age groups; 20-24 was the age group with the highest mortality rate from 2009 to 2019, followed by the 15-19 and 25-29 age groups. Although the overall global AVH disease burden declined, some causes of AVH, such as HAV, showed an upward trend during the study period. In addition, the prevalence of AVH among adolescents and young adults in Asia and Africa was higher than that in other parts of the world and warrants more attention. Finally, more research should be conducted on mortality in the 20-24 age group.
Assuntos
Hepatite A , Hepatite B , Hepatite Viral Humana , Humanos , Adolescente , Adulto Jovem , Adulto , Hepatite Viral Humana/epidemiologia , Hepatite B/epidemiologia , Incidência , Prevalência , Doença Aguda , Efeitos Psicossociais da DoençaRESUMO
OBJECTIVES: This study aims to provide the most up-to-date temporal trends in incidence, mortality, and disability-adjusted life years (DALYs) of total gastric cancer in China from 1990 to 2019, and to predict the gastric cancer trends up to 2040. METHODS: Data for the incidence, mortality, and DALYs of stomach cancer in China from 1990 to 2019 were extracted from Global Burden of Disease Study 2019 (GBD 2019). We conducted joinpoint regression analysis to explore possible segmented changes in gastric cancer trends. We predicted gastric cancer trends up to 2040 using a Bayesian age-period-cohort model. RESULTS: The absolute incidence, mortality, and DALYs of gastric cancer increased from 1990 to 2019 in China. However, the age-standardized rates (ASRs) of incidence, mortality, and DALYs for gastric cancer decreased between 1990 and 2019, and the reductions were more pronounced for mortality and DALYs for gastric cancer. CONCLUSION: Our study generally reveals favorable declining trends of gastric cancer incidence and predicts that this will continue to 2040. However, the high contemporary incidence combined with China's aging population will likely slow or even reverse the declining trend in gastric cancer mortality.
Assuntos
Teorema de Bayes , Neoplasias Gástricas , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/mortalidade , Humanos , China/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Incidência , Idoso , Adulto , Estudos de Coortes , Anos de Vida Ajustados por Deficiência/tendências , Idoso de 80 Anos ou mais , Fatores Etários , Adulto JovemRESUMO
Carotenoids are important bioactive substances in breast milk, the profile of which is seldom studied. This study aimed to explore the profile of carotenoids in breast milk and maternal/cord plasma of healthy mother-neonate pairs in Shanghai, China, and their correlation with dietary intake. Maternal blood, umbilical cord blood and breast milk samples from five lactation stages (colostrum, transitional milk and early-, mid- and late-term mature milk) were collected. Carotenoid levels were analysed by HPLC. Carotenoid levels in breast milk changed as lactation progressed (P < 0·001). ß-Carotene was the primary carotenoid in colostrum. Lutein accounted for approximately 50 % of total carotenoids in transitional milk, mature milk and cord blood. Positive correlations were observed between five carotenoids in umbilical cord blood and maternal blood (P all < 0·001). ß-Carotene levels were also correlated between maternal plasma and three stages of breast milk (r = 0·605, P < 0·001; r = 0·456, P = 0·011, r = 0·446; P = 0·013, respectively). Dietary carotenoid intakes of lactating mothers also differed across lactation stages, although no correlation with breast milk concentrations was found. These findings suggest the importance of exploring the transport mechanism of carotenoids between mothers and infants and help guide the development of formulas for Chinese infants as well as the nutritional diets of lactating mothers.
