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1.
Mol Nutr Food Res ; 68(9): e2300314, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38639304

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Alimento Processado , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Dieta , Manipulação de Alimentos , Fatores de Risco , Biobanco do Reino Unido , Reino Unido/epidemiologia
2.
Proc Natl Acad Sci U S A ; 121(4): e2317058121, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38232281

RESUMO

Integration of methanogenic archaea with photocatalysts presents a sustainable solution for solar-driven methanogenesis. However, maximizing CH4 conversion efficiency remains challenging due to the intrinsic energy conservation and strictly restricted substrates of methanogenic archaea. Here, we report a solar-driven biotic-abiotic hybrid (biohybrid) system by incorporating cadmium sulfide (CdS) nanoparticles with a rationally designed methanogenic archaeon Methanosarcina acetivorans C2A, in which the glucose synergist protein and glucose kinase, an energy-efficient route for glucose transport and phosphorylation from Zymomonas mobilis, were implemented to facilitate nonnative substrate glucose for methanogenesis. We demonstrate that the photo-excited electrons facilitate membrane-bound electron transport chain, thereby augmenting the Na+ and H+ ion gradients across membrane to enhance adenosine triphosphate (ATP) synthesis. Additionally, this biohybrid system promotes the metabolism of pyruvate to acetyl coenzyme A (AcCoA) and inhibits the flow of AcCoA to the tricarboxylic acid (TCA) cycle, resulting in a 1.26-fold augmentation in CH4 production from glucose-derived carbon. Our results provide a unique strategy for enhancing methanogenesis through rational biohybrid design and reprogramming, which gives a promising avenue for sustainably manufacturing value-added chemicals.


Assuntos
Trifosfato de Adenosina , Metano , Metano/metabolismo , Transporte de Elétrons , Trifosfato de Adenosina/metabolismo , Metabolismo Energético , Transporte Biológico , Methanosarcina/metabolismo
3.
JAMA Netw Open ; 6(7): e2323584, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37450300

RESUMO

Importance: Adherence to a healthy lifestyle is associated with lower risks of adverse outcomes. However, trends in multiple lifestyle factors and overall healthy lifestyle status among US adults in recent years are unknown. Objective: To examine trends in multiple lifestyle factors and overall healthy lifestyle among US adults. Design, Setting, and Participants: This serial cross-sectional study used nationally representative data from 10 National Health and Nutrition Examination Survey (NHANES) cycles (nine 2-year cycles from 1999 to 2016 and 1 combined cycle from 2017 to March 2020) among adults 20 years or older. Data were analyzed from December 10, 2021, to January 11, 2023. Exposure: Survey cycle. Main Outcomes and Measures: Five healthy lifestyle factors: never smoking, moderate or lighter alcohol consumption (for women: ≤7 drinks/wk; for men: ≤14 drinks/wk), healthy diet (Healthy Eating Index-2015 scores ≥60.0), sufficient physical activity (≥150 min/wk of equivalent moderate physical activity), and healthy weight (body mass index [calculated as weight in kilograms divided by height in meters squared] 18.5-24.9). Results: A total of 47 852 adults were included in this study. The weighted mean [SE] age was 47.3 [0.2] years; 24 539 (weighted proportion, 51.5%) were women. From the 1999-2000 cycle to the 2017 to March 2020 cycle, the estimated prevalence of the 5 lifestyle factors showed divergent trends, with increasing prevalence of never smoking (from 49.4% [95% CI, 46.4%-52.4%] to 57.7% [95% CI, 55.5%-59.9%]; difference, 8.2% [95% CI, 4.5%-12.0%]), healthy diet (from 19.3% [95% CI, 16.0%-22.6%] to 24.5% [95% CI, 21.5%-27.5%]; difference, 5.2% [95% CI, 0.8%-9.7%]), and sufficient physical activity (from 55.7% [95% CI, 51.8%-59.6%] to 69.1% [95% CI, 67.2%-71.1%]; difference, 13.4% [95% CI, 9.0%-17.8%]), while prevalence of healthy weight decreased from 33.1% (95% CI, 30.5%-35.6%) to 24.6% (95% CI, 22.6%-26.7%; difference, -8.4% [95% CI, -11.8% to -5.1%]) (all P < .001 for trend). Meanwhile, there was no significant trend in moderate or lighter alcohol consumption. Overall, the estimated prevalence of at least 4 healthy lifestyle factors increased from 15.7% (95% CI, 12.8%-18.7%) to 20.3% (95% CI, 17.8%-22.7%; difference, 4.5% [95% CI, 0.7%-8.4%]; P < .001 for trend). Disparities in healthy lifestyle were widened by age group, with little improvement among adults 65 years and older (difference, 0.04% [95% CI, -4.28% to 4.35%]). There were persistent disparities in healthy lifestyle by race and ethnicity, educational level, and income level. Conclusions and Relevance: The findings of this cross-sectional study of NHANES data over a 22-year period suggest diverse change patterns across 5 healthy lifestyle factors and a modest improvement in overall lifestyle existed among US adults, with worsening or persistent disparities in lifestyle.


