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1.
J Hazard Mater ; 476: 135067, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38964039

RESUMO

Endocrine-disrupting chemicals (EDCs) are persistent and pervasive compounds that pose serious risks. Numerous studies have explored the effects of EDCs on human health, among which tumors have been the primary focus. However, because of study design flaws, lack of effective exposure levels of EDCs, and inconsistent population data and findings, it is challenging to draw clear conclusions on the effect of these compounds on tumor-related outcomes. Our study is the first to systematically integrate observational studies and randomized controlled trials from over 20 years and summarize over 300 subgroup associations. We found that most EDCs promote tumor development, and that exposure to residential environmental pollutants may be a major source of pesticide exposure. Furthermore, we found that phytoestrogens exhibit antitumor effects. The findings of this study can aid in the development of global EDCs regulatory health policies and alleviate the severe risks associated with EDCs exposure.

2.
Chem Biodivers ; : e202401165, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973453

RESUMO

Bisindole compounds constitute a significant class of natural compounds distinguished by their characteristic bisindole structure and renowned for their anticancer properties. Over the past four decades, researchers have isolated 229 animal-derived bisindole compounds (ADBCs) from various animals. These compounds demonstrate a wide range of pharmacological properties, including cytotoxicity, antibacterial, antifungal, antiviral, and other activities. Notably, among these activities, cytotoxicity emerges as the most prominent characteristic of ADBCs. This review also summarizes the structureactivity relationship (SAR) studies associated with the cytotoxicity of these compounds and explores the druggability of these compounds. In summary, our objective is to provide an overview of the research progress concerning ADBCs, with the aim of fostering their continued development and utilization.

3.
Nat Prod Res ; : 1-7, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980258

RESUMO

Pactermines E and F (1 and 2), two new pregnane alkaloids were isolated from the whole plant of Pachysandra terminalis Sieb. et Zucc. Their structures were determined by physicochemical properties and spectroscopic methods including 1D, 2D NMR, IR, HR-ESI-MS data. Cytotoxic activities against three human cancer A549, HCT116 and SW620 cell lines of the isolated compounds were evaluated by CCK8 method. However, all compounds showed no significant activity against the three cancer cells (IC50>100 µM) except for compound 1, which showed inhibitory effects against HCT116 cells with IC50 values of 84.6 µM.

4.
Cell Metab ; 36(6): 1320-1334.e9, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38838643

RESUMO

Circadian homeostasis in mammals is a key intrinsic mechanism for responding to the external environment. However, the interplay between circadian rhythms and the tumor microenvironment (TME) and its influence on metastasis are still unclear. Here, in patients with colorectal cancer (CRC), disturbances of circadian rhythm and the accumulation of monocytes and granulocytes were closely related to metastasis. Moreover, dysregulation of circadian rhythm promoted lung metastasis of CRC by inducing the accumulation of myeloid-derived suppressor cells (MDSCs) and dysfunctional CD8+ T cells in the lungs of mice. Also, gut microbiota and its derived metabolite taurocholic acid (TCA) contributed to lung metastasis of CRC by triggering the accumulation of MDSCs in mice. Mechanistically, TCA promoted glycolysis of MDSCs epigenetically by enhancing mono-methylation of H3K4 of target genes and inhibited CHIP-mediated ubiquitination of PDL1. Our study links the biological clock with MDSCs in the TME through gut microbiota/metabolites in controlling the metastatic spread of CRC, uncovering a systemic mechanism for cancer metastasis.


Assuntos
Relógios Circadianos , Microbioma Gastrointestinal , Células Supressoras Mieloides , Animais , Camundongos , Células Supressoras Mieloides/metabolismo , Humanos , Metástase Neoplásica , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , Camundongos Endogâmicos C57BL , Masculino , Microambiente Tumoral , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/metabolismo , Feminino , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral
5.
J Hazard Mater ; 474: 134736, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38815394