Assuntos
Carotenoides , Leite Humano , Feminino , Lactente , Recém-Nascido , Humanos , Leite Humano/química , Sangue Fetal/química , beta Caroteno , Lactação , Estudos Longitudinais , China , Ingestão de AlimentosRESUMO
AIM: This study aimed to investigate how blood lipids are associated with diabetes among older Chinese adults. METHODS: 3,268,928 older Chinese adults without known diabetes were included. Logistic regression and restricted cubic spline (RCS) models were conducted to study associations between blood lipids (total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) and diabetes. RESULTS: 202,832 diabetes cases were included. Compared with the lowest quintiles, TC, TG, and LDL-C in the highest quintiles showed a higher diabetes prevalence risk and HDL-C presented a lower risk in multivariate-adjusted logistic regression models. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for the highest quintiles of TC, TG, and HDL-C were 1.39 (1.37-1.41), 2.56 (2.52-2.60), and 0.73 (0.72-0.74), respectively. For LDL-C, 3-5% lower risk was found in the second and third quintiles, and 4-23% higher risk was found in the fourth and fifth quintiles. RCS curves showed a non-linear relationship between each blood lipid parameters and diabetes (P-non-linear < 0.001). TG and HDL-C curves presented monotonically increasing and L-shaped patterns, respectively, whereas TC and LDL-C curves exhibited a J-shaped pattern. When TC < 4.04 mmol/L or LDL-C < 2.33 mmol/L, ORs of diabetes increased with the decrease of corresponding indexes. However, after excluding participants with lower LDL-C, the J-shaped association with TC disappeared. CONCLUSIONS: This study demonstrates non-linear associations between lipids and diabetes. Low cholesterol levels are associated with a high risk of diabetes. The cholesterol paradox should be considered during lipid-lowering treatments.
Assuntos
HDL-Colesterol , LDL-Colesterol , Diabetes Mellitus , Registros Eletrônicos de Saúde , Triglicerídeos , Humanos , Idoso , Masculino , Feminino , Estudos Transversais , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Triglicerídeos/sangue , Lipídeos/sangue , China/epidemiologia , Fatores de Risco , Idoso de 80 Anos ou mais , Razão de Chances , Modelos Logísticos , Colesterol/sangue , População do Leste AsiáticoRESUMO
BACKGROUND: Evidence on the association between multimorbidity and cognitive impairment in Chinese older population is limited. In addition, whether a healthy lifestyle can protect cognitive function in multimorbid older population remains unknown. METHODS: A total of 6116 participants aged ≥ 65 years from the Chinese Longitudinal Healthy Longevity Survey were followed up repeatedly. The number of coexisting chronic diseases was used for assessing multimorbidity and cardiometabolic multimorbidity. Three lifestyle statuses (unhealthy, intermediate, and healthy) were defined based on a lifestyle score covering smoking, alcohol drinking, body mass index, outdoor activities, and dietary pattern. Cognitive impairment was defined as the Mini-Mental State Examination score < 24. A modified Poisson regression model with robust error variance was used to assess the associations between multimorbidity, healthy lifestyle, and cognitive impairment. RESULTS: During a median follow-up period of 5.8 years, 1621 incident cases of cognitive impairment were identified. The relative risk (RR) of cognitive impairment associated with heavy multimorbidity burden (≥ 3 conditions) was 1.39 (95% confidence interval: 1.22-1.59). This association declined with age, with RRs being 3.08 (1.78-5.31), 1.40 (1.04-1.87), and 1.19 (1.01-1.40) in subjects aged < 70 years, ≥ 70 and < 80 years, and ≥ 80 years, respectively (P for interaction = 0.001). Compared to unhealthy lifestyle, a healthy lifestyle was related to an approximately 40% reduced risk of cognitive impairment regardless of multimorbidity burden. Among the 5 lifestyle factors assessed, daily outdoor activities and a healthy dietary pattern showed convincing protective effects on cognitive function. CONCLUSIONS: The relationship between multimorbidity and cognitive impairment is age-dependent but remains significant in the population aged 80 years or older. A healthy lifestyle may protect cognitive function regardless of the multimorbidity burden. These findings highlight the importance of targeting individuals with heavy multimorbidity burden and promoting a heathy lifestyle to prevent cognitive impairment in Chinese older population.