Assuntos
Dieta Saudável , Dieta , Masculino , Adulto , Humanos , Feminino , Lactente , Idoso , Inquéritos Nutricionais , Autorrelato , Estudos Transversais
4.
Biochem Genet ; 61(6): 2481-2495, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37118619

RESUMO

Gambogic acid (GA) has been observed to effectively impede the progression of numerous types of cancers. In this study, we investigated the effects of miR-1275 and Secreted Protein Acidic and Cysteine Rich (SPARC) on GA in gastric cancer (GC). miR-1275 and SPARC expression were determined in GC cell lines and tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between miR-1275 and SPARC expression was ascertained using Pearson's correlation coefficient. Cell proliferation was assessed using the cell counting kit-8 (CCK-8) assay. The Transwell assay was conducted to examine cell migration. A dual-luciferase reporter assay was used to verify the regulatory relationship between miR-1275 and SPARC. The levels of SPARC, Bcl-2, and Bax proteins were estimated using western blotting. To verify the effects of GA on the growth of GC cells in vivo, a tumorigenesis experiment was performed in nude mice. GA suppressed GC cell viability and migration, facilitated apoptosis, and inhibited tumor growth in vivo and in vitro. Low levels of miR-1275 been observed in GC cell lines and tissues. GA-treated GC cells manifested high miR-1275 levels. In functional experiments, miR-1275 enhanced the influence of GA on cell apoptosis, migration, and proliferation. Furthermore, GA treatment suppressed SPARC upregulation in GC cell lines and tissues. Pearson's correlation coefficient revealed that miR-1275 expression negatively correlated with SPARC expression. Mechanistically, miR-1275 promoted growth inhibition in GA-treated GC cells by targeting SPARC. Our study indicates that miR-1275 enhances the suppressive effect of GA on GC progression by inhibiting SPARC expression. Through this study, we contribute to the knowledge of a new mechanism by which GA suppresses GC progression.


Assuntos
MicroRNAs , Neoplasias Gástricas , Animais , Camundongos , Neoplasias Gástricas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Regulação Neoplásica da Expressão Gênica , Movimento Celular
5.
Mayo Clin Proc ; 98(1): 60-74, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36603958

RESUMO

OBJECTIVE: To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes. PATIENTS AND METHODS: Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020. RESULTS: A total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses. CONCLUSION: The international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Humanos , Estados Unidos/epidemiologia , Fatores de Risco , Estudos Prospectivos , Inquéritos Nutricionais , Estilo de Vida Saudável , Diabetes Mellitus/epidemiologia
7.
Diabetologia ; 65(12): 2044-2055, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36102938

