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1.
RSC Adv ; 14(12): 8240-8250, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38482069

RESUMO

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

2.
Aging (Albany NY) ; 16(4): 4014-4032, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38393698

RESUMO

BACKGROUND: Breast cancer (BC) is a heterogeneous tumor with a variety of etiology and clinical features. Antibody-dependent cell phagocytosis (ADCP) is the last step of immune checkpoint inhibition (ICI), and macrophages detect and recognize tumor cells, then destroy and engulf tumor cells. Despite the large number, negative regulators that inhibit phagocytic activity are still a key obstacle to the full efficacy of ICI. PATIENTS AND METHODS: An ADCP-related risk score prognostic model for risk stratification as well as prognosis prediction was established in the Cancer Genome Atlas (TCGA) cohort. The predictive value of ADCP risk score in prognosis and immunotherapy was also further validated in the TCGA along with International Cancer Genome Consortium cohorts. To promote the clinical application of the risk score, a nomogram was established, with its effectiveness verified by different methods. RESULTS: In this study, the genes collected from previous studies were defined as ADCP-related genes. In BC patients, two ADCP-related subtypes were identified. The immune characteristics and prognostic stratification were significant different between them. CONCLUSIONS: We identified two subtypes associated with ADCP gene expression in breast cancer. They have significant differences in immune cells, molecular functions, HLA family genes, immune scores, stromal scores, and inflammatory gene expression, which have important guiding significance for the selection of clinical treatment methods. At the same time, we constructed a risk model based on ADCP, and the risk score can be used as a good indicator of prognosis, providing potential therapeutic advantages for chemotherapy and immunotherapy, thus helping the clinical decision-making of BC patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Citofagocitose , Prognóstico , Anticorpos , Nomogramas , Microambiente Tumoral
3.
Transl Cancer Res ; 13(1): 137-149, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38410222

RESUMO

Background: The anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunotherapy has been extensively used in patients with non-small cell lung cancer (NSCLC) in which the tumors are negative for oncogenic alterations. However, whether PD-1/PD-L1 blockade therapy could be applicable in patients harboring oncogenic mutations is largely unknown. Methods: In this retrospective study, we analyzed the safety and efficacy of anti-PD-1 inhibitor-based combinational therapy in a NSCLC cohort of 84 patients who harbored oncogenic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), k-Ras, RET, HER2 and BRAF. The patients were followed up till disease progression or death. The adverse effects associated with the treatment were carefully evaluated and timely interrupted. Results: There were 50 patients harboring EGFR mutations, 17 patients with k-Ras mutation, 2 patients with ALK rearrangement, 6 patients with RET rearrangement, 6 patients with HER2 exon20 insertion and 3 patients with BRAF V600E mutation. About 58.8% of the k-Ras mutant patients responded to the combinational treatment. The median progression-free survival (mPFS) of the k-Ras cohort was 14 months, with the 12-month median overall survival (mOS) ratio and the 24-month OS ratio of 86.7% and 75.8%, respectively. Patients with EGFR exon21 L858R mutation or RET rearrangement tended to have a more favorable response, while patients harboring ALK rearrangement, HER2 exon20 insertion and BRAF V600E mutation did not respond well to anti-PD-1 inhibitor-based combinational therapy. The incidence of treatment-related toxicity was 52.3% and the most common immune-related adverse events (irAEs) were PD-1 inhibitors-related hypothyroidism and pneumonitis. The PD-L1 status and lung immune prognostic index (LIPI) could be used as biomarkers dictating therapeutic outcomes of the combinational therapy. Conclusions: The anti-PD-1 inhibitor-based combinational therapy elicited exciting anti-tumor efficacy and prolonged patient survival with manageable adverse effects in NSCLC patients harboring oncogenic alterations. The PD-L1 status and LIPI could be used as a biomarker predicting response to anti-PD-1 inhibitor-based combinational treatment in these patients.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38279718