Assuntos
Disfunção Cognitiva , Multimorbidade , Humanos , Idoso , Estudos Longitudinais , Estudos de Coortes , Estilo de Vida Saudável , Disfunção Cognitiva/epidemiologia , China/epidemiologiaRESUMO
BACKGROUND: Biological age (BA) has been recognized as a more accurate indicator of aging than chronological age (CA). However, the current limitations include: insufficient attention to the incompleteness of medical data for constructing BA; Lack of machine learning-based BA (ML-BA) on the Chinese population; Neglect of the influence of model overfitting degree on the stability of the association results. METHODS AND RESULTS: Based on the medical examination data of the Chinese population (45-90 years), we first evaluated the most suitable missing interpolation method, then constructed 14 ML-BAs based on biomarkers, and finally explored the associations between ML-BAs and health statuses (healthy risk indicators and disease). We found that round-robin linear regression interpolation performed best, while AutoEncoder showed the highest interpolation stability. We further illustrated the potential overfitting problem in ML-BAs, which affected the stability of ML-Bas' associations with health statuses. We then proposed a composite ML-BA based on the Stacking method with a simple meta-model (STK-BA), which overcame the overfitting problem, and associated more strongly with CA (r = 0.66, P < 0.001), healthy risk indicators, disease counts, and six types of disease. CONCLUSION: We provided an improved aging measurement method for middle-aged and elderly groups in China, which can more stably capture aging characteristics other than CA, supporting the emerging application potential of machine learning in aging research.
Assuntos
Envelhecimento , Modelos Biológicos , Idoso , Biomarcadores , Mineração de Dados , Humanos , Aprendizado de Máquina , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Small interfering RNA (siRNA) is utilized as a potent agent for cancer therapy through regulating the expression of genes associated with tumors. While the widely application of siRNAs in cancer treatment is severely limited by their insufficient biological stability and its poor ability to penetrate cell membranes. Targeted delivery systems hold great promise to selectively deliver loaded drug to tumor site and reduce toxic side effect. However, the elevated tumor interstitial fluid pressure and efficient cytoplasmic release are still two significant obstacles to siRNA delivery. Co-delivery of chemotherapeutic drugs and siRNA represents a potential strategy which may achieve synergistic anticancer effect. Herein, we designed and synthesized a dual pH-responsive peptide (DPRP), which includes three units, a cell-penetrating domain (polyarginine), a polyanionic shielding domain (ehG)n, and an imine linkage between them. Based on the DPRP surface modification, we developed a pH-responsive liposomal system for co-delivering polo-like kinase-1 (PLK-1) specific siRNA and anticancer agent docetaxel (DTX), D-Lsi/DTX, to synergistically exhibit anti-tumor effect. RESULTS: In contrast to the results at the physiological pH (7.4), D-Lsi/DTX lead to the enhanced penetration into tumor spheroid, the facilitated cellular uptake, the promoted escape from endosomes/lysosomes, the improved distribution into cytoplasm, and the increased cellular apoptosis under mildly acidic condition (pH 6.5). Moreover, both in vitro and in vivo study indicated that D-Lsi/DTX had a therapeutic advantage over other control liposomes. We provided clear evidence that liposomal system co-delivering siPLK-1 and DTX could significantly downregulate expression of PLK-1 and inhibit tumor growth without detectable toxic side effect, compared with siPLK-1-loaded liposomes, DTX-loaded liposomes, and the combinatorial administration. CONCLUSION: These results demonstrate great potential of the combined chemo/gene therapy based on the multistage pH-responsive codelivery liposomal platform for synergistic tumor treatment.
Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/química , Docetaxel/farmacologia , Concentração de Íons de Hidrogênio , Lipossomos/química , Neoplasias/tratamento farmacológico , RNA Interferente PequenoRESUMO
The difference of nutrient composition between organic eggs and conventional eggs has always been a concern of people. In this study, 1H nuclear magnetic resonance (NMR) technique combined with multivariate statistical analyses was conducted to identify the metabolite different in egg yolk and egg white in order to reveal the nutritional components information between organic and conventional eggs. The results showed that the nutrient content and composition characteristics were different between organic and conventional eggs, among which the content of glucose, putrescine, amino acids and their derivatives were found higher in the organic eggs yolk, while phospholipids were demonstrated higher in conventional eggs yolk. Organic acid, alcohol, amine, choline and amino acids were higher in conventional eggs white, but glucose and lactate in organic egg were higher. Our study demonstrated that there are more nutritive components and higher nutritional value in organic eggs than conventional eggs, especially for the growth and development of infants and young children, and conventional eggs have more advantages in promoting lipid metabolism, preventing fatty liver, and reducing serum cholesterol. Eggs have important nutritional value to human body, and these two kinds of eggs can be selected according to the actual nutrient needs.
