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1.
Cancer Med ; 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499228

RESUMO

The Kelch repeat and BTB domain containing 7 (KBTBD7) was first cloned in 2010. Its function as a transcriptional activator and a substrate adaptor during the ubiquitination process was soon found. KBTBD7 was shown to be involved in excessive inflammation after myocardial infarction, brain development, and neurofibromin stability. However, studies on the role of KBTBD7 in solid tumors, especially lung cancer, are still lacking. Therefore, in this study, we investigate the role of KBTBD7 in non-small cell lung cancer (NSCLC). Immunohistochemical staining of 104 paired NSCLC and peritumoral normal specimens indicated that KBTBD7 was highly expressed in NSCLC tissues and positively correlated with the histological type, P-TNM stage, lymph node metastasis, and tumor size. KBTBD7 was also well-expressed in NSCLC cell lines, and downregulation of KBTBD7 resulted in inhibition of NSCLC cell proliferation and invasion. Further investigation showed that KBTBD7 enhanced ubiquitin-dependent degradation of PTEN, thus activating EGFR/PI3K/AKT signaling and promoting NSCLC cell proliferation and invasion by regulating CCNE1, CDK4, P27, ZEB-1, Claudin-1, ROCK1, MMP-9, and E-cadherin protein levels. Our results indicate that KBTBD7 may be a potential therapeutic target for the treatment of NSCLC.

2.
Front Surg ; 9: 853363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548181

RESUMO

Objectives: The prognosis for stage I pulmonary adenocarcinoma is generally good. However, some patients with stage I pulmonary adenocarcinoma have an unexpectedly poor outcome. This warrants consideration of adjunct markers. In this study, we analyze carcinoembryonic antigen, Ki-67, and a pathologic subtype in combination for prognostic evaluation of stage I pulmonary adenocarcinoma. These factors were selected for study as they have been shown to be individually associated with prognosis in many studies. Methods: A total of 650 patients with stage I pulmonary adenocarcinoma were investigated retrospectively. Each patient was re-staged using standard TNM criteria. Carcinoembryonic antigen (CEA) values were obtained from preoperative blood samples, and Ki-67 was evaluated with tumor tissue immunohistochemistry. Patient clinicopathologic characteristics, survival status, and date of death were obtained from medical records and telephone follow-up. Results: CEA > 4.4 ng/ml, Ki-67 > 13%, and a solid-micropapillary tumor growth pattern were each independent adverse prognostic markers for 5-year disease specific survival in stage I pulmonary adenocarcinoma. However, in combination, these 3 factors yielded a prognostic value (designated "CEA-Ki-67-pathologic subtype" value). Stage I pulmonary adenocarcinoma of low-risk CEA-Ki-67-pathologic subtype (CKP) value show biologic behavior similar to TNM stage IA1 tumors, while stage I tumors of high-risk CKP value are similar in prognosis to TNM stage II. Conclusion: The CKP value may be used as an adjunct to the TNM classification, which may yield a more accurately defined prognosis for cases of stage I pulmonary adenocarcinoma. CKP value may identify patients at higher risk who may benefit from adjuvant chemotherapy. Conversely, lower risk CKP values may support avoidance of chemotherapy.

3.
Curr Med Sci ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35486298

RESUMO

OBJECTIVE: Gestational diabetes mellitus (GDM) and gestational weight gain (GWG) are important risk factors that are known to affect offspring growth, but these outcomes are inconsistent and it remains unknown if both risk factors have a synergetic effect on early childhood growth. The present study aimed to conduct offspring body mass index-for-age Z-scores (BMIZ) trajectories and to evaluate the independent and interactive effect of the status of GDM and excessive GWG on the risks of overweight/obesity from birth to 24 months of age. METHODS: A total of 7949 mother-child pairs were enrolled in this study. The weight and length of children were measured at birth, 6, 12, and 24 months of age to calculate BMIZ. RESULTS: The status of GDM was positively associated with offspring BMIZ and risk of macrosomia at birth but was not associated with offspring BMIZ or the risks of overweight/obesity at 6, 12, and 24 months of age. In contrast, excessive GWG was positively linked to offspring BMIZ, the stable high BMIZ trajectory pattern, and risks of overweight/obesity in the first 24 months of age. These two risk factors also had a significant synergistic effect on macrosomia at birth, but the interactive effect was only significant in boys during the follow-up years in the sex-stratified analyses. CONCLUSION: The maternal GWG was a more pronounced predictor than GDM with relation to BMIZ and risk of overweight/obesity in early childhood. The interactive effect between these risk factors on offspring overweight/obesity may vary by sex.