RESUMO

We established an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously analyzing the metabolites of bisphenols and phthalates in urine to identify the associations between these exposure levels and prostate cancer (PCa) based on a case-control study. After purifying urine samples with SPE, 18 metabolites were separated on a C18 column, and MS detection was performed. The UPLC-MS/MS method has been proven effective at evaluating bisphenol and phthalate exposure (0.020-0.20 µg/L of the limits of detection, 71.8 %∼119.4 % of recoveries, 0.4 %∼8.2 % of precision). Logistic regression explored the association between exposure level and PCa in 187 PCa cases and 151 controls. The detection rates of bisphenol A (BPA) and most phthalate metabolites were 100 % ranging from 0.06-46.74 and 0.12-899.92 µg/g creatinine, respectively, while the detection rates of other bisphenols and mono-benzyl phthalate (MBzP) are low, ranging from 0 % to 21.85 %. Correlation analysis of the metabolite levels indicated that the exposure sources of BPA, di-ethyl phthalate (DEP), and di(2-ethylhexyl) phthalate (DEHP) were different, and that the exposure sources of di-n-butyl phthalate (DnBP) and di-isobutyl phthalate (DiBP) may differ between two groups. Logistic regression analysis revealed that BPA (OR<0.45 vs ≥1.43 =10.02) and DEHP exposure (OR<21.75 vs ≥45.42 =48.26) increased the risk of PCa.


Assuntos
Compostos Benzidrílicos , Exposição Ambiental , Fenóis , Ácidos Ftálicos , Neoplasias da Próstata , Neoplasias da Próstata/urina , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/epidemiologia , Masculino , Fenóis/urina , Fenóis/análise , Humanos , Ácidos Ftálicos/urina , Ácidos Ftálicos/análise , Compostos Benzidrílicos/urina , Estudos de Casos e Controles , Pessoa de Meia-Idade , Idoso , Exposição Ambiental/análise , Espectrometria de Massas em Tandem , Poluentes Ambientais/urina , Poluentes Ambientais/análise , Cromatografia Líquida de Alta Pressão
6.
BMJ Med ; 3(1): e000451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800667

RESUMO

Objective: To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death. Design: Prospective cohort study. Setting: UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years). Participants: 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study. Main outcome measures: Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). Results: Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99). Conclusions: Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

7.
Eur J Med Chem ; 271: 116445, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38701715

RESUMO

Lignans are widely distributed in nature, primarily found in the xylem and resins of plants, with the constituent units C6-C3, and their dimers are the most common in plants. In recent years, the trimeric sesquilignans have also received increasing attention from scholars. More than 200 derivatives have been isolated and identified from nearly 50 families, most of which are different types (monoepoxy lignans, bisepoxy lignans, benzofuran lignans) connected with simple phenylpropanoids through ether bonds, C-C bonds, and oxygen-containing rings to constitute sesquilignans. Some of them also possess pharmacological properties, including antioxidants, hepatoprotectives, antitumors, anti-inflammatory properties, and other properties. In addition, the chemical structure of sesquilignans is closely related to the pharmacological activity, and chemical modification of methoxylation enhances the pharmacological activity. In contrast, phenolic hydroxyl and hydroxyl glycosides reduce the pharmacological activity. Therefore, the present review aims to summarize the chemical diversity, bioactivities, and constitutive relationships to provide a theoretical basis for the more profound development and utilization of sesquilignans.


Assuntos
Lignanas , Lignanas/química , Lignanas/farmacologia , Lignanas/isolamento & purificação , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Estrutura Molecular , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia
8.
Int J Surg ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38759694

RESUMO

BACKGROUND: Testicular cancer (TC) is currently the most common malignancy in young and middle-aged men. A comprehensive assessment of TC burden is in lack. METHOD: Global incidence, deaths, and disability-adjusted life-years (DALYs) of TC from 1990 to 2019 were obtained. Estimated annual percentage change (EAPC) was calculated to quantify trends in TC changes during the period. Relationships between disease burden and age, sociodemographic index (SDI) levels, human development index (HDI) were further analyzed. RESULTS: Globally, incident cases of TC more than doubled from 1990 to 2019, together with an increasing of global age-standardized incidence rates (ASIR) of TC from 1.9 to 2.8. The age-standardized deaths rates (ASDR) remained stable from 0.31 to 0.28. The similar results were reflected in the disability-adjusted life-years (DALYs). In 2019, the highest ASIR were found in Southern Latin America, Central Europe and Western Europe. Analogously, the highest ASDR were found in Southern Latin America followed by Central Latin America and Central Europe. The burden of incidence increased with SDI, appropriately reached a peak at about 0.78, and then declined. Similarly, the burden of deaths increased with SDI, met a maximum at about 0.7. CONCLUSIONS: From 1990 to 2019, the ASIR of TC has increased significantly, while the ASDR has been relatively stable and slightly decreased. The disease burden of TC is shifting to regions and countries with moderate to high levels of development. TC remains a rapidly growing global health problem, and new changes in TC burden should be considered when formulating new TC control policies.