Assuntos
Galinhas , Ovos , Aminoácidos/metabolismo , Animais , Galinhas/metabolismo , Criança , Pré-Escolar , Análise Discriminante , Gema de Ovo/química , Ovos/análise , Ácidos Graxos/análise , Glucose/metabolismo , Humanos , Metabolômica , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Reactive oxygen species (ROS) derived from aberrant tumor metabolism could contribute to tumor invasion and metastasis. NAD(P)HX Epimerase (NAXE), an epimerase that allows the repair of damaged forms of antioxidant NADPH, is a potential cellular ROS scavenger and its role in tumor development is still elusive. Here, we found that NAXE is significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. NAXE downregulation is associated with poor clinicopathological characteristics and is an independent risk factor for overall and disease-free survival of HCC patients after liver resection. In addition, low NAXE expression could identify worse prognosis of HCC patients before vascular invasion or in early stages of disease. In particularly, low NAXE expression in HCC is markedly associated with microvascular invasion (MVI) and its combination with MVI predicts poorer prognosis of HCC patients after liver resection. Furthermore, in vitro and in vivo experiments both showed that knockdown of NAXE expression in HCC cells promoted migration, invasion, and metastasis by inducing epithelial-mesenchymal transition (EMT), whereas NAXE overexpression causes the opposite effects. Mechanistically, low NAXE expression reduced NADPH levels and further caused ROS level increase and hypoxia-inducible factor-1α (HIF-1α) activation, thereby promoting invasion and metastasis of HCC by facilitating EMT. What is more, the tumor-promoting effect of NAXE knockdown in HCC xenograft can be abolished by giving mice N-acetyl-l-cysteine (NAC) in drinking water. Taken together, our findings uncovered a tumor suppressor role for NAXE in HCC by scavenging excessive ROS and inhibiting tumor-promoting signaling pathways, suggesting a new strategy for HCC therapy by targeting redox signaling.
Assuntos
Carcinoma Hepatocelular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/metabolismo , Racemases e Epimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Análise de Variância , Animais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Movimento Celular , Progressão da Doença , Intervalo Livre de Doença , Regulação para Baixo , Transição Epitelial-Mesenquimal , Feminino , Sequestradores de Radicais Livres/farmacologia , Xenoenxertos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Camundongos , Pessoa de Meia-Idade , NADP/metabolismo , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Transplante de Neoplasias , Oxirredução , Racemases e Epimerases/genética , Fatores de RiscoRESUMO
Carotenoids are increasingly being implicated to have an important role in brain and eye development. This study aimed to quantify the content and profile of carotenoids in human breast milk, maternal plasma and neonatal umbilical cord plasma in Chengdu, an urban area in Southwest China. In this study, fifty-four healthy mothers were enrolled. Maternal blood, umbilical cord blood, colostrum, transitional milk and mature milk were collected. Concentrations of carotenoids (lutein, zeaxanthin, ß-cryptoxanthin, ß-carotene and lycopene) were analysed by HPLC. We found that carotenoid concentrations decreased from colostrum to mature milk. Hydrocarbon carotenoids with weaker polarity decreased more than the polar carotenoids. Lycopene concentrations dropped by 99 %, ß-carotene by 92 %, ß-cryptoxanthin by 83 %, lutein by 32 % and zeaxanthin by 22 %. Lycopene and ß-carotene accounted for 70 % of the total carotenoids in colostrum, and lutein predominated amongst carotenoids in transitional milk and mature milk (51-55 %). Carotenoid concentrations in maternal plasma were much higher than that in cord plasma. Lutein predominated in cord plasma. The concentrations of all carotenoids in maternal plasma were correlated with those of cord plasma and human milk. These results are consistent with selective transport mechanisms in the mammary gland related to the polarity of carotenoids, and each carotenoid has its own implications, which may have different priorities in the early life development of infants. These findings may help guide dietary recommendations for carotenoid inclusion in infant formulas.