RESUMO

AIMS/HYPOTHESIS: Cancer has contributed to an increasing proportion of diabetes-related deaths, while lifestyle management is the cornerstone of both diabetes care and cancer prevention. We aimed to evaluate the associations of combined healthy lifestyles with total and site-specific cancer risks among individuals with diabetes. METHODS: We included 92,239 individuals with diabetes but without cancer at baseline from five population-based cohorts in the USA (National Health and Nutrition Examination Survey and National Institutes of Health [NIH]-AARP Diet and Health Study), the UK (UK Biobank study) and China (Dongfeng-Tongji cohort and Kailuan study). Healthy lifestyle scores (range 0-5) were constructed based on current nonsmoking, low-to-moderate alcohol drinking, adequate physical activity, healthy diet and optimal bodyweight. Cox regressions were used to calculate HRs for cancer morbidity and mortality, adjusting for sociodemographic, medical and diabetes-related factors. RESULTS: During 376,354 person-years of follow-up from UK Biobank and the two Chinese cohorts, 3229 incident cancer cases were documented, and 6682 cancer deaths were documented during 1,089,987 person-years of follow-up in the five cohorts. The pooled multivariable-adjusted HRs (95% CIs) comparing participants with 4-5 vs 0-1 healthy lifestyle factors were 0.73 (0.61, 0.88) for incident cancer and 0.55 (0.46, 0.67) for cancer mortality, and ranged between 0.41 and 0.63 for oesophagus, lung, liver, colorectum, breast and kidney cancers. Findings remained consistent across different cohorts and subgroups. CONCLUSIONS/INTERPRETATION: This international cohort study found that adherence to combined healthy lifestyles was associated with lower risks of total cancer morbidity and mortality as well as several subtypes (oesophagus, lung, liver, colorectum, breast and kidney cancers) among individuals with diabetes.


Assuntos
Diabetes Mellitus , Neoplasias Renais , Humanos , Estudos de Coortes , Inquéritos Nutricionais , Estudos Prospectivos , Estilo de Vida Saudável , Morbidade , China/epidemiologia , Reino Unido/epidemiologia , Fatores de Risco
8.
Front Oncol ; 12: 940220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033510

RESUMO

Necroptosis is closely related to the occurrence and development of tumors, including glioma. A growing number of studies indicate that targeting necroptosis could be an effective treatment strategy against cancer. Long non-coding RNA (lncRNA) is also believed to play a pivotal role in tumor epigenetics. Therefore, it is necessary to identify the functions of necroptosis-related lncRNAs in glioma. In this study, the transcriptome and clinical characteristic data of glioma patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were collected, and the differentially expressed necroptosis-related lncRNAs in TCGA that have an impact on overall survival (OS) were screened out to construct risk score (RS) formula, which was verified in CGGA. A nomogram was constructed to predict the prognosis of glioma patients based on clinical characteristics and RS. In addition, Gene Set Enrichment Analysis (GSEA) was used to analyze the main enrichment functions of these necroptosis-related lncRNAs and the immune microenvironment. A total of nine necroptosis-related lncRNAs have been identified to construct the RS formula, and the Kaplan-Meier (K-M) survival analysis showed significantly poorer outcomes in the high RS group in both TCGA and CGGA databases. Moreover, the receiver operating characteristic (ROC) curve shows that our prediction RS model has good predictability. Regarding the analysis of the immune microenvironment, significant differences were observed in immune function and immune checkpoint between the high RS group and the low RS group. In conclusion, we constructed a necroptosis-related lncRNA RS model that can effectively predict the prognosis of glioma patients and provided the theoretical basis and the potential therapeutic targets for immunotherapy against gliomas.

9.
Chin J Nat Med ; 20(4): 309-320, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35487601

RESUMO

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.


Assuntos
Interleucina-6 , Piridinolcarbamato , Animais , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/química , Dinoprostona , Interleucina-6/metabolismo , Glucosídeos Iridoides , Camundongos , Simulação de Acoplamento Molecular
10.
Cell Rep ; 39(2): 110670, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35417708