RESUMO

Leptomeningeal metastasis (LM) is a serious and often fatal complication in patients with advanced lung cancer, resulting in significant neurological deficits, decreased quality of life, and a poor prognosis. This article summarizes current research advances in treating lung cancer with meningeal metastases, discusses clinical challenges, and explores treatment strategies. Through an extensive review of relevant clinical trial reports and screening of recent conference abstracts, we collected clinical data on treating patients with lung cancer with meningeal metastases to provide an overview of the current research progress. Exciting progress has been made by focusing on specific mutations within lung cancer, including the use of EGFR tyrosine kinase inhibitors or inhibitors for anaplastic lymphoma kinase gene rearrangement, such as osimertinib, alectinib, and lorlatinib. These targeted therapies have shown impressive results in penetrating the central nervous system (CNS). Regarding whole-brain radiotherapy, there is currently some controversy among investigators regarding its effect on survival. Additionally, immune checkpoint inhibitors (ICIs) have demonstrated reliable clinical benefits due to their ability to retain anticancer activity in CNS metastases. Moreover, combination therapy shows promise in providing further treatment possibilities. Considerable progress has been made in the clinical research of lung cancer with LM. However, the sample size of prospective clinical trials investigating LM for lung cancer is still limited, with most reports being retrospective. Developing more effective management protocols for metastatic LM in lung cancer remains an ongoing challenge for the future.

7.
Liver Int ; 42(5): 1144-1157, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35274813

RESUMO

Cholangiocarcinoma (CCA) is a severe malignancy originating from the bile duct and the second most common primary liver cancer. NF-kappa B interacting lncRNA (NKILA) is a functional lncRNA, which play important role in human cancers. However, the role and underlying mechanism of NKILA in CCA remains largely unknown. Here, our study demonstrated that NKILA was significantly upregulated in CCA tissues and cells. Overexpression of NKILA is associated with advanced TNM stage, lymph node and distant metastasis, and also indicated poor prognosis in CCA patients. Functionally, NKILA facilitated CCA growth and metastasis in vitro and in vivo. The 5-methylcytosine (m5 C) methyltransferase NSUN2 interacts with NKILA, increasing its m5 C level and promoting its interaction with YBX1. Moreover, NKILA physically interacted with and suppressed miR-582-3p, which was regulated by METTL3-mediated N6 -methyladenosine (m6 A) modification. Finally, we showed that YAP1 was a target of NKILA via miR-582-3p and NKILA functioned partially via YAP1 in CCA. Taken together, our findings indicate a novel regulatory mechanism of NKILA for promoting CCA progression and that NKILA may be a promising target for CCA treatment.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , RNA Longo não Codificante/genética , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Metiltransferases/genética , MicroRNAs/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas de Sinalização YAP
8.
Front Pharmacol ; 13: 710099, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185555

RESUMO

Background: Linezolid-induced thrombocytopenia (LIT) is the main factor limiting the clinical application of linezolid (LZD). The incidence and risk factors of LIT in neonatal patients were possibly different from other populations based on pathophysiological characteristics. The purpose of this study was to establish a regression model for predicting LIT in neonatal sepsis patients. Methods: We retrospectively included 518 patients and divided them into the LIT group and the non-LIT group. A logistic regression analysis was used to analyze the factors related to LIT, and a regression model was established. A receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value. We prospectively collected 39 patients' data to validate the model and evaluate the effect of LZD pharmacokinetics on LIT. Results: Among the 518 patients, 103 patients (19.9%) developed LIT. The Kaplan-Meier plot revealed that the overall median time from the initiation of LZD treatment to the onset of LIT in preterm infants was much shorter when compared with term infants [10 (6, 12) vs. 13 (9.75, 16.5), p = 0.004]. Multiple logistic regression analysis indicated that the independent risk factors of LIT were lower weight at medication, younger gestational ages, late-onset sepsis, necrotizing enterocolitis, mechanical ventilation, longer durations of LZD treatment, and lower baseline of platelet level. We established the above seven-variable prediction regression model and calculated the predictive probability. The ROC curve showed that the predicted probability of combined body weight, gestational age, duration of LZD treatment, and baseline of platelet had better sensitivity (84.4%), specificity (74.2%), and maximum AUC (AUC = 0.873). LIT occurred in 9 out of 39 patients (23.1%), and the accuracies of positive and negative predictions of LIT were 88.9 and 76.7%, respectively. Compared with the non-LIT patients, the LIT patients had higher trough concentration [11.49 (6.86, 15.13) vs. 5.51 (2.80, 11.61) mg/L; p = 0.028] but lower apparent volume of distribution (Vd) [0.778 (0.687, 1.421) vs. 1.322 (1.099, 1.610) L; p = 0.010]. Conclusion: The incidence of LIT was high in neonatal sepsis patients, especially in preterm infants. LIT occurred earlier in preterm infants than in term infants. The regression model of seven variables had a high predictive value for predicting LIT. LIT was correlated with higher trough concentration and lower Vd.