9.
BMC Cancer ; 24(1): 291, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438842

RESUMO

BACKGROUND: For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral therapy for hepatocellular carcinoma (HCC) remains to be further explored. METHODS: 196 HBV-related HCC patients who received radical hepatectomy and nucleos(t)ide analogues (NAs) therapy at Sichuan Provincial People's Hospital were enrolled in this study. HCC recurrence, overall survival (OS), early virological (VR) and biochemical responses (BR) of patients were compared between different NAs therapy and the use of anti-programmed cell death protein 1 (PD-1) therapy. RESULTS: NAs therapy at different timing of surgery was a strong independent risk factor for postoperative recurrence and overall mortality of HBV-related HCC patients. Furthermore, in HCC patients who received postoperative anti-PD-1 therapy, patients with HBV DNA < 1000 copy/mL had significantly better recurrence-free survival (RFS) and OS than those with HBV DNA ≥ 1000 copy/mL (HR: 7.783; P = 0.002; HR: 6.699; P < 0.001). However, the differences of RFS and OS rates between entecavir group and tenofovir disoproxil fumarate group were not statistically significant. Similar results were also observed in the rates of early VR, BR and combined VR and BR. CONCLUSION: Timely and reasonable preoperative NAs therapy showed clinical benefit in improving the prognosis of patients with HBV-related HCC, even in the case of normal alanine aminotransferase (ALT) level and negative hepatitis e antigen (HBeAg). Furthermore, a possible synergistic effect between antiviral therapy and anti-PD-1 therapy was founded and need further verification.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Vírus da Hepatite B , DNA Viral , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Prognóstico , Antivirais/uso terapêutico
11.
Micromachines (Basel) ; 15(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38398900

RESUMO

In the laser powder bed fusion additive manufacturing process, the quality of fabrications is intricately tied to the laser-matter interaction, specifically the formation of the melt pool. This study experimentally examined the intricacies of melt pool characteristics and surface topography across diverse laser powers and speeds via single-track laser scanning on a bare plate and powder bed for 316L stainless steel. The results reveal that the presence of a powder layer amplifies melt pool instability and worsens irregularities due to increased laser absorption and the introduction of uneven mass from the powder. To provide a comprehensive understanding of melt pool dynamics, a high-fidelity computational model encompassing fluid dynamics, heat transfer, vaporization, and solidification was developed. It was validated against the measured melt pool dimensions and morphology, effectively predicting conduction and keyholing modes with irregular surface features. Particularly, the model explained the forming mechanisms of a defective morphology, termed swell-undercut, at high power and speed conditions, detailing the roles of recoil pressure and liquid refilling. As an application, multiple-track simulations replicate the surface features on cubic samples under two distinct process conditions, showcasing the potential of the laser-matter interaction model for process optimization.