RESUMO

Factors released from glioma-associated microglia/macrophages (GAMs) play a crucial role in glioblastoma multiforme (GBM) progression. Here, we study the importance of CCL18, a cytokine expressed in human but not in rodent GAMs, as a modulator of glioma growth. Since CCL18 signaling could not be studied in classical mouse glioma models, we developed an approach by transplanting induced pluripotent stem cell-derived human microglia and human glioma cells into mouse brain slices depleted of their intrinsic microglia. We observe that CCL18 promotes glioma cell growth and invasion. Chemokine (C-C motif) receptor 8 (CCR8) is identified as a functional receptor for CCL18 on glioma cells, and ACP5 (acid phosphatase 5) is revealed as an important part of the downstream signaling cascade for mediating glioma growth. We conclude, based on the results from an in vitro, ex vivo humanized glioma model and an in vivo GBM model that microglia/macrophage-derived CCL18 promotes glioma growth.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Animais , Linhagem Celular Tumoral , Quimiocinas CC , Humanos , Macrófagos , Camundongos , Microglia , Receptores CCR8 , Fosfatase Ácida Resistente a Tartarato
11.
Eur Respir J ; 59(5)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34625481

RESUMO

BACKGROUND: Population studies show that the use of swimming pools is associated with the risk of asthma and allergic diseases among children. Our objective was to explore the associations between blood trihalomethane (THM) concentrations and asthma among US adolescents, and assess to what extent the association is modified by active tobacco smoke exposure. METHODS: We included 2359 adolescents aged 12-19 years with measured blood concentrations of chloroform (trichloromethane (TCM)), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (tribromomethane (TBM)) from the National Health and Nutrition Examination Survey 2005-2012. Logistic regression models were fitted to assess the odds ratios for the association of blood THM concentrations (three or four categories) with the risk of self-reported current and ever (lifetime) asthma. RESULTS: Blood DBCM concentrations were associated with a higher risk of ever asthma among all adolescents (OR 1.54 (95% CI 1.07-2.21), comparing the extreme exposure categories). The relationship was stronger among adolescents exposed to tobacco smoke (OR 3.96 (95% CI 1.89-8.30), comparing the extreme exposure categories). We also found positive relationships between blood brominated THM concentrations (sum of BDCM, DBCM and TBM) and risk of ever asthma and between blood DBCM and brominated THM concentrations and risk of current asthma among adolescents with tobacco smoke exposure. The relative excess risk of ever asthma due to the interaction between high blood DBCM and brominated THM concentrations and tobacco smoke exposure was 1.87 (95% CI 0.30-3.43) and 0.78 (95% CI 0.07-1.49), respectively. CONCLUSIONS: Exposure to THMs is associated with a higher risk of asthma in adolescents, particularly among those exposed to tobacco smoke.


Assuntos
Asma , Poluição por Fumaça de Tabaco , Poluentes Químicos da Água , Adolescente , Asma/epidemiologia , Criança , Estudos Transversais , Humanos , Inquéritos Nutricionais , Poluição por Fumaça de Tabaco/efeitos adversos , Trialometanos/análise , Poluentes Químicos da Água/análise
12.
Opt Lett ; 46(22): 5759-5762, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780455

RESUMO

Formaldehyde (FA) is one of the most common pollutants, which has tremendous harm to humans and environment. In this work, 4-amino-3-pentene-2-one (Fluoral-p) and SiO2 coated quantum dot (QD@SiO2) were combined to implement a new ratiometric fluorescence probe QD@SiO2-Fluoral-p for FA detection. In addition, by utilization of polyvinyl alcohol (PVA) and SiO2 microsphere (SM), a kind of PVA-SM microstructure was assembled with QD@SiO2-Fluoral-p to composite a signal enhanced sensing film. The QD@SiO2-Fluoral-p exhibited good response to 0-400 mg/L FA solution and an enhancement around 15 folds was realized after introducing PVA-SM. In both situations, the probe showed linear relationship to FA concentration (CFA), with detection limits of 14 and 0.5 mg/L, respectively. Also, the sensing film showed a good linear response to FA gas in the range of 0 to 2 ppm, with a detection limit 0.03 ppm. As a result, the PVA-SM enhanced ratiometric fluorescence probe features high sensitivity, low detection limit, good selectivity, as well as portable, which can serve as a useful tool for investigating FA in solution and gas at room temperature.