9.
Nutrients ; 13(8)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34444874

RESUMO

This study was designed to examine the association of soy isoflavones (SI) intake with different body measurements indicative of obesity in Chinese adults of Shanghai, a population consuming foods rich in SI. This study used baseline data from the Shanghai Gaofeng cohort study. SI intake was measured by using a self-reported food frequency questionnaire (FFQ). A restricted cubic spline (RCS) was performed to examine the possible nonlinear relationship of SI intake with obesity. A logistic regression model was applied to estimate the odds ratios (OR) and 95% confidence interval (CI). Compared with the lowest tertile group of SI intake, the highest tertile group had a lower prevalence of obesity and central obesity. The OR for overall obesity was 0.91 (95% CI: 0.85, 0.98) in the highest versus the lowest SI tertile group; the associations differed by sex and menopausal status. A negative association was also observed between SI intake and central obesity, and a significant modifying effect of sex was found on the association. No significant interactions were observed between SI intake and physical activity (PA) levels. Our results suggest that Chinese adults with higher dietary intake of SI may be less likely to be obese, particularly for postmenopausal women.


Assuntos
Dieta , Isoflavonas/administração & dosagem , Obesidade/epidemiologia , Alimentos de Soja , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/prevenção & controle , Pós-Menopausa , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores Sexuais , Adulto Jovem
10.
Bioconjug Chem ; 32(8): 1554-1558, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34156824

RESUMO

Pretargeted positron emission tomography is a macromolecule-driven nuclear medicine technique that involves targeting a preadministered antigen target-bound macromolecule with a radioligand in vivo, aiming to minimize the overall radiation dose. This study investigates the use of antibody based host-guest chemistry methodology for pretargeted positron emission tomography. We hypothesize that the novel pretargeting approach reported here overcomes the challenges the current pretargeting platforms have with the in vivo stability and modularity of the pretargeting components. A cucurbit[7]uril host molecule modified, anti-carcinoembryonic antigen antibody (M5A; CB7-M5A) and a 68Ga-radiolabeled ferrocene guest radioligand ([68Ga]Ga-NOTA-PEG3-NMe2-Fc) were studied as potential host-guest chemistry pretargeting agents for positron emission tomography in BxPC3 xenografted nude mice. The viability of the platform was studied via in vivo biodistribution and positron emission tomography. Tumor uptake of [68Ga]Ga-NOTA-PEG3-NMe2-Fc was significantly higher in mice which received CB7-M5A prior to the radioligand injection (pretargeted) (3.3 ± 0.7%ID/g) compared to mice which only received the radioligand (nonpretargeted) (0.2 ± 0.1%ID/g).


Assuntos
Compostos Ferrosos/química , Compostos Macrocíclicos/química , Metalocenos/química , Neoplasias da Próstata/diagnóstico por imagem , Animais , Antígeno Carcinoembrionário/análise , Humanos , Imunoconjugados/química , Masculino , Camundongos Nus , Células PC-3 , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química
11.
Nutr Metab Cardiovasc Dis ; 31(7): 2058-2067, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34090771

RESUMO

BACKGROUND AND AIMS: The accuracy of various 10-year atherosclerotic cardiovascular disease (ASCVD) risk models has been debatable. We compared two risk algorithms and explored clustering patterns across different risk stratifications among community residents in Shanghai. METHODS AND RESULTS: A total of 28,201 residents (aged 40-74 years old) who were free of ASCVD were selected from the Shanghai Survey in China. The 10-year ASCVD risk was estimated by applying the 2013 Pooled Cohort Equations (PCEs) and Prediction for ASCVD Risk in China (China-PAR). The agreement was assessed between PCEs and China-PAR using Cohen's kappa statistics. The mean absolute 10-year ASCVD risk calculated by PCEs and China-PAR was about 10.0% and 6.0%, respectively. PCEs estimated that 44.9% of participants [with a 95% confidence interval (CI):44.0%-45.8%] were at high risk, while China-PAR estimated only 16.7% (95%CI:15.8%-18.0%) were at high risk. In both models, the percentage of high ASCVD risk was higher for participants who were older, men, less educated, current smokers, drinkers and manual workers. Among high-risk individuals, almost all participants (PCEs:90.5%; China-PAR:98.6%) had at least one risk factor; hypertension being the most prevalent. The concordance between PCEs and China-PAR was moderate (kappa:0.428, 95%CI: 0.420-0.434) with a better agreement for women (kappa:0.503,95%CI: 0.493-0.513) than for men (kappa:0.211,95%CI: 0.201-0.221). CONCLUSION: The proportion of participants with a 10-year ASCVD high risk predicted by China-PAR was lower than the results of the PCEs. The risk stratifications of the two algorithms were inconsistent in terms of demographic and life-behaviour characteristics.