4.
Ecotoxicol Environ Saf ; 237: 113541, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35483144

RESUMO

Combined bioaugmentation inoculants composed of two or more plant growth-promoting bacteria (PGPB) were more effective than single inoculants for plant growth and cadmium (Cd) removal in contaminated soils. However, the principles of consortia construction still need to be discovered. Here, a pot experiment with Cd natural polluted soil was conducted and PGPB consortia with different ecological niches from hyperaccumulator Sedum alfredii Hance were used to compare their effects and mechanisms on plant growth condition, Cd phytoextraction efficiency, soil enzymatic activities, and rhizospheric bacterial community of Brassica juncea L. The results showed that both rhizospheric and endophytic PGPB consortia inoculants promoted plant growth (6.9%-22.1%), facilitated Cd uptake (230.0%-350.0%) of oilseed rape, increased Cd phytoextraction efficiency (343.0%-441.0%), and enhanced soil Cd removal rates (92.0%-144.0%). PGPB consortia inoculants also enhanced soil microbial carbon by 22.2%-50.5%, activated the activities of soil urease and sucrase by 74.7%-158.4% and 8.4%-61.3%, respectively. Simultaneously, PGPB consortia inoculants increased the relative abundance of Flavobacterium, Rhodanobacter, Kosakonia, Pseudomonas and Paraburkholderia at the genus level, which may be beneficial to plant growth promotion and bacterial phytopathogen biocontrol. Although the four PGPB consortia inoculants promoted oilseed growth, amplified Cd phytoextraction, and changed bacterial community structure in rhizosphere soil, their original ecological niches were not a decisive factor for the efficiency of PGPB consortia. therefore, the results enriched the present knowledge regarding the significant roles of PGPB consortia as bioaugmentation agents and preliminarily explored construction principles of effective bioaugmentation inoculants, which will provide insights into the microbial responses to combined inoculation in the Cd-contaminated soils.


Assuntos
Inoculantes Agrícolas , Sedum , Poluentes do Solo , Bactérias , Biodegradação Ambiental , Cádmio/análise , Mostardeira , Rizosfera , Sedum/microbiologia , Solo , Poluentes do Solo/análise
5.
Small ; 18(17): e2107838, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35333441

RESUMO

Treatment for spinal cord injuries (SCIs) is often ineffective because SCIs result in a loss of nerve tissue, glial scar formation, local ischemia and secondary inflammation. The current promising strategy for SCI is the combination of bioactive materials and cytokines. Bioactive materials support the injured spinal cord, stabilize the morphology, and avoid excessive inflammatory responses. Fat extract (FE) is a cell-free liquid component containing a variety of cytokines extracted from human fat tissue using mechanical methods. In this research, a biocompatible HAMC (hyaluronan and methylcellulose) loaded with FE is used to treat a model of spinal cord contusion in mice. The composite not only inhibits death of neuro- and vascular cells and leads to the preservation of neural and vascular structure, but also modulates the inflammatory phenotype of macrophages in the locally injured region. Specifically, FE promotes the polarization of macrophages from an inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. During the screening of the involved pathways, it is corroborated that activation of the STAT6/Arg-1 signaling pathway is involved in macrophage M2 polarization. In summary, FE is a promising treatment for SCI, as it is easy to obtain, nonimmunogenic, and effective.


Assuntos
Microglia , Traumatismos da Medula Espinal , Animais , Extratos Celulares , Citocinas/metabolismo , Humanos , Ácido Hialurônico/farmacologia , Hidrogéis , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Traumatismos da Medula Espinal/tratamento farmacológico
6.
Biochem Biophys Res Commun ; 604: 88-95, 2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-35303684

RESUMO

Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-ß-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention.


Assuntos
Senescência Celular , MicroRNAs , RNA Circular , Animais , Proliferação de Células/genética , Senescência Celular/genética , Fibroblastos/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/fisiologia , RNA Circular/genética , RNA Circular/fisiologia
7.
World Neurosurg ; 2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35292408

RESUMO

OBJECTIVE: To explore the sagittal radiological parameters related to clinical recovery of patients with acute traumatic central cord syndrome (ATCCS) and determine the diagnostic value of related variables. METHODS: A retrospective review was performed of 104 patients with ATCCS. Six cervical sagittal balance parameters were collected: Cobb angle, T1 slope, neck tilt, thoracic inlet angle (TIA), C2-C7 sagittal vertex axis, T1 slope - C2-C7 Cobb angle. The patients were assigned to an ideal improvement group and poor improvement group according to their recovery rate. Receiver operating characteristic curve and area under the curve were used to evaluate the significant results of logistic regression and the optimal diagnostic value. RESULTS: Preoperative and postoperative Japanese Orthopaedic Association scores indicated a good recovery after surgical intervention. Radiological findings revealed that neck tilt and TIA were risk factors for poor neurological improvement of patients with ATCCS. Area under the curve (95% confidence interval) values of neck tilt and TIA were 0.763 (0.660-0.866) and 0.749 (0.643-0.855), and cutoff values were 39.1° and 65.6°, respectively. CONCLUSIONS: Lower neck tilt and TIA are risk factors for poor outcomes in patients with ATCCS after surgery. Neck tilt <39° and TIA <66° had significant diagnostic value for poor prognosis.