12.
Comput Biol Med ; 169: 107943, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38211382

RESUMO

BACKGROUND: Breast cancer is the most prevalent malignancy in women. Advanced breast cancer can develop distant metastases, posing a severe threat to the life of patients. Because the clinical warning signs of distant metastasis are manifested in the late stage of the disease, there is a need for better methods of predicting metastasis. METHODS: First, we screened breast cancer distant metastasis target genes by performing difference analysis and weighted gene co-expression network analysis (WGCNA) on the selected datasets, and performed analyses such as GO enrichment analysis on these target genes. Secondly, we screened breast cancer distant metastasis target genes by LASSO regression analysis and performed correlation analysis and other analyses on these biomarkers. Finally, we constructed several breast cancer distant metastasis prediction models based on Logistic Regression (LR) model, Random Forest (RF) model, Support Vector Machine (SVM) model, Gradient Boosting Decision Tree (GBDT) model and eXtreme Gradient Boosting (XGBoost) model, and selected the optimal model from them. RESULTS: Several 21-gene breast cancer distant metastasis prediction models were constructed, with the best performance of the model constructed based on the random forest model. This model accurately predicted the emergence of distant metastases from breast cancer, with an accuracy of 93.6 %, an F1-score of 88.9 % and an AUC value of 91.3 % on the validation set. CONCLUSION: Our findings have the potential to be translated into a point-of-care prognostic analysis to reduce breast cancer mortality.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Mama , Perfilação da Expressão Gênica , Modelos Logísticos , Aprendizado de Máquina
13.
Prostate ; 84(6): 539-548, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38173301

RESUMO

BACKGROUND: Data on the utilization and effects of prebiopsy prostate multiparametric magnetic resonance imaging (mpMRI) to support its routine use in real-world setting are still scarce. OBJECTIVE: To evaluate the change of clinical practice of prebiopsy mpMRI over time, and assess its diagnostic accuracy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 6168 patients who underwent primary prostate biopsy (PBx) between January 2011 and December 2021 and had prostate-specific antigen (PSA) values ranging from 3 to 100 ng/mL. INTERVENTION: Prebiopsy MRI at the time of PBx. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed general linear regression and to elucidate trends in the annual use of prebiopsy mpMRI and conducted multivariable logistic regression to evaluate the potential benefits of incorporating prebiopsy mpMRI for prostate cancer (PCa) detection. RESULTS AND LIMITATIONS: The utilization of prebiopsy mpMRI significantly increased from 9.2% in 2011 to 75.0% in 2021 (p < 0.001). In addition, prebiopsy mpMRI significantly reduced negative PBx by 8.6% while improving the detection of clinically significant PCa (csPCa) by 7.0%. Regression analysis showed that the utilization of prebiopsy mpMRI was significantly associated with a 48% (95% confidence interval [CI]: 1.19-1.84) and 36% (95% CI: 1.12-1.66) increased PCa detection rate in the PSA 3-10 ng/mL and 10-20 ng/mL groups, respectively; and a 34% increased csPCa detection rate in the PSA 10-20 ng/mL group (95% CI: 1.09-1.64). The retrospective design and the single center cohort constituted the limitations of this study. CONCLUSIONS: Our study demonstrated a notable rise in the utilization of prebiopsy mpMRI in the past decade. The adoption of this imaging technique was significantly associated with an increased probability of detecting prostate cancer. PATIENT SUMMARY: From 2011 to 2021, we demonstrated a steady increase in the utilization of prebiopsy mpMRI among biopsy-naïve men. We also confirmed the positive impact of prebiopsy mpMRI utilization on the detection of prostate cancer.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Antígeno Prostático Específico , Próstata/diagnóstico por imagem , Próstata/patologia , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Biópsia Guiada por Imagem/métodos
14.
Cell Metab ; 36(3): 541-556.e9, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38232736

RESUMO

The roles of platelets/megakaryocytes (MKs), the key components in the blood system, in the tumor microenvironment and antitumor immunity are unclear. In patients with colorectal cancer, the number of platelets was significantly increased in patients with metastasis, and Erbin expression was highly expressed in platelets from patients with metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasis in mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient platelets have increasing mitochondrial oxidative phosphorylation and secrete lipid metabolites like acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM. Notably, Acar enhanced the activity of mitochondrial electron transport chain complex and mitochondrial oxidative phosphorylation in B cells by acetylation of H3K27 epigenetically. Targeting Erbin in platelets/MKs by a nanovesicle system dramatically attenuated lung metastasis in mice in vivo. Our study identifies an Erbin-mitochondria axis in platelets/MKs, which suppresses B cell-mediated antitumor immunity, suggesting a new way for the treatment of metastasis.


