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1.
Mult Scler Relat Disord ; 51: 102870, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33819724

RESUMO

OBJECTIVE: Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease of the central nervous system. Glial fibrillary acidic protein (GFAP) is a monomeric intermediate filament protein. A systematic review and meta-analysis was performed regarding a candidate biomarker for astrocytic damage of cerebrospinal fluid (CSF) and blood GFAP levels in differentiating multiple sclerosis and its subtypes. METHODS: Relevant studies published prior to October 2020 were retrieved from the PubMed, Web of Science, Cochrane Library and clinicaltrials.gov databases using the following keywords: 'Multiple sclerosis' or 'MS' and 'Glial Fibrillary Acidic Protein' or 'GFAP'. Two authors independently selected the articles and extracted the data. Of the 31 full articles screened, 11 were included in the qualitative analysis and meta-analysis. Differences in the mean CSF and blood GFAP levels were used as the main efficacy measures, and the meta-analysis was performed using Review Manager version 5.3 software. RESULTS: Eleven clinical trials comprising 960 patients were selected. CSF GFAP levels were higher in 503 MS patients than in 252 (healthy and disease) controls, with a moderate effect size of 0.72 (p < 0.00001). Mean CSF GFAP levels were significantly higher in 325 MS patients with relapsing disease than in 140 MS patients with progressive disease (SMD=-0.47; 95% CI=-0.80 to -0.15; P = 0.005). CSF GFAP levels in 161 MS patients in relapse (irrespective of MS subtype) were significantly higher than those in 180 MS patients in remission (MD=103.83; 95% CI=68.09 to139.57; P<0.001). The performances of GFAP in blood for differentiating patients with MS from controls were also significant. Blood GFAP was higher in 245 MS patients than in 53 (healthy and disease) controls, with a moderate effect size of 37.25 (p < 0.00001). CONCLUSION: The level of CSF-GFAP is correlated with MS and its different subtypes, reflecting the different degrees of damage to astrocytes in different subtypes of MS. In addition, progressive MS is more closely related to the increase in cerebrospinal fluid GFAP level than relapsing-remitting MS, and GFAP may be a useful marker of disease progression. Moreover, the GFAP level in the blood of MS patients is higher than that in the control group, and the sample size needs to be further expanded for verification in the future..

2.
BMC Genomics ; 22(1): 272, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858332

RESUMO

BACKGROUND: Human cancer cell line profiling and drug sensitivity studies provide valuable information about the therapeutic potential of drugs and their possible mechanisms of action. The goal of those studies is to translate the findings from in vitro studies of cancer cell lines into in vivo therapeutic relevance and, eventually, patients' care. Tremendous progress has been made. RESULTS: In this work, we built predictive models for 453 drugs using data on gene expression and drug sensitivity (IC50) from cancer cell lines. We identified many known drug-gene interactions and uncovered several potentially novel drug-gene associations. Importantly, we further applied these predictive models to ~ 17,000 bulk RNA-seq samples from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database to predict drug sensitivity for both normal and tumor tissues. We created a web site for users to visualize and download our predicted data ( https://manticore.niehs.nih.gov/cancerRxTissue ). Using trametinib as an example, we showed that our approach can faithfully recapitulate the known tumor specificity of the drug. CONCLUSIONS: We demonstrated that our approach can predict drugs that 1) are tumor-type specific; 2) elicit higher sensitivity from tumor compared to corresponding normal tissue; 3) elicit differential sensitivity across breast cancer subtypes. If validated, our prediction could have relevance for preclinical drug testing and in phase I clinical design.