8.
J Nucl Cardiol ; 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35194752

RESUMO

BACKGROUND: SPECT myocardial perfusion imaging (SPECT MPI) and invasive coronary angiography (ICA) provide complementary clinical information in the diagnosis of coronary artery disease (CAD). We have developed an approach for 3D fusion of perfusion data from SPECT MPI and coronary anatomy from ICA. In this study, we aimed to evaluate its clinical value when compared to the traditional side-by-side readings. METHODS: Thirty-six CAD patients who had at least one stenosis ≥ 50% were retrospectively enrolled. Based on the presence of a perfusion defect in a territory subtended by a coronary vessel, all vessels were classified as matched, unmatched, or normal groups via both the fusion and side-by-side analysis. The treatments recommended by the fusion and side-by-side analysis were compared with those that the patients received. Major adverse cardiac events (MACE), defined as all-cause death, myocardial infarction, unstable angina requiring hospitalization, and unplanned revascularization, were assessed. RESULTS: The overall vessel-based concordance was 78.7% between the fusion and side-by-side analysis. Compared with the side-by-side analysis, 23 coronary arteries (29 equivocal segments) of 19 patients were reclassified via fusion of data. In the matched, unmatched, and normal groups, the numbers of vessels with hemodynamically significant stenosis which caused reversible defect were 37 vs 53, 28 vs 14, and 43 vs 41 (P < .01) when comparing the side-by-side analysis with the fusion, and the revascularization ratios per vessel were 69% vs 88%, 29% vs 10%, and 2% vs 2% between them. During the five-year follow-up, 8 patients (22.2%) experienced MACE. Patients who received the same treatment as the guidance of 3D fusion results (n = 22) had superior outcomes when compared with those who did not (n = 14) (P < .01). CONCLUSIONS: Compared with the side-by-side analysis, the 3D fusion of SPECT MPI and ICA provided incremental diagnostic and prognostic value.

9.
JTO Clin Res Rep ; 3(1): 100257, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34977823

RESUMO

INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

10.
J Surg Oncol ; 125(5): 933-942, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35041203

RESUMO

BACKGROUND AND OBJECTIVES: Lung cancer patients slated for surgery are at high risk of venous thromboembolism (VTE). Precise risk assessment is necessary for providing proper thromboprophylaxis and reducing morbidity and mortality of VTE. METHODS: A multicenter, observational, cross-sectional cohort study, involving patients with primary lung cancer undergoing surgery, was carried out from August 2016 to December 2019. All patients were assessed according to the Caprini risk assessment model (RAM) and a modified scoring system incorporating elevated D-dimer and new stratification of surgical time. The endpoint was confirmed VTE or patient discharge. RESULTS: Out of 1205 patients, 87 (7.2%) were diagnosed with VTE. The area under the curve of modified scores for VTE was 0.759, which was larger than that of the original one (0.589) (p < 0.05). By modified Caprini scoring system, a higher score was associated with increased VTE risk (odds ratio [OR], 1.345; 95% confidence interval [CI], 1.197-1.512; p < 0.001), and there was an increased OR of 4.090 (95% CI, 2.472-6.768, p < 0.001) for VTE in high-risk category patients. CONCLUSION: Modified Caprini RAM showed an improved prediction of high-risk patients with an elevated likelihood of postoperative VTE compared to the original one.


Assuntos
Neoplasias Pulmonares , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Estudos Transversais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
11.
Curr Med Res Opin ; 38(1): 75-81, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34665066