Assuntos
Neoplasias Pulmonares , Megacariócitos , Animais , Humanos , Camundongos , Plaquetas/metabolismo , Neoplasias Pulmonares/metabolismo , Megacariócitos/metabolismo , Mitocôndrias/metabolismo , Processamento de Proteína Pós-Traducional , Microambiente Tumoral
15.
EClinicalMedicine ; 64: 102230, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37936651

RESUMO

Background: Cardiovascular disease (CVD) remains a paramount contemporary health challenge. This study examined age-specific effects of 14 risk factors on CVD and mortality in different age groups. Methods: We analyzed data from 226,759 CVD-free participants aged 40 years and older in the UK Biobank during the period from baseline time (2006-2010) to September 30, 2021. The primary CVD outcome was a composite of incident coronary artery disease, heart failure, and stroke. We calculated age-specific hazard ratios (HRs) and population-attributable fractions (PAF) for CVD and mortality associated with 14 potentially modifiable risk factors. Findings: During 12.17-year follow-up, 23,838 incident CVD cases and 11,949 deaths occurred. Age-specific disparities were observed in the risk factors contributing to CVD, and the overall PAF declined with age (PAF of 56.53% in middle-age; 49.78% in quinquagenarian; 42.45% in the elderly). Metabolic factors had the highest PAF in each age group, with hypertension (14.04% of the PAF) and abdominal obesity (9.58% of the PAF) being prominent. Behavioral factors had the highest PAF in the middle-aged group (10.68% of the PAF), and smoking was the leading behavioral factor in all age groups. In socioeconomic and psychosocial risk clusters, low income contributed most among middle-aged (3.74% of the PAF) and elderly groups (3.66% of the PAF), while less education accounted more PAF for quinquagenarian group (4.46% of the PAF). Similar age-specific patterns were observed for cardiovascular subtypes and mortality. Interpretation: A large fraction of CVD cases and deaths were associated with modifiable risk factors in all age groups. Targeted efforts should focus on the most impactful risk factors, as well as age-specific modifiable risk factors. These findings may inform the development of more precise medical strategies to prevent and manage CVD and related mortality. Funding: The work was supported by the Bill & Melinda Gates Foundation (grant number: INV-016826 to Hualiang Lin) and the National Natural Science Foundation of China (grant number: 82373534 to Hualiang Lin).

16.
Arq Bras Cardiol ; 120(11): e20230395, 2023 10.
Artigo em Inglês, Português | MEDLINE | ID: mdl-37909538

RESUMO

BACKGROUND: Many clinical studies have confirmed that legumain is closely related to atherosclerosis. Unfortunately, different conclusions have been reached, and analyses and studies on atherosclerotic plaque characteristics in patients with increased plasma levels of legumain are still lacking. OBJECTIVES: This study aimed to investigate the correlation between legumain and coronary atherosclerotic plaque characteristics. METHODS: A total of 81 patients with coronary atherosclerotic heart disease (CHD), including 43 patients with unstable angina (UA) and 38 patients with stable angina (SA), were screened by coronary angiography. Intravascular ultrasound (IVUS) was performed to evaluate the characteristics of coronary atherosclerotic plaques, and plasma legumain levels were also measured. Values of p < 0.05 were considered significant. RESULTS: Legumain concentration was significantly higher in the two CHD subgroups than in the control group (all p<0.001). Legumain concentrations in the UA group were significantly higher than in the SA group (p=0.001). The plaque area, remodeling index (RI), and eccentricity index (EI) in the UA group were significantly higher than those in the SA group (p<0.001, p=0.001, p=0.001, respectively). There was a significant positive correlation between legumain levels and RI and EI in both UA and SA patients (all p<0.05). CONCLUSIONS: High plasma levels of legumain were closely related to the occurrence and severity of CHD, and the lesions tended to be unstable. Legumain is expected to be a potential inflammatory biomarker for the diagnosis of CHD and the early identification of unstable coronary lesions.