3.
Signal Transduct Target Ther ; 6(1): 108, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33664238

RESUMO

Alternative splicing is a critical process to generate protein diversity. However, whether and how alternative splicing regulates autophagy remains largely elusive. Here we systematically identify the splicing factor SRSF1 as an autophagy suppressor. Specifically, SRSF1 inhibits autophagosome formation by reducing the accumulation of LC3-II and numbers of autophagosomes in different cell lines. Mechanistically, SRSF1 promotes the splicing of the long isoform of Bcl-x that interacts with Beclin1, thereby dissociating the Beclin1-PIK3C3 complex. In addition, SRSF1 also directly interacts with PIK3C3 to disrupt the interaction between Beclin1 and PIK3C3. Consequently, the decrease of SRSF1 stabilizes the Beclin1 and PIK3C3 complex and activates autophagy. Interestingly, SRSF1 can be degraded by starvation- and oxidative stresses-induced autophagy through interacting with LC3-II, whereas reduced SRSF1 further promotes autophagy. This positive feedback is critical to inhibiting Gefitinib-resistant cancer cell progression both in vitro and in vivo. Consistently, the expression level of SRSF1 is inversely correlated to LC3 level in clinical cancer samples. Our study not only provides mechanistic insights of alternative splicing in autophagy regulation but also discovers a new regulatory role of SRSF1 in tumorigenesis, thereby offering a novel avenue for potential cancer therapeutics.

4.
BMC Public Health ; 21(1): 512, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726744

RESUMO

BACKGROUND: Physical activity has many health benefits for children and adolescents. However, the prevalence of physical inactivity in school-aged children and adolescents remains high in China. Many factors impact the levels of moderate and vigorous physical activity (MVPA) among students. This study investigated the factors associated with students' MVPA levels and the determinants of changes in their MVPA behaviour. METHODS: This is a longitudinal study with a 12-month follow-up. The study samples were obtained from 2016 and 2017 Physical Activity and Fitness in China-The Youth Study, and they included 1597 students (aged 9-18 years) from 31 primary, junior high, and high schools in Ningxia Province. Factors related to the individual (Age, Sex, BMI and attitude to PA), school (school exercise facility, PE class, teacher support, PA time and PA environment) and neighbourhood (free skill training, sport events, sport organization, sport facility) factors were measured via questionnaire at baseline and after 12 months. Multiple logistic regression was performed to examine the factors that impact students' MVPA level and the determinants of changes in students' MVPA behaviour. RESULTS: There was no difference in students' MVPA levels between 2016 and 2017. Boys were more physically active than girls at baseline (RR 1.55, 95% CI 1.10, 2.20). Neighbourhood factors associated students' MVPA levels were significant, but all of these factors (neighbourhood sport events, organizations, facilities, etc.) were removed from the longitudinal model. Individual and school factors were important for students' MVPA maintenance and positive development (e.g., gender, attitude, school PE class and PA time). CONCLUSIONS: In conclusion, both neighbourhood and school factors may affect students' MVPA, but school appears to plays a more critical role in maintaining and promoting students' MVPA levels. In addition, individual factors may be more important than school and neighbourhood factors in influencing students' MVPA levels. Our research demonstrates that students' attitudes towards PA and school factors should be considered targets for future intervention programmes to promote MVPA. More education programmes may help enhance students' attitudes towards PA, but more studies with large samples and objective assessments are needed to explore the determinants of MVPA.

5.
J Exp Clin Cancer Res ; 40(1): 81, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648534

RESUMO

Single-cell RNA sequencing (scRNA-seq), a technology that analyzes transcriptomes of complex tissues at single-cell levels, can identify differential gene expression and epigenetic factors caused by mutations in unicellular genomes, as well as new cell-specific markers and cell types. scRNA-seq plays an important role in various aspects of tumor research. It reveals the heterogeneity of tumor cells and monitors the progress of tumor development, thereby preventing further cellular deterioration. Furthermore, the transcriptome analysis of immune cells in tumor tissue can be used to classify immune cells, their immune escape mechanisms and drug resistance mechanisms, and to develop effective clinical targeted therapies combined with immunotherapy. Moreover, this method enables the study of intercellular communication and the interaction of tumor cells and non-malignant cells to reveal their role in carcinogenesis. scRNA-seq provides new technical means for further development of tumor research and is expected to make significant breakthroughs in this field. This review focuses on the principles of scRNA-seq, with an emphasis on the application of scRNA-seq in tumor heterogeneity, pathogenesis, and treatment.