13.
Breast ; 59: 102-109, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34225090

RESUMO

BACKGROUND: The COVID-19 pandemic is a significant worldwide health crisis. Breast cancer patients with COVID-19 are fragile and require particular clinical care. This study aimed to identify the clinical characteristics of breast cancer patients with COVID-19 and the risks associated with anti-cancer treatment. METHODS: The medical records of breast cancer patients with laboratory-confirmed COVID-19 were collected among 9559 COVID-19 patients from seven designated hospitals from 13th January to 18th March 2020 in Hubei, China. Univariate and multivariate analyses were performed to assess risk factors for COVID-19 severity. RESULTS: Of the 45 breast cancer patients with COVID-19, 33 (73.3%) developed non-severe COVID-19, while 12 (26.7%) developed severe COVID-19, of which 3 (6.7%) patients died. The median age was 62 years, and 3 (6.7%) patients had stage IV breast cancer. Univariate analysis showed that age over 75 and the Eastern Cooperative Oncology Group (ECOG) score were associated with COVID-19 disease severity (P < 0.05). Multivariate analysis showed that patients who received chemotherapy within 7 days had a significantly higher risk for severe COVID-19 (logistic regression model: RR = 13.886, 95% CI 1.014-190.243, P = 0.049; Cox proportional hazards model: HR = 13.909, 95% CI 1.086-178.150, P = 0.043), with more pronounced neutropenia and higher LDH, CRP and procalcitonin levels than other patients (P < 0.05). CONCLUSIONS: In our breast cancer cohort, the severity of COVID-19 could be associated with baseline factors such as age over 75 and ECOG scores. Chemotherapy within 7 days before symptom onset could be a risk factor for severe COVID-19, reflected by neutropenia and elevated LDH, CRP and procalcitonin levels.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , COVID-19/diagnóstico , Neutropenia/etiologia , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Proteína C-Reativa , China/epidemiologia , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Pessoa de Meia-Idade , Neutropenia/epidemiologia , Pandemias , Pró-Calcitonina/sangue , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
14.
Exp Ther Med ; 22(3): 929, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34306198

RESUMO

Reversine (Rev) has been used for the treatment of a number of cancers. However, there have been no previous reports for the use of Rev for gastric cancer (GC). The aim of the present study was to investigate the effect of Rev on cell proliferation, migration, invasion and cell apoptosis in human GC cells and TTK expression. Cell Counting Kit-8 and colony formation were used to assess cell proliferation. Wound healing and Transwell assays were performed to examine cell migration and invasion, respectively. Cell apoptosis was measured using TUNEL staining and western blotting. Reverse transcription-quantitative PCR and western blotting were performed to determine TTK expression in AGS and NCI-N87 GC cells. Rev treatment inhibited the viability of the two GC cells lines in a dose-dependent manner and suppressed their capacities of clone formation, migration and invasion. Rev-treated cells exhibited reduced matrix metalloproteinase (MMP)2/9 expression and increased apoptosis compared with those in control cells. In addition, expression of the anti-apoptotic protein Bcl-2 was significantly decreased, whilst the expression levels of the pro-apoptotic factors Bax and cleaved-caspase-3/9 were increased by Rev treatment compared with that in the control group that were not treated with Rev. In addition, TTK protein expression was decreased in cells treated with Rev compared with that in untreated cells. However, overexpression of TTK significantly reversed the aforementioned effects of Rev in GC cells. These results suggest that Rev may inhibit the proliferation, invasion and migration of GC cells whilst inducing cell apoptosis by suppressing TTK expression. Therefore, Rev may confer potential properties as a therapeutic anti-cancer agent. Additionally, TTK may serve as a molecular target for the treatment of gastric cancer.