Assuntos
Carotenoides , Sangue Fetal/química , Leite Humano , beta-Criptoxantina , Carotenoides/análise , China , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Luteína , Licopeno , Leite Humano/química , Gravidez , Zeaxantinas , beta CarotenoRESUMO
OBJECTIVE: To investigate the fatty acid composition in breast milk at different lactation stages in six representative cities of China. METHODS: From January 2018 to December 2019, milk sampling of 690 healthy lactating mothers(full-term) in 5 lactation periods of 0-5 days, 10-14 days, 40-45 days, 200-240 days and 300-400 days was collected from 6 representative regions in China, with 23 cases of breast milk received in each lactation stage in each city. Mix it into one mixture, and make a total of 30 mixes. Determination of fatty acids in breast milk was conducted by gas chromatography-flame ionization detector. RESULTS: The contents of total fatty acids(TFA), saturated fatty acids(SFA), monounsaturated fatty acids(MUFA) and polyunsaturated fatty acids(PUFA) in breast milk increased with the progress of lactation and reached a relatively stable level after reaching a peak at 40-45 days. However, the composition ratio of SFA, MUFA and PUFA in TFA remained relatively stable from 0 to 400 days. The ratio of arachidonic to docosahexaenoic(AA/DHA) in breast milk from 0 to 400 days in the six cities ranged from 1.14 to 1.55, and there was no obvious trend of change in the whole lactation stage. The ratio of linoleic acid to alpha-linolenic acid(LA/ALA) in Chinese breast milk ranged from 3.84 to 18.94, showing significant regional variation. CONCLUSION: The content and composition of fatty acids in breast milk of six cities in China vary to a certain extent and show a dynamic change process with the passage of time of lactation.
Assuntos
Lactação , Leite Humano , China , Cidades , Ácidos Graxos , Feminino , HumanosRESUMO
OBJECTIVE: The study aimed to investigate the contents and isomer composition of vitamin E in mature milk in different regions of China. METHODS: Simultaneously recruited 604 lactating mothers aged(29.58±3.43) from Shanghai, Guangzhou, Tianjin, Chengdu, Lanzhou and Changchun cities. They were mainly primiparas with good education background. A total number of 604 mature milk samples was collected. The contents of α-, γ-, δ-tocopherols and the stereoisomers of α-tocopherol were determined by high performance liquid chromatography(HPLC). RESULTS: The M(P25, P75) concentrations of α-tocopherol, RRR-α-tocopherol, γ-tocopherol and δ-tocopherol in Chinese mature milk were 3.16(2.29, 4.16)mg/L, 2.57(1.77, 3.48)mg/L, 0.89(0.58, 1.27)mg/L and 0.17(0.09, 0.27)mg/L, respectively. The total α-TE level was 3.09(2.22, 4.10)mg/L with statistically regional differences(P<0.001). RRR-α-tocopherol was the predominated stereoisomers of α-tocopherol, accounting for 83.17%(76.36%, 88.43%). The proportion of RRR in Tianjin mature milk was significantly lower than that in Lanzhou(77.11% vs. 86.16%, P<0.001) while breast milk samples from other regions had similar RRR-α-tocopherol proportions(82.82%-85.39%). CONCLUSION: Vitamin E content in mature milk was mainly composed of α-tocopherol. Even though the contents of tocopherols have large regional differences, RRR-α-tocopherol was predominated form in all breast milk samples. It is suggested that RRR-α-tocopherol was the main active form of vitamin E in the early stage of life.