6.
Sci Rep ; 11(1): 4901, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649481

RESUMO

Fucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties. However, the effects and underlying molecular mechanism of fucosterol on non-small cell lung cancer remain to be elucidated. In this study, the corresponding targets of fucosterol were obtained from PharmMapper, and NSCLC related targets were gathered from the GeneCards database, and the candidate targets of fucosterol-treated NSCLC were predicted. The mechanism of fucosterol against NSCLC was identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data were collected from STRING database. The hub gene GRB2 was further screened out and verified by molecular docking. Moreover, the relationship of GRB2 expression and immune infiltrates were analyzed by the TIMER database. The results of network pharmacology suggest that fucosterol acts against candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8, and SRC, which regulate biological processes including negative regulation of the apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf/MEK/ERK signaling pathway initiated by GRB2 showed to be significant in treating NSCLC. In conclusion, our study indicates that fucosterol may suppress NSCLC progression by targeting GRB2 activated the Raf/MEK/ERK signaling pathway, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33650273

RESUMO

PURPOSE: Metformin is widely used as an insulin sensitizer in polycystic ovary syndrome (PCOS) patients. However, previous studies have found that the effect of metformin on the level of homocysteine were not consistent in PCOS patients. The aim of this review was to analyze the effect of metformin on homocysteine levels in patients with PCOS patients. METHODS: The Cochrane Library, Pubmed, and Web of Science were searched according to predefined search terms. There is no restriction for publication time and language. RESULTS: Eleven studies were included and the data were extracted. The homocysteine level in PCOS patients was significantly increased after taking metformin (mean difference [MD] -1.33; 95% confidence interval [CI] -2.16 to -0.49, p = 0.002). Subgroup analysis showed that the level of homocysteine was generally increased in PCOS patients with body mass index (BMI) ≥25 after taking metformin alone (MD -1.82; 95% CI -2.56 to -1.07, p < 0.00001). There was no significant change in homocysteine level in PCOS patients with BMI <25 (MD 0.69; 95% CI -0.41 to 1.79, p = 0.22). Subgroup analysis showed that there was no significant difference when taking metformin >3 months or taking metformin ≤3 months (p = 0.84). Taking metformin ≥1700 mg/days significantly increased homocysteine levels in PCOS patients (MD -2.05; 95% CI -2.40 to -1.70, p < 0.00001). When taking metformin <1700 mg/days, there was no significant difference in homocysteine level in PCOS patients (MD 0.15; 95% CI -1.06 to 1.37, p = 0.80). The difference between the two subgroups was significant (p = 0.0006). There was no significant difference in vitamin B12 level before and after metformin treatment (MD 24.70; 95% CI -22.54 to 71.93, p = 0.31). There was a decrease in serum folic acid level after metformin administration (MD 1.03; 95% CI 0.80 to 1.26, p < 0.00001). CONCLUSION: Taking metformin alone increased homocysteine levels and decreased folic acid levels in nonpregnant PCOS patients. And, it was suggested that the dosage of metformin should be less than 1700 mg/days. The supplement of folic acid and B vitamins during metformin administration may be essential in nonpregnant PCOS patients. We should pay much attention to the potential effect of metformin in PCOS patients.

8.
Medicine (Baltimore) ; 100(9): e24829, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655944

RESUMO

ABSTRACT: An increasing number of studies focus on the effectiveness of Massive Open Online Courses (MOOC)-based blended learning, whereas none have yet studied using it for teaching fundamental nursing skills at an undergraduate level.To evaluate the effectiveness of MOOC-based blended learning versus face-to-face classroom teaching techniques within the fundamental nursing course at the Faculty of Nursing, University of Xiang Nan, China.This cluster randomized controlled trial enrolled 181 students and assigned them into either an MOOC-based blended or a face-to-face classroom teaching group, both involving the Fundamental Nursing course for undergraduate nursing students. The analyzed outcomes included test scores, critical thinking ability, and feedback received from the students on the Fundamental Nursing course.MOOC-based blended techniques versus face-to-face classroom teaching methods demonstrated higher daily performance (P = .014), operational performance (P = .001), theoretical achievements (P < .001), and final grades (P < .001) in Fundamental Nursing.Moreover, the mean change in the participants' critical thinking ability items between groups were, mostly, statistically significant. The items focusing on the feedback from the students demonstrated significant differences between the groups in terms of their satisfaction with the teaching they received (P < .001) and the overall learning effects (P = .030).This study confirmed that receiving MOOC-based blended learning was superior when compared against face-to-face classroom teaching techniques for learning within the Fundamental Nursing course.