Assuntos
Algoritmos , Aterosclerose/epidemiologia , Técnicas de Apoio para a Decisão , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Aterosclerose/diagnóstico , China/epidemiologia , Estudos Transversais , Escolaridade , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/epidemiologia , Descrição de Cargo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologia , Fatores de Tempo
12.
Cancer Manag Res ; 13: 3867-3878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34012295

RESUMO

OBJECTIVE: To identify people with high-risk early colorectal neoplasm is highly desirable for pre-selection in colorectal cancer (CRC) screening in low-resource countries. We aim to build and validate a risk-based model so as to improve compliance and increase the benefits of screening. PATIENTS AND METHODS: Using data from the Shanghai CRC screening cohort, we conducted a population-based nested case-control study to build a risk-based model. Cases of early colorectal neoplasm were extracted as colorectal adenomas and stage 0-I CRC. Each case was matched with five individuals without neoplasm (controls) by the screening site and year of enrollment. Cases and controls were then randomly divided into two groups, with two thirds for building the risk prediction model and the other one third for model validation. Known risk factors were included for risk prediction models using logistic regressions. The area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow chi-square statistics were used to evaluate model discrimination and calibration. The predicted individual risk probability was calculated under the risk regression equation. RESULTS: The model incorporating age, sex, family history and lifestyle factors including body mass index (BMI), smoking status, alcohol, regular moderate-to-intensity physical activity showed good calibration and discrimination. When the risk cutoff threshold was defined as 17%, the sensitivity and specificity of the model were 63.99% and 53.82%, respectively. The validation data analysis also showed well discrimination. CONCLUSION: A risk prediction model combining personal and lifestyle factors was developed and validated for high-risk early colorectal neoplasm among the Chinese population. This risk-based model could improve the pre-selection for screening and contribute a lot to efficient population-based screening in low-resource countries.

13.
Medicine (Baltimore) ; 100(5): e24332, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592878

RESUMO

ABSTRACT: Coronavirus disease 2019 (COVID-19) becomes a global pandemic in 2020. Early identification of severe ill patients is a top priority for clinicians. We aimed to describe clinical features and risk factors of severe-critically ill patients with COVID-19 in Jiangsu Province.This multi-centered retrospective study collected the information of 631 laboratory-confirmed COVID-19 patients hospitalized at 28 authorized hospitals in Jiangsu province from January 23, 2019 to March 13, 2020.A total of 583 adult patients with laboratory-confirmed COVID-19 were enrolled for final analysis, including 84 severe-critically ill patients and 499 mild-moderate patients. Median age of the severe-critically ill patients was 57.0 years old (interquartile range, 49.0-65.8), and 50 (59.5%) were males. Multisystemic laboratory abnormalities were observed on admission for severe-critically ill patients. These patients showed more noticeable radiologic abnormalities and more coexisting health issues as compared to the mild-moderate patients. Most of the severe-critically ill COVID-19 patients became deteriorated in 2 weeks after diagnosis. Age, D-dimer, and lymphocytes were independently associated with the progression of severe-critically illness.Older age, higher D-dimer levels and less lymphocyte counts on admission are potential risk factors for COVID-19 patients to develop into severe and critically illness.


Assuntos
COVID-19 , Estado Terminal/terapia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Contagem de Linfócitos , SARS-CoV-2 , Avaliação de Sintomas/estatística & dados numéricos , Fatores Etários , COVID-19/sangue , COVID-19/fisiopatologia , China/epidemiologia , Progressão da Doença , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Contagem de Linfócitos/métodos , Contagem de Linfócitos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença
14.
Nutr Metab (Lond) ; 17: 63, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774441