Assuntos
Leite Humano , Vitamina E , China , Feminino , Humanos , Lactação , Leite Humano/química , Estereoisomerismo , alfa-Tocoferol/análiseRESUMO
Human milk fat is specially tailored to supply the developing infant with adequate and balanced nutrients. The present study aimed to quantify the composition of fatty acids, tocopherols and carotenoids in human milk, with special emphasis on the lactational changes. Colostrum, transitional and mature milk samples were collected longitudinally from the same forty-two healthy, well-nourished Chinese mothers. Fatty acids were quantified by GC with carotenoids (carotenes and xanthophylls) and tocopherols (α-, γ-tocopherol) determined by HPLC. Total fatty acid (TFA) content increased from 15·09 g/l in colostrum to 32·57 g/l in mature milk with the percentages of DHA and arachidonic acid (ARA) decreased. The ratio of n-6:n-3 PUFA and ARA:DHA remained constant during lactation at about 11:1 and 1·3:1, respectively. Both α-tocopherol and γ-tocopherol decreased over lactation with the ratio of α-:γ-tocopherol declined significantly from 7·21:1 to 4·21:1 (P < 0·001). Carotenoids all dropped from colostrum to mature milk as the less polar carotenes dropped by 88·67 %, while xanthophylls only dropped by 35·92 %. Lutein was predominated in both transitional and mature milk carotenoids (51·64-52·49 %), while colostrum carotenoids were mainly composed of lycopene (32·83 %) and ß-carotene (30·78 %). The concentrations of tocopherols and xanthophylls but not carotenes were positively associated with TFA content in milk. These results suggested that colostrum and mature milk contained divergent lipid profiles and selective transfer mechanisms related to polarity might be involved. The present outcomes provide new insights for future breast-feeding studies, which also add in scientific evidences for the design of both initial and follow-on infant formulas.
Assuntos
Antioxidantes/metabolismo , Ácidos Graxos/química , Lactação/fisiologia , Leite Humano/química , Adulto , Antioxidantes/química , Povo Asiático , China , Ácidos Graxos/metabolismo , Feminino , Humanos , Adulto JovemRESUMO
Heart development protein with EGF-like domains 1 (HEG1) plays critical roles in embryo development and angiogenesis, which are closely related to tumor progression. However, the role of HEG1 in hepatocellular carcinoma (HCC) remains unknown. In the present study, we explored the clinical significance, biological function and regulatory mechanisms of HEG1 in HCC and found that HEG1 is significantly up-regulated in HCC cell lines and primary tumor samples. Additionally, high HEG1 expression is correlated with aggressive clinicopathological features. Patients with high HEG1 expression had shorter overall survival (OS) and disease-free survival (DFS) than those with low HEG1 expression, which indicated that HEG1 is an independent factor for poor prognosis. Lentivirus-mediated HEG1 overexpression significantly promotes HCC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and promotes intrahepatic metastasis, lung metastasis and EMT in vivo Opposing results are observed when HEG1 is silenced. Mechanistically, HEG1 promotes ß-catenin expression and maintains its stability, leading to intracellular ß-catenin accumulation, ß-catenin nuclear translocation and Wnt signaling activation. Loss- and gain-of-function assays further confirmed that ß-catenin is essential for HEG1-mediated promotion of HCC invasion, metastasis and EMT. In conclusion, HEG1 indicates poor prognosis; plays important roles in HCC invasion, metastasis and EMT by activating Wnt/ß-catenin signaling; and can serve as a potentially valuable prognostic biomarker and therapeutic target for HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , beta Catenina/metabolismo , Adulto , Idoso , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Linhagem Celular Tumoral , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Via de Sinalização Wnt , beta Catenina/genéticaRESUMO