Assuntos
Currículo , Educação a Distância/métodos , Bacharelado em Enfermagem/métodos , Avaliação Educacional/métodos , Internet , Aprendizagem Baseada em Problemas/métodos , Ensino/organização & administração , China , Instrução por Computador/métodos , Feminino , Humanos , Masculino , Adulto Jovem
9.
Biol Reprod ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33675651

RESUMO

OBJECTIVE: To investigate the pathophysiological significance of Par3 and integrin ß1 with regards to the functionality of the endometrial luminal epithelium (LE). DESIGN: Laboratory study. SETTING: University research laboratory. PATIENTS: Analysis involved endometrial aspirates and human endometrial epithelial cells (HEC-1A cells and RL95-2 cells). INTERVENTIONS: We first examined the expression and localization of Par3 and integrin ß1 in HEC-1A cells and RL95-2 cells. Then we knocked down Par3 and integrin ß1 in HEC-1A cells and RL95-2 cells respectively and found that Par3/integrin ß1 affected embryo adhesion by regulating the intercellular tight junctions (TJs) structure and thus the polarity of endometrial LE. These findings were also confirmed in endometrium specimens from human and mice. MAIN OUTCOME MEASURES: The expression and localization of Par3 and integrin ß1 in endometrial epithelial cell lines and endometrium specimens. The regulations of Par3 and integrin ß1 on TJs, polarity and embryo adhesion. RESULTS: Following the knockdown of Par3 in HEC-1A cells, there was a reduction in the complexity of the TJs and cell polarity, and the adhered blastocysts number was significantly increased. However, the reduction of integrin ß1 in RL95-2 cells resulted in effects that directly opposed those following the knockdown of Par3 in HEC-1A cells. Estrogen and progesterone reduced the expression of Par3 and promoted the expression of integrin ß1 in HEC-1A cells. CONCLUSIONS: Par3/integrin ß1 regulates embryo adhesion by regulating intercellular TJs structure and polarity of endometrial LE under the action of ovarian hormones.

10.
Aging (Albany NY) ; 13(4): 4811-4830, 2021 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-33581688

RESUMO

Traditional Chinese medicine (TCM) had demonstrated effectiveness in the prevention and control of COVID-19. Statistics showed that Ephedra and Glycyrrhiza were frequently used in the treatment of COVID-19. We hypothesized that the Ephedra-Glycyrrhiza drug pair is a potential choice for the treatment of COVID-19. Here, 112 active compounds were identified from Ephedra-Glycyrrhiza via network pharmacology approach. Ephedra-Glycyrrhiza pair enrichment analysis demonstrated that these compounds might participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signaling pathways, which had a high correlation with respiratory, nervous, blood circulation and digestive system-related diseases. Pathway analysis between Ephedra-Glycyrrhiza and COVID-19 showed that the key targets were TNF-α, IL2, FOS, ALB, and PTGS2. They might control PI3K-Akt signaling pathway to exert immune regulation, organ protection and antiviral effects. Molecular docking results showed that the active compounds from the Ephedra-Glycyrrhiza pair bound well to COVID-19 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). The Molecular dynamics simulation was analyzed for the stability and flexibility of the complex. In conclusion, our study elucidated the potential pharmacological mechanism of Ephedra-Glycyrrhiza in the treatment of COVID-19 through multiple targets and pathways.


Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ephedra/química , Glycyrrhiza/química , /efeitos dos fármacos , /metabolismo , Antivirais/química , Antivirais/uso terapêutico , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo
11.
Brain Behav ; 11(4): e02057, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33560579

RESUMO

OBJECTIVE: The study aimed to explore the cerebral areas with changes in regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) values induced by effective acupuncture on the Taibai (SP3) point. METHODS: In the study, 15 healthy right-handed volunteers (seven males and eight females, 20-35 years old) were enrolled. The average ages of the subjects were 28.0 ± 4.24 years for males and 27.4 ± 3.65 years for females. A 3.0T magnetic resonance imaging (MRI) system was used to perform resting-state functional MRI scan after sham and effective acupuncture on the SP3 point. The differences in cerebral ReHo and ALFF values between posteffective acupuncture and postsham acupuncture were compared using the SPM 12 software. RESULTS: ReHo values of bilateral BA18, cuneus, and BA17, along with BA41, BA22, postcentral gyrus, and BA7 on the right side, were decreased by effective SP3 acupuncture. The ALFF values of bilateral BA 30 and left parahippocampal area were increased, whereas the values of bilateral BA18, BA19, cuneus, posterior cingulate gyrus, and BA7, along with the right superior occipital lobule, postcentral gyrus, and left precuneus, were decreased. CONCLUSIONS: The most dominant cerebral areas affected by SP3 acupuncture were bilateral visual-related cortices (lingual gyrus, cuneus, and calcarine), along with the unilateral postcentral gyrus and superior parietal lobule. These findings may be potential explanations for the available clinical reports concerning the efficacy of SP3 acupuncture. Further clinical and experimental studies on SP3 acupuncture are required.

12.
Clin Biochem ; 90: 50-57, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33539806

RESUMO

BACKGROUND: Parathyroid hormone (PTH) and vitamin D plays a major role in calcium (Ca) homeostasis and bone turnover. The purpose of this study was to assess which factors (sex, age, time of blood sampling, season of the year, temperature and sunshine hours (SHH)) had the greatest impact on plasma PTH, 25-OH-VitD, and Ca levels, and then whether these effects were clinically acceptable in a large number of Southwestern Chinese subjects. METHOD: The data was from West China Hospital Health Examination Center, Sichuan University from April 1, 2018 to June 30, 2019. A total of 18,664 physical examination subjects were included. PTH and 25-OH-VitD were measured by a Roche Cobas e 601, and Ca was measured by a Roche Cobas 8000. Linear regression models were used to assess correlations between PTH, 25-OH-VitD, Ca and the above factors. RESULTS: The concentrations of serum PTH in females were significantly higher than those in males, while the 25-OH-VitD and Ca were opposite. The concentration of PTH in data collection decreased in summer and increased in spring. The concentration of 25-OH-VitD decreases in spring and increases in autumn. PTH concentrations were negatively correlated with last month temperature and SHH, while 25-OH-VitD were opposite. Linear regression showed that season may be the main factor affecting serum PTH and 25-OH-VitD levels, and these effects were not clinically acceptable. CONCLUSION: In order to avoid influencing clinicians' investigation of suspected hyperparathyroidism and hypovitaminosis, reference intervals for PTH, 25-OH-VitD, and Ca should be established, taking into account sex, age and the season.

13.
Sci Total Environ ; 775: 145777, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-33631593

RESUMO

BACKGROUND: Few studies have explored the short-term effects of ultrafine particles (UFPs, particles < 0.1 µm) air pollution on the exacerbations of pediatric respiratory diseases. OBJECTIVES: We aimed to evaluate short-term association between UFP and emergency-department visits (EDVs) for main pediatric respiratory diseases. METHODS: We collected daily data on UFP and pediatric EDVs for main respiratory diseases [asthma, pneumonia, bronchitis and upper respiratory tract infections (URTI)] from 66 hospitals in Shanghai, China from 2016 to 2018. Generalized additive models combined with polynomial distributed lag models were applied to explore the associations between UFP level and pediatric EDVs for respiratory diseases. We fitted two-pollutant models with criteria air pollutants and performed stratified analyses by gender and age. RESULTS: UFP was associated with increased EDVs for all respiratory diseases in cumulative lags up to 2 d and 3 d. The greatest risk was found at cumulative lags (0-2 d) for all respiratory diseases. At cumulative lags (0-2 d), an interquartile range increase in concentrations of UFP (1800 particles/cm3) was associated with relative risks of EDVs due to asthma [1.35, 95% confidence interval (CI): 1.14-1.59], pneumonia (1.20, 95% CI: 1.04-1.38), bronchitis (1.17, 95% CI: 1.03-1.33) and URTI (1.14, 95% CI: 1.02-1.28). These associations were almost unchanged when controlling for criteria air pollutants, and there was no threshold below which the associations were not present. There were stronger associations in children aged 0-13 years. CONCLUSIONS: Short-term exposure to UFP may independently increase the risks of EDVs for asthma, pneumonia, bronchitis and URTI exacerbations among children.