RESUMO

BACKGROUND: Hypertriglyceridemic waist (HTGW) phenotype has been suggested as a risk factor for chronic kidney disease (CKD). However, there is limited evidence on the relationship of triglyceride waist phenotypes with estimated glomerular filtration rate (eGFR) status and severity. Our aim was to explore the associations of triglyceride waist phenotypes with reduced eGFR and various decreased eGFR stages among Chinese adults. METHODS: A population-based, cross-sectional study was conducted among Chinese participants aged 20-74 years from June 2016 to December 2017 in Shanghai, China. An eGFR value below 60 mL/min/1.73 m2 was defined as decreased eGFR. HTGW phenotype was defined as triglyceride (TG) ≥1.7 mmol/L and a waist circumference (WC) of ≥90 cm for men and ≥ 80 cm for women. We examined the association of triglyceride waist phenotypes with decreased eGFR risk using the weighted logistic regression models. RESULTS: A total of 31,296 adults were included in this study. Compared with normal TG level/normal WC (NTNW) phenotype, normal TG level/enlarged WC (NTGW) and elevated TG level/enlarged WC (HTGW) phenotypes were associated with the increased risk of decreased eGFR. Multivariable-adjusted ORs (95% CI) associated with NTGW, elevated TG level/normal WC (HTNW), and HTGW phenotypes were 1.75 (1.41-2.18), 1.29 (0.99-1.68), and 1.99 (1.54-2.58), respectively. These associations between triglyceride waist phenotypes and decreased eGFR risk remained across almost all the subgroups, including sex, age, BMI, T2DM, and hypertension. HTGW phenotype was consistently positively associated with the risk of mildly and moderately decreased eGFR, but not with severely decreased eGFR risk. CONCLUSIONS: HTGW was consistently associated with the increased risk of decreased eGFR and various decreased eGFR stages, except for severely decreased eGFR. Further prospective studies are warranted to confirm our findings and to investigate the underlying biological mechanisms.

15.
BMJ Open ; 10(7): e035430, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641326

RESUMO

PURPOSE: The Shanghai Suburban Adult Cohort and Biobank (SSACB) was established to identify environmental, lifestyle and genetic risk factors for non-communicable chronic diseases (NCDs) in adults (20-74 years old) living in a suburban area of Shanghai with rapid urbanisation. PARTICIPANTS: Two of eight suburban district were purposely selected according to participant willingness, health service facilities, population, geographic region and electronic medical record system. From these suburban districts, four communities were selected based on economic level and population size. At stage three, one-third of the committees/villages were randomly selected from each community. All residents aged 20-74 years old were invited as study participants. FINDINGS TO DATE: The baseline data on demographics, lifestyle and physical health-related factors were collected using a face-to-face questionnaire interview. All participants completed physical examinations and had blood and urine tests. Blood and urine samples from these tests were stored in a biobank. From 6 April 2016 through 31 October 2017, we conducted face-to-face interviews and clinical examinations in 44 887 participants: 35 727 from Songjiang District and 9160 from Jiading District. The average age of participants was 56.4±11.2 years in Songjiang and 56.6±10.5 years in Jiading. The prevalence of hypertension, diabetes and dyslipidaemia was 34.0%, 8.2% and 11.1%, respectively. FUTURE PLANS: In-person surveys will be conducted every 5 years. For annual tracking, baseline data was linked to the local health information system, which was composed of an electronic medical record system, a chronic disease management system, a cancer registry system, an infectious disease report system and a death registry system. The data of the SSACB cohort is located in the School of Public Health, Fudan University. International and domestic collaborative research projects are encouraged and inherent in the project.


Assuntos
Protocolos Clínicos , Inquéritos e Questionários/normas , Estudos de Coortes , Humanos , Entrevistas como Assunto/métodos
16.
Sci Rep ; 10(1): 12946, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32719379

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

17.
Pathol Res Pract ; 216(2): 152795, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31879047

RESUMO

BACKGROUND: Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has a broad range of biological properties, including antitumor activity. However, the mechanisms by which DHA affects the tumorigenesis of gastric carcinoma (GC) are poorly understood. MATERIAL AND METHODS: The targets of DHA were identified by network pharmacology, and the association of CDK4 with clinicopathological characteristics and prognosis in patients with GC was analyzed by using TCGA data. CCK8, Transwell and flow cytometric analyses, as well as a tumor xenograft model, were used to assess the effects of DHA on the growth and migration of GC cells. qRT-PCR and Western blot analyses were used to determine the effects of DHA on the cyclin D1-CDK4-Rb signaling pathway. RESULTS: We identified 13 DHA targets and measured their expression of whichCDK4 expression levels were substantially higher in GC tissues than those in adjacent normal tissues, and high CDK4 expression acted as an independent prognostic factor of poor survival in patients with GC. DHA suppressed cell proliferation, migration and invasion in vitro and in vivo and induced G1 phase cell cycle arrest in a dose-dependent manner by regulating cyclin D1-CDK4-Rb signaling. CONCLUSIONS: DHA inhibits the tumorigenesis and invasion of GC by regulating cyclin D1-CDK4-Rb signaling and may provide therapeutic strategies for the treatment of GC.