15.
Adv Nutr ; 12(2): 374-383, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33786594

RESUMO

Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intakes have been reported to be associated with mortality; however, conclusions have been inconsistent. This review synthesized the evidence on the associations of SSB and ASB intakes with mortality from all causes, cardiovascular disease (CVD), and cancer among all populations (including general, diseased, or occupational populations, etc.). PubMed, EMBASE, Web of Science, Cochrane Library, ProQuest, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched up to March 2020. Fifteen studies including 17 cohorts were included in meta-analyses. Each serving (12 fluid ounces or 355 mL) increase in daily SSB consumption was associated with higher risks of all-cause (HR: 1.08; 95% CI: 1.04, 1.12; 11 cohorts with 965,851 participants) and CVD (HR: 1.08; 95% CI: 1.04, 1.12; 13 cohorts with 898,005 participants) mortality. The associations of ASB intakes with all-cause and CVD mortality were J-shaped, and HRs (95% CI) across different doses (0, 1, 1.5, 2, and 2.5 servings/d) were 1.00, 1.01 (0.99, 1.03), 1.04 (1.02, 1.07), 1.08 (1.05, 1.11), and 1.13 (1.09, 1.18) for all-cause mortality and 1.00, 1.01 (0.96, 1.07), 1.07 (1.01, 1.13), 1.15 (1.08, 1.23), and 1.25 (1.14, 1.37) for CVD mortality. No significant association was found for cancer mortality. According to the NutriGrade scoring system, the quality of evidence on the associations of SSB intakes with all-cause and CVD mortality was high, and the quality of evidence on other associations was low to moderate. In summary, higher SSB and ASB intakes were associated with higher risks of all-cause mortality and CVD mortality. Given the limited evidence, future studies should further investigate the association between ASB intakes and cause-specific mortality.


Assuntos
Bebidas Adoçadas com Açúcar , Edulcorantes , Bebidas Adoçadas Artificialmente , Bebidas/efeitos adversos , Bebidas/análise , Humanos , Estudos Prospectivos , Edulcorantes/efeitos adversos
16.
J Neurosci Res ; 99(4): 1048-1063, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33404121

RESUMO

Glial cell line-derived neurotrophic factor (GDNF) is released by glioma cells and promotes tumor growth. We have previously found that GDNF released from the tumor cells is a chemoattractant for microglial cells, the immune cells of the central nervous system. Here we show that GDNF increases matrix metalloproteinase (MMP) 9 and MMP14 expression in cultured microglial cells from mixed sexes of neonatal mice. The GDNF-induced microglial MMP9 and MMP14 upregulation is mediated by GDNF family receptor alpha 1 receptors and dependent on p38 mitogen-activated protein kinase signaling. In organotypic brain slices, GDNF promotes the growth of glioma and this effect depends on the presence of microglia. We also previously found that MMP9 and MMP14 upregulation can be mediated by Toll-like receptor (TLR) 2 signaling and here we demonstrate that GDNF increases the expression of TLR1 and TLR2. In conclusion, GDNF promotes the pro-tumorigenic phenotype of microglia.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Glioma/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Animais , Linhagem Celular Tumoral , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Humanos , Imidazóis/farmacologia , Masculino , Metanálise como Assunto , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Cultura Primária de Células , Piridinas/farmacologia , Transdução de Sinais , Receptor 1 Toll-Like/metabolismo , Receptor 2 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Cell Mol Neurobiol ; 41(2): 365-375, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32410107

RESUMO

Glioma is the most common and fatal primary brain tumor in human. Long non-coding RNA (lncRNA), which are characterized by regulation of gene expression and chromatin recombination play an important role in glioma, and immunotherapy is a promising cancer treatment. Therefore, it is necessary to identify Immune-related lncRNAs in glioma. In this study,we collected and evaluated the RNA-seq data of The Cancer Genome Atlas (TCGA, https://www.ncbi.nlm.nih.gov/ ) and Chinese Glioma Genome Atlas (CGGA, https://www.cgga.org.cn/ ) glioma patients and immune-related lncRNAs were screened. Cox regression and LASSO analysis were performed to construct a risk score formula to explor the different overall survival between high- and low-risk groups in TCGA and verified with CGGA. Gene ontology (GO) and pathway-enrichment analysis (KEGG) were performed to identify the function of screened genes. Co-expression network were performed of these genes for further analysis. Eleven immune-related lncRNAs were concerned to be involved in survival and adopted to construct the risk score formula. Patients with high-risk score held poor survival both in TCGA and CGGA. Compared with current clinical data, the Area Under Curve (AUC) of different years and Principal components analysis (PCA) suggested that the formula had better predictive power. Functional Annotation of immune-related lncRNAs showed that the differences overall survival of high and low RS group might be caused by the cell differentiation, microtubule polymerization, etc. We successfully constructed an immune-related lncRNAs formula with powerful predictive function, which provides certain guidance value to the analysis of glioma pathogenesis and clinical treatment, and potential therapeutic targets for glioma treatment.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Perfilação da Expressão Gênica , Glioma/genética , Glioma/imunologia , RNA Longo não Codificante/genética , Algoritmos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Anotação de Sequência Molecular , Análise de Componente Principal , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/metabolismo , Reprodutibilidade dos Testes , Análise de Sobrevida
18.
Cell Signal ; 79: 109886, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33340660