14.
Hu Li Za Zhi ; 68(1): 43-53, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33521918

RESUMO

BACKGROUND: Because of the COVID-19 epidemic, people are mostly isolated at home and must seek medical advice over the internet. In addition, government authorities are currently investing greater efforts in developing internet hospitals. PURPOSE: The purpose of this essay was to assess how outpatients feel about online outpatient clinics and to analyze the factors that affect their satisfaction and willingness to return to these clinics. The results provide advice regarding how to more effectively encourage patients to use online outpatient clinics. METHODS: A self-developed questionnaire was used to survey 191 patients who had visited the online outpatient clinic of a tertiary hospital in Sichuan Province from January to July 2019. A descriptive analysis was conducted on the collected data, and factors influencing satisfaction were identified. RESULTS: The majority of the surveyed patients were young or middle-aged (92.7%) and 42.9% held a college degree or higher. Nearly three-quarters (72.2%) expressed feeling satisfied or better with the online outpatient clinic, with 31.4% of these expressing feeling very satisfied. Nearly all (91.1%) expressed the opinion that the online outpatient clinic had improved their awareness of health self-management . Furthermore, 176 (92.1%) were willing to use the online outpatient clinic again. The results of univariate analysis showed that the main factors negatively influencing re-use of the online outpatient clinic were: failure to solve the problem in a timely manner (χ2 = 8.603, p = .045), the complicated process of online registration (χ2 = 8.322, p = .016), the failure of the online physical examination (χ2 = 8.958, p = .015), and unreliable quality (χ2 = 15.373, p = .004). CONCLUSIONS: The participants surveyed in this study reported a lower satisfaction for their online outpatient clinic experience than reported in similar surveys of traditional outpatient services. However, many reported that their health-related self-management awareness had improved after use, indicating that they feel better about the online outpatient clinic. The factors that affected willingness to reuse to the online outpatient clinic related mainly to imperfections related to the clinic and its inability to adequately meet patient needs. Online outpatient clinics should simplify the process of registration, improve functions, and increase service functions such as online examination appointments and follow-up visits to improve patient satisfaction.


Assuntos
Idoso , Instituições de Assistência Ambulatorial , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Retratamento , Inquéritos e Questionários
15.
Mol Cancer ; 20(1): 7, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397409

RESUMO

BACKGROUND: Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. MAIN BODY: In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. CONCLUSION: Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

16.
Cell Stem Cell ; 28(4): 748-763.e7, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33450185

RESUMO

Histone crotonylation is a non-acetyl histone lysine modification that is as widespread as acetylation. However, physiological functions associated with histone crotonylation remain almost completely unknown. Here we report that histone crotonylation is crucial for endoderm differentiation. We demonstrate that key crotonyl-coenzyme A (CoA)-producing enzymes are specifically induced in endodermal cells during differentiation of human embryonic stem cells (hESCs) in vitro and in mouse embryos, where they function to increase histone crotonylation and enhance endodermal gene expression. Chemical enhancement of histone crotonylation promotes endoderm differentiation of hESCs, whereas deletion of crotonyl-CoA-producing enzymes reduces histone crotonylation and impairs meso/endoderm differentiation in vitro and in vivo. Our study uncovers a histone crotonylation-mediated mechanism that promotes endodermal commitment of pluripotent stem cells, which may have important implications for therapeutic strategies against a number of human diseases.