BACKGROUND & AIMS: BCAT1 initiates the catabolism of branched-chain amino acids. Here, we investigated the function of BCAT1 and its transcriptional regulatory mechanism in hepatocellular carcinoma (HCC). METHODS: RNASeq was used to evaluate BCAT1 mRNA levels in HCC and normal matched specimens. After the exogenous expression of BCAT1 in BEL-7404 cells and the suppression of endogenous BCAT1 expression with shRNA in HepG2 cells, the cell proliferation, clone-forming ability and cell-cycle changes were measured with MTT assay, colony-forming assay and flow cytometry respectively. A xenograft model was used to investigate the effect of BCAT1 on cancer growth in vivo. Chromatin immunoprecipitation and luciferase reporter technologies were used to confirm the transcriptional regulation of the BCAT1 gene by MYC. The expression of the BCAT1 and MYC proteins in 122 HCC tissues was determined with an immunohistochemical analysis. RESULTS: BCAT1 mRNA was clearly increased in HCC tissues and hepatomas. The ectopic expression of BCAT1 in BEL-7404 cells enhanced their proliferation, clone formation, tumourigenic properties, S-G2 /M phase transition and chemoresistance to cisplatin. The suppression of BCAT1 expression in HepG2 cells significantly inhibited their proliferation, clone formation, and S-G2 /M phase transition and caused their chemosensitization to cisplatin. MYC affected the transcriptional regulation of BCAT1. Clinical data showed that BCAT1 expression correlated with a significantly poorer prognosis. CONCLUSION: BCAT1 plays a pathogenic role in HCC by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT1. BCAT1 expression has prognostic significance for the survival of patients with HCC.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/genética , Transaminases/genética , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , China , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , RNA Interferente Pequeno/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The therapeutic potential of baicalein against hepatoma cells was evaluated in vitro and in vivo. In cell viability assays, baicalein showed significant cytotoxicity against the hepatocellular carcinoma cell lines H22, Bel-7404, and Hep G2 and moderate cytotoxicity against immortalized human hepatocytes. Baicalein induced G0/G1-phase arrest in hepatocellular carcinoma cells, inhibited AKT, and promoted the degradation of ß-catenin and cyclin D1 without activation of GSK-3ß. Furthermore, baicalein significantly inhibited H22 xenograft tumor growth without causing obvious adverse effects on weight or liver and spleen weight indexes in ICR mice. Immunohistochemical analysis showed that the inhibition of tumor growth in baicalein-treated mice was associated with decreased AKT, ß-catenin, and cyclin D1 expression ex vivo. Our data indicate that baicalein might regulate cyclin D1 transcription via a ß-catenin-dependent mechanism, leading to cell cycle arrest at G0/G1 phase and impaired cancer cell proliferation. These results suggest that baicalein is a potential candidate for the treatment of hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/patologia , Flavanonas/farmacologia , Neoplasias Hepáticas/patologia , Animais , Carcinoma Hepatocelular/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos Endogâmicos ICR , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismoRESUMO
The Bayer red mud (RM) and phosphogypsum (PG) accumulation have caused significant environmental contamination. However, practical and effective resource utilization technologies are still lacking currently. This work aims to develop ferric sulfoaluminate cement (FSAC) employing low-cost materials including Bayer red mud, phosphogypsum, and other materials. This method effectively improves the utilization rate of Bayer red mud and phosphogypsum. Under the premise of ensuring the performance of FSAC, the utilization rate of solid waste can reach up to 48.56%. The effects of different red mud dosages on cement mineral formation, workability, and mechanical properties are investigated. Then, untreated phosphogypsum is adopted as a retarder for FSAC, and the hydration process, working properties, mechanical properties, types of hydration products, and morphology of FSAC are explored. The results suggest that the crystal transformation of Ye'elemite C 4 A 3 S ¯ is promoted with the increase of Bayer red mud content. Cubic crystal system Ye'elemite C 4 A 3 S ¯ - c with higher hydration activity is generated, which increases the early strength of cement but greatly reduces the setting time, hindering the later strength growth. Untreated phosphogypsum can effectively delay the early hydration process of FSAC, prolong the setting time of cement, and increase the strength of FSAC in the later stage. When the dosage of Bayer red mud and phosphogypsum is 17.64% and 9.21%, respectively, with phosphogypsum dosage of 20%, the prepared FSAC has satisfactory mechanical properties, and the 3-day and 90-day compressive strengths are 34.6 MPa and 57.1 MPa, respectively. In addition, the study of heavy metal leaching indicates that the FSAC prepared by Bayer red mud, phosphogypsum, and other raw materials will generate no environment pollution, and the solidification of heavy metal elements in the cement slurry is superior.