RESUMO

Bladder cancer (BC) is one of the most common tumours of the urinary system and is also known as a highly malignant tumour. In addition to conventional diagnosis and treatment methods, recent research has focused on studying the molecular mechanisms related to BC, in the hope that new, less toxic and effective targeted anticancer drugs and new diagnostic markers can be discovered. It is known that the Wingless (Wnt) signalling pathway and its related genes, proteins and other substances are involved in multiple biological processes of various tumours. Clarifying the contribution of the Wnt signalling pathway in bladder tumours will help establish early diagnosis indicators, develop new therapeutic drugs and evaluate the prognosis for BC. This review aims to summarise previous studies related to BC and the Wnt signalling pathway, with a focus on exploring the participating substances and their mechanisms in the regulation of the Wnt signalling pathway to better determine how to promote new chemotherapeutic drugs, potential therapeutic targets and diagnostic biomarkers.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Via de Sinalização Wnt , Animais , Humanos , Proteínas de Neoplasias/genética , Neoplasias da Bexiga Urinária/genética
19.
Per Med ; 18(1): 9-19, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33052074

RESUMO

Aim: To investigate whether long non-coding RNAs (lncRNAs) can be utilized as molecular biomarkers in predicting the occurrence and progression of chromophobe renal cell carcinoma. Methods & results: Genetic and related clinical traits of chromophobe renal cell carcinoma were downloaded from the Cancer Genome Atlas and used to construct modules using weighted gene coexpression network analysis. In total, 44,889 genes were allocated into 21 coexpression modules depending on intergenic correlation. Among them, the green module was the most significant key module identified by module-trait correlation calculations (R2 = 0.43 and p = 4e-04). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that genes in the green module were enriched in many pathways. Coexpression, protein-protein interaction networks, screening for differentially expressed genes, and survival analysis were used to select hub lncRNAs. Five hub lncRNAs (TTK, CENPE, KIF2C, BUB1, and RAD51AP1) were selected out. Conclusion: Our findings suggest that the five lncRNAs may act as potential biomarkers for chromophobe renal cell carcinoma progression and prognosis.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , RNA Longo não Codificante/biossíntese , Biomarcadores Tumorais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Mapas de Interação de Proteínas , Análise de Sobrevida
20.
Neurosurg Rev ; 44(1): 479-484, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31953781

RESUMO

Atorvastatin therapy in chronic subdural hematoma patients has attracted more and more clinical attention. To evaluate the efficacy of atorvastatin in the treatment of chronic subdural hematoma. A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases; related controlled trials comparing the efficacy of atorvastatin in the treatment of chronic subdural hematoma published from inception to December 2018 were collected. We used Cochrane risk of bias method to evaluate the quality of the included studies. Meta-analysis was used to analyze the included data by RevMan 5.3 software. Of the 53 retrieved studies, 6 trials were included. Results of meta-analysis showed that compared with chronic subdural hematoma patients without atorvastatin treatment, both in patients who have had surgery and those who have not, atorvastatin were effective in reducing the incidence of recurrence requires surgery (OR = 0.30, 95% CI 0.19-0.48, P < 0.00001). And improve the recovery rate of neurological function of patients (OR = 1.75, 95% CI 1.08-2.83, P = 0.02). This meta-analysis suggests that patients with chronic subdural hematoma can improve their prognosis after receiving atorvastatin. Additionally, the neurological function recovery appears to be improving by atorvastatin.


Assuntos
Atorvastatina/uso terapêutico , Hematoma Subdural Crônico/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Humanos , Resultado do Tratamento
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