FUNDAMENTO: Muitos estudos clínicos confirmaram que a legumain está intimamente relacionada à aterosclerose. Infelizmente, chegaram-se a conclusões diferentes e ainda faltam análises e estudos sobre as características da placa aterosclerótica em pacientes com níveis plasmáticos aumentados de legumain. OBJETIVOS: Este estudo teve como objetivo investigar a correlação entre as características da legumain e da placa aterosclerótica coronariana. MÉTODOS: Um total de 81 pacientes com doença cardíaca aterosclerótica coronariana (DCAC), incluindo 43 pacientes com angina instável (AI) e 38 pacientes com angina estável (AE), foram examinados por angiografia coronária. Foi realizado ultrassom intravascular (IVUS) para avaliar as características das placas ateroscleróticas coronarianas, e os níveis plasmáticos de legumain também foram medidos. Valores de p < 0,05 foram considerados significativos. RESULTADOS: A concentração de legumain foi significativamente maior nos dois subgrupos de doença coronariana do que no grupo controle (todos p<0,001). As concentrações de legumain no grupo AI foram significativamente maiores do que no grupo SA (p=0,001). A área de placa, o índice de remodelamento (IR) e o índice de excentricidade (IE) no grupo AI foram significativamente maiores do que no grupo AE (p<0,001, p=0,001, p=0,001, respectivamente). Houve uma correlação positiva significativa entre os níveis de legumain e IR e IE em pacientes com AI e AE (todos p<0,05). CONCLUSÕES: Níveis plasmáticos elevados de legumain estavam intimamente relacionados com a ocorrência e gravidade da doença coronariana, e as lesões tendiam a ser instáveis. Espera-se que a legumain seja um potencial biomarcador inflamatório para o diagnóstico de doença coronariana e a identificação precoce de lesões coronárias instáveis.


Assuntos
Angina Estável , Aterosclerose , Doença da Artéria Coronariana , Doença das Coronárias , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Angina Instável/diagnóstico por imagem , Cisteína Endopeptidases , Angiografia Coronária , Ultrassonografia de Intervenção
17.
Curr Drug Targets ; 24(14): 1079-1092, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37846578

RESUMO

The BET protein family plays a crucial role in regulating the epigenetic landscape of the genome. Their role in regulating tumor-related gene expression and its impact on the survival of tumor cells is widely acknowledged. Among the BET family constituents, BRD4 is a significant protein. It is a bromodomain-containing protein located at the outer terminal that recognizes histones that have undergone acetylation. It is present in the promoter or enhancer region of the target gene and is responsible for initiating and sustaining the expression of genes associated with tumorigenesis. BRD4 expression is significantly elevated in various tumor types. Research has indicated that BRD4 plays a significant role in regulating various transcription factors and chromatin modification, as well as in repairing DNA damage and preserving telomere function, ultimately contributing to the survival of cancerous cells. The protein BRD4 has a significant impact on antitumor therapy, particularly in the management of lung cancer and hematological malignancies, and the promising potential of BRD4 inhibitors in the realm of cancer prevention and treatment is a topic of great interest. Therefore, BRD4 is considered a promising candidate for prophylaxis and therapy of neoplastic diseases. However, further research is required to fully comprehend the significance and indispensability of BRD4 in cancer and its potential as a therapeutic target.


Assuntos
Neoplasias Hematológicas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Nucleares/genética , Fatores de Transcrição/metabolismo , Proteínas de Ciclo Celular , Neoplasias Hematológicas/tratamento farmacológico , Proteínas que Contêm Bromodomínio
18.
Inflamm Bowel Dis ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37889850

RESUMO

BACKGROUND: We examined the associations of fish and fish oil consumption with inflammatory bowel disease (IBD) incidence. PATIENTS AND METHODS: We conducted a longitudinal analysis based on the UK Biobank, a population-based prospective cohort. Dietary consumption of fish and fish oil was collected by questionnaire. IBD incident cases were identified through links to National Health Services datasets. Cox proportional hazards regression models were used to assess the associations between oily fish, nonoily fish, and fish oil intake and IBD incidence with adjustment for various confounding factors. RESULTS: A total of 265 839 participants free of IBD at baseline were included, and 1554 incident IBD cases were identified during an average follow-up of 11.8 years. In fully adjusted models, we found that compared with participants who never ate oily fish, those having <1 serving/wk, 1 serving/wk, and >1 serving/wk had 9% (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.77-1.08), 19% (HR, 0.81; 95% CI, 0.69-0.96), and 12% (HR, 0.88; 95% CI, 0.73-1.06) lower risks of IBD, respectively, albeit not all statistically significant. A significant association was found between fish oil intake and a reduced risk of IBD (HR, 0.84; 95% CI, 0.75-0.93). We found no significant associations for nonoily fish. In a subsample (n = 105 714) of participants with multiple subsequent dietary reviews, we also found a negative association between the frequency of fish oil intake over time and incident IBD (P trend < .05). CONCLUSIONS: Our findings indicate that oily fish and fish oil supplements might be protective factors against IBD.