Assuntos
Artemisininas/farmacologia , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Animais , Artemisininas/química , Carcinogênese/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Quinase 4 Dependente de Ciclina/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/prevenção & controle , Prognóstico , Estômago/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Qual Life Res ; 29(4): 1055-1064, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31782018

RESUMO

OBJECTIVE: To estimate the prevalence of poor sleep and its risk factors for adults living in a suburban area of Shanghai with rapid urbanization. METHODS: A total of 37,545 residents who were aged 20 to 74 years and from the "Peak Program," a community-based natural population cohort study, were included. Data on demographics, lifestyle, and physical health-related factors were collected using a face-to-face questionnaire interview. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and poor sleep was defined as a PSQI score above 7. RESULTS: The overall mean of PSQI score was 3.69 ± 2.57 while the prevalence of poor sleep was 8.3%. The prevalence of poor sleep quality was higher in participants who were older than 40 years, had less education, smoked tobacco, had anxiety, and had a chronic disease (p < 0.05 for all comparisons). After adjustment for confounding, a logistic regression model indicated that poor sleep was associated with advanced age, smoking, anxiety, cardiovascular and cerebrovascular diseases, respiratory diseases, and other chronic diseases (p < 0.05 for all comparisons). In addition, compared to women who were premenopausal, the naturally postmenopausal women (OR 1.675, 95% CI 1.44-1.94) and induced menopausal women (OR 2.26, 95% CI 1.81-2.82) were more likely to report poor sleep. CONCLUSION: The prevalence of poor sleep among individuals who lived in the Songjiang District of Shanghai and were aged 20 to 74 years was remarkably lower than in the general population of China. Poor sleep was generally more common in middle-aged and elderly residents and in those suffering from anxiety and chronic diseases. Regular exercise, anxiety relieving, and treatment improvement of different chronic diseases may help sleep better.


Assuntos
Distúrbios do Início e da Manutenção do Sono/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Sono/fisiologia , Adulto , Idoso , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Doenças Cardiovasculares/complicações , Transtornos Cerebrovasculares/complicações , China/epidemiologia , Doença Crônica , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Menopausa/fisiologia , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida/psicologia , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/psicologia , Transtornos do Sono-Vigília/psicologia , Fumantes/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
19.
Ann Nutr Metab ; 75(3): 168-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31739307

RESUMO

BACKGROUND/AIMS: Metabolic syndrome (MetS) and its metabolic components, the common risk factors, may be involved in the development and progression of decreased estimated glomerular filtration rate (eGFR). The aim of this study was to examine the association of MetS and its metabolic components with eGFR status and severity among Chinese adults. METHODS: The population-based, cross-sectional study recruited a total of 33,300 Chinese adults (aged ≥18 years) from 4 study community sites in Songjiang District, Shanghai, between June 2016 and December 2017. Decreased eGFR was defined as a value of eGFR below 60 mL/min/1.73 m2. Weighted multiple logistic regression models were used to examine the association of MetS and its components with eGFR status and severity. RESULTS: After adjusting for potential confounders, subjects with MetS had an increased risk of decreased eGFR with an adjusted OR of 1.76 (95% CI 1.53-2.01), and subjects with increasing numbers of MetS components had a gradually increased risk for decreased eGFR (p trend <0.001). The multivariable-adjusted ORs (95% CI) of decreased eGFR were 1.66 (1.44-1.93) for abdominal obesity, 1.37 (1.18-1.60) for elevated triglycerides, 1.13 (0.96-1.33) for reduced high-density lipoprotein cholesterol, 0.84 (0.72-0.98) for elevated fasting glucose, and 1.92 (1.57-2.35) for elevated blood pressure (BP). Furthermore, these associations remained in most of the subgroups analyses. Significant associations between elevated BP and the risks of mildly, moderately, and severely decreased eGFR were also found. CONCLUSIONS: MetS was independently associated with an increased risk of decreased eGFR, and individual components of MetS each play a different role in decreased eGFR. Elevated BP may be an important risk factor for the progression of renal dysfunction or even chronic kidney disease.


Assuntos
Taxa de Filtração Glomerular , Síndrome Metabólica/complicações , Adulto , Idoso , Povo Asiático , Glicemia , China , HDL-Colesterol/sangue , Estudos Transversais , Registros Eletrônicos de Saúde , Feminino , Humanos , Hipertensão/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Fatores de Risco , Triglicerídeos/sangue
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