Assuntos
Sulfato de Cálcio , Materiais de Construção , Fósforo , Sulfato de Cálcio/química , Fósforo/químicaRESUMO
Alcohol consumption and metabolic syndrome(MetS), both prevalent in the general population, frequently co-occur. They are recognized as significant contributors to liver dysfunction, yet their combined effect is often challenging to delineate. This study delves into the compounding influence of alcohol consumption and metabolic disorder on liver dysfunction within an elderly demographic in Zhejiang Province, China. Our findings spotlight a heightened risk of liver dysfunction among females, younger individuals, rural dwellers, those with minimal educational attainment, single individuals, and those diagnosed with MetS. We also discerned a positive correlation correlation between the number of MetS components and the propensity for liver dysfunction. Furthermore, the risk of liver dysfunction escalated in tandem with the frequency of alcohol consumption. Interestingly, a prolonged abstinence period (≥ 5 years) seemed to mitigate this risk. Our research underscores the significance of refraining from excessive alcohol consumption, embracing a healthy lifestyle, and managing MetS components-especially triglyceride levels-for effective prevention of liver dysfunction.
RESUMO
The Electrolytic Manganese Residue (EMR) is a by-product of the electrolytic manganese metal (EMM) industry, containing high concentrations of potential pollutants such as NH4+-N and soluble Mn2+. These components pose a serious threat to the ecological environment. To explore accurate, efficient, and harmless treatment methods for EMR, this study proposes a low-temperature thermochemical approach. The orthogonal experiment design investigates the effects of reaction temperature, reaction time, quicklime (CaO), sodium carbonate (Na2CO3), sodium phosphate (Na3PO4) (Reviewer #3), and water consumption on manganese solidified and ammonia removal from EMR. The results indicate that optimal conditions are a reaction temperature of 60 â (Reviewer #3) and a reaction time of 10 min. CaO precipitates Mn2+ as manganese hydroxide (Mn(OH)2) (Reviewer #3), achieving effective manganese solidified and ammonia removal. The addition of Na2CO3 causes Mn2+ to form manganesecarbonate (MnCO3) (Reviewer #3)precipitate, while Na3PO4 makes Mn2+ form Manganese phosphate trihydrate (Mn3(PO4)2·3H2O) (Reviewer #3). Increased water consumption enhances the interaction adequacy between ions. Under optimal conditions (CaO 10%, Na2CO3 1%, Na3PO4 0.5%, and 80% water consumption), the removal rate of ammonium ions reaches 98.5%, and the solidification rate of soluble Mn2+ is 99.9%. The order of influence on ammonium ion removal is CaO > water consumption > Na3PO4 > Na2CO3. Therefore, this study provides a new method for low-cost process disposal and efficient harmless treatment of EMR (Reviewer #3).
Assuntos
Manganês , Manganês/química , Temperatura , Amônia/química , EletróliseRESUMO
Single nutrient likes polyphenol or dietary fiber have been exhaustively investigated to validate their positive intervention in health or disease. Meanwhile, the common interaction of inner systems with the nutrient complex has not been well elucidated, which raises the scientific issue of the modulatory effect of the nutrient complex on immunity. The representative prebiotics of epigallocatechin-3-gallate (EGCG), ginseng extract, and polydextrose (PDX) were selected on behalf of the classification of polyphenol, flavone or polysaccharides, and dietary fiber to generally cover the daily food intake in this study to explore their intervention in inflammation and macrophage polarization. The intervention of selected nutrients on inflammation and macrophage polarization has been evaluated against macrophages to unveil their comprehensive effects. The synergistic effect of selected nutrients was demonstrated by inhibiting M1 macrophage polarization and the promotion of M2 macrophage polarization. Then, the nutrient formula was set up to verify the intervention effect, and the results revealed the significant inhibition of cell inflammation and the effect on cell proliferation through promoting the cell cycle in the G2 phase. The nutrient complex could inhibit M1 macrophage polarization to inhibit M1-mediated inflammation and promote M2 macrophages for anti-inflammatory effect and enhance cell phagocytosis. Moreover, the varied intervention effects of the nutrient complex with different formulas could be summarized. In general, the formula containing EGCG, ginseng extract, and PDX was demonstrated to possess an enhanced immunomodulatory effect on cell inflammation and macrophage polarization, which could potentially inspire the investigation of complex nutrients in health and diseases.