17.
Cancer Lett ; 496: 41-56, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931883

RESUMO

An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in malignant tumor initiation and progression; however, many circRNAs are yet unidentified, and the role of circRNAs in nasopharyngeal carcinoma (NPC) is unclear. Using RNA sequencing, we discovered a novel circRNA, termed circARHGAP12, that was processed from the pre-mRNA of the ARHGAP12 gene. CircARHGAP12 was significantly upregulated in NPC tissues and cell lines and promoted NPC cell migration and invasion. Overexpression or knockdown experiments revealed that circARHGAP12 regulates the expression of cytoskeletal remodeling-related proteins EZR, TPM3, and RhoA. CircARHGAP12 was found to bind directly to the 3' UTR of EZR mRNA and promote its stability; moreover, EZR protein interacted with TPM3 and RhoA and formed a complex to promote NPC cell invasion and metastasis. This study identified the novel circRNA circARHGAP12, characterized its biological function and mechanism, and increased our understanding of circRNAs in NPC pathogenesis. In particular, circARHGAP12 was found to promote the malignant biological phenotype of NPC via cytoskeletal remodeling, thus providing a clue for targeted therapy of NPC.

18.
Biomed Pharmacother ; 132: 110945, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254439

RESUMO

Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) -stimulator of interferon genes (STING) signaling pathway is the primary immune response pathway in the cytoplasm. Pharmacological regulation of the STING pathway has good characteristics in both structure and function, which plays a significant role in the immunotherapy of autoimmune diseases, autoinflammatory diseases, and cancer. In this review, we summarized the activation of STING signaling pathway, the STING-related diseases, the development principle and the latest progress of inhibitors and agonists targeting STING. Our review demonstrates that STING signal pathway is a promising drug target, providing effective clues and correct guidance for the discovery of novel small molecule inhibitors/agonists that targeted STING for cancer, autoimmune, and inflammatory diseases.

19.
J Thorac Dis ; 12(11): 6466-6475, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33282349

RESUMO

Background: To explore the feasibility of using quantitative high-resolution computed tomography (HRCT) to evaluate pulmonary function in patients with pulmonary lymphangioleiomyomatosis (PLAM). Methods: Pulmonary function tests (PFTs) were performed in 30 patients with pathologically confirmed PLAM with the use of HRCT. These results were correlated with quantitative HRCT in 21 patients. Results: There were significant correlations between the HRCT parameters for lung function and PFT parameters. Among these parameters, emphysema volume (EV), pulmonary volume with a pixel index less than the trigger threshold (-950 HU) to account for a proportion of total lung volume [PI-950 (%)] and forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC (%)] had the strongest correlations, reaching values between -0.71 and -0.68. HRCT lung function might therefore also be helpful for predicting changes in lung function before and after treatment. Conclusions: HRCT is helpful for the assessment of pulmonary function in PLAM patients and can assist in the clinical evaluation of lung function and treatment response in patients with this disease.

20.
Cancer Cell Int ; 20(1): 561, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33292235

RESUMO

BACKGROUND: EGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of EGFR mutated NSCLC. Parthenolide, a natural product of parthenolide, which belongs to the sesquiterpene lactone family and has a variety of biological and therapeutic activities, including anti-cancer effects. However, its effect on non-small cell lung cancer is little known. METHODS: The CCK8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell apoptosis. In silico molecular docking was used to evaluate the binding of parthenolide to EGFR. Network pharmacology analysis was was used to evaluate the key gene of parthenolide target NSCLC. Western blotting was used to evaluate the key proteins involved apoptosis and EGFR signalling. The effect of parthenolide treatment in vivo was determined by using a xenograft mouse model. RESULTS: In this study, parthenolide could induce apoptosis and growth inhibition in the EGFR mutated lung cancer cells. Parthenolide also reduces the phosphorylation of EGFR as well as its downstream signaling pathways MAPK/ERK and PI3K/Akt. Molecular docking analysis of EGFR binding site with parthenolide show that the anti-cancer effect of parthenolide against NSCLC is mediated by a strong binding to EGFR. Network pharmacology analysis show parthenolide suppresses NSCLC via inhibition of EGFR expression. In addition, parthenolide inhibits the growth of H1975 xenografts in nude mice, which is associated with the inhibition of the EGFR signaling pathway. CONCLUSIONS: Taken together, these results demonstrate effective inhibition of parthenolide in NSCLC cell growth by targeting EGFR through downregulation of ERK and AKT expression, which could be promisingly used for patients carrying the EGFR mutation.

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