Individuals who regularly consumed oily fish had a reduced risk of inflammatory bowel disease (IBD). Fish oil supplementation was also linked with a reduced risk of IBD. By contrast, no significant association was observed between nonoily fish intake and IBD.

19.
Phys Chem Chem Phys ; 25(34): 22565-22582, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37608735

RESUMO

In the last decade, oil-based titanium dioxide nanofluids (TiO2 NFs) have gained immense interest due to their unique insulating properties and excellent thermal performance, which endow them with the potential for application in the field of modified insulating oils. A timely comparison, analysis and summary of recent advances in the preparation, characterization, and properties of different oil-based TiO2 NFs for oil-immersed power transformers will contribute to provide a useful reference for the subsequent development of such materials. Preparation methods are reviewed along with their merits and demerits. Characterization techniques including scanning electron microscopy (SEM), transmission electron microscopy (TEM), optical microscopy (OM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, thermally stimulated current (TSC), pulse electroacoustic technique (PEA), finite element analysis (FEA), fluorescence spectroscopy, Raman spectroscopy and zeta potential analysis are all applied to determine the crystal structure, particle size, surface function, surface charge and stability. Stabilization mechanisms are also discussed in detail. Some critical properties of oil-based TiO2 NFs under the application of different influencing factors such as base oils, crystal structure, size of nanoparticles, surface modifiers, mixing percentage, and aging environment are highlighted. Finally, the existing challenges and perspectives are presented for future research.

20.
BMC Public Health ; 23(1): 1632, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37626316

RESUMO

BACKGROUND: Increasing body fat or decreasing muscle and bone mass were associated with worse health outcomes in the adult population. The effects of nickel exposure on body composition are not known. The aim of the current study was to investigate the relationship between urinary nickel levels and body compositions. MATERIALS AND METHODS: Two thousand seven hundred sixty-two participants were included in the analysis from the National Health and Nutrition Examination Surveys of 2017-2018 after excluding participants who have missing data on urinary nickel and those with missing all body mass component data. We used weighted generalized linear models to explore the relationship between urinary nickel and body mass components under interpolating missing covariable values. Simultaneously, sensitivity analyses and subgroup analysis were conducted to verify stability of analysis result. Curve fitting and saturation effect analysis were used to explore the possible nonlinear relationship between urine nickel and body compositions. RESULTS: Among the 2,762 participants, the average urinary nickel level was 1.58 ug/L. The weighted generalized linear models, the sensitivity analyses and subgroup analyses found no significant linear relationship between urinary nickel and body compositions. For body weight, BMI, TLM, ALM, TRF, TOF and BMC, the urine nickel saturation effect values were 0.76, 0.74, 0.5, 0.67, 0.64, 0.48, and 0.45 ug/L, respectively. For each 1 ug/L rise in urinary nickel levels at levels below the turning point, body weight increases (ß = 9.06, 95% CI = 2.75, 15.36, p = 0.01), BMI increases (ß = 3.20, 95% CI = 1.36, 5.05, p = < 0.001), TLM decreases (ß = -47.39, 95% CI = -97.38, 2.59, p = 0.06), ALM decreases (ß = -37.25, 95% CI = -63.25, -11.24, p = 0.01), TRF increases (ß = 20.68, 95% CI = 1.50, 39.86, p = 0.03), TOF increases (ß = 57.92, 95% CI = -0.12, 115.95, p = 0.05), and BMC decreases (ß = -6.84, 95% CI = -12.64, -1.04, p = 0.02). CONCLUSIONS: In summary, our study demonstrated that a dose-response relationship exists between urinary nickel and body compositions, with a low inflection point level of urinary nickel for the saturation effect.


Assuntos
Composição Corporal , Níquel , Adulto , Estados Unidos/epidemiologia , Humanos , Estudos Transversais , Tecido Adiposo , Aumento de Peso
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