RESUMO

OBJECTIVE: Complications affect the outcome of patients with cirrhosis. The favorable prognosis of patients with Wilson disease (WD)-related cirrhosis suggests that its complications differ from those of hepatitis B virus (HBV) infection-related cirrhosis. We aimed to delineate the differences in complications between WD-related and HBV-related cirrhosis. METHODS: The electronic-medical data from patients with WD-related and HBV-related cirrhosis were extracted and analyzed. RESULTS: In total, 211 patients with WD-related cirrhosis and 374 patients with HBV-related cirrhosis were enrolled. Most patients with WD progressed to cirrhosis <10 years after disease onset, whereas those with HBV infection often progressed after >10 years. Patients with WD-related cirrhosis had a markedly lower prevalence of ascites (8.5% vs. 38.5%), gastroesophageal varices/variceal bleeding (13.3% vs. 47.6%), renal impairment (0 vs. 7.6%) and primary liver cancer (0 vs. 39.3%; all p < .001) than those with HBV-related cirrhosis. After adjustment for potential confounders, patients with WD-related cirrhosis carried a lower risk of varices/variceal bleeding. CONCLUSIONS: Although patients with WD progressed to cirrhosis much faster, the prevalence of complications from WD-related cirrhosis was low. Patients with WD-related cirrhosis were less likely to develop gastroesophageal varices/variceal bleeding than those with HBV-related cirrhosis.


Assuntos
Varizes Esofágicas e Gástricas , Degeneração Hepatolenticular , Varizes Esofágicas e Gástricas/epidemiologia , Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal , Vírus da Hepatite B , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia
12.
Chemosphere ; 286(Pt 3): 131963, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34426263

RESUMO

BACKGROUND: Exposure to air pollution has been linked with altered immune function in adults, but little is known about its effects on early life. This study aimed to investigate the effects of exposure to air pollution during prenatal and postnatal windows on cell-mediated immune function in preschoolers. METHODS: Pre-school aged children (2.9 ± 0.5 y old, n = 391) were recruited from a mother-child cohort study in Wuhan, China. We used a spatial-temporal land use regression (LUR) model to estimate exposures of particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) and ≤10 µm (PM10), and nitrogen dioxide (NO2) during the specific trimesters of pregnancy and the first two postnatal years. We measured peripheral blood T lymphocyte subsets and plasma cytokines as indicators of cellular immune function. We used multiple informant models to examine the associations of prenatal and postnatal exposures to air pollution with cell-mediated immune function. RESULTS: Prenatal exposures to PM2.5, PM10, and NO2 during early pregnancy were negatively associated with %CD3+ and %CD3+CD8+ cells, and during late pregnancy were positively associated with %CD3+ cells. Postnatal exposures to these air pollutants during 1-y or 2-y childhood were positively associated with IL-4, IL-5, IL-6, and TNF-α. We also observed that the associations of prenatal or postnatal air pollution exposures with cellular immune responses varied by child's sex. CONCLUSIONS: Our results suggest that exposure to air pollution during different critical windows of early life may differentially alter cellular immune responses, and these effects appear to be sex-specific.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Imunidade Celular , Masculino , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Gravidez
13.
J Laparoendosc Adv Surg Tech A ; 32(4): 413-421, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34962142

RESUMO

Background: The endoscopic resection of suspected gastric high-grade intraepithelial neoplasia (HGIN) may incidentally cause the patient to suffer from early gastric cancer (EGC), complicating the subsequent clinical management. Identifying the risk factors for such misstaging may help guide the clinical management. Methods: The information obtained from 123,460 patients, who underwent conventional upper gastrointestinal endoscopy at the First Affiliated Hospital of Nanjing Medical University from January 2010 to December 2015, were retrospectively reviewed. Patients with an initial diagnosis of HGIN underwent endoscopic submucosal dissection (ESD), and received a final diagnosis of EGC. The risk factors for the upgraded pathology and noncurative resection were analyzed. Results: Among the 134 patients initially diagnosed with HGIN, 35 (26.12%) patients were finally diagnosed with EGC after ESD. A lesion size of ≥2 cm (odds ratio [OR] = 5.16, 95% confidence interval [CI] = 2.04-13.05; P < .01), ≤4 biopsies taken (OR = 2.73, 95% CI = 1.15-6.48; P < .05), and the presence of upper gastrointestinal bleeding (UGIB; OR = 15.64, 95% CI = 1.29-189.75; P < .05) were the independent risk factors for upgraded pathology. In addition, patients >65 years old (OR = 0.022, 95% CI = 0.901-6.549; P < .05) or with a lesion size of ≥2 cm (OR = 4.237, 95% CI = 1.650-10.878; P < .01) were more likely to endure the noncurative resection. Conclusion: For suspected gastric HGIN patients, age, lesion size, the number of biopsies, and UGIB should be taken into account before deciding on the ESD.


Assuntos
Carcinoma in Situ , Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Idoso , Carcinoma in Situ/etiologia , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Ressecção Endoscópica de Mucosa/efeitos adversos , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Resultado do Tratamento
14.
Aging Cell ; 21(1): e13529, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902213

RESUMO

Circular RNAs (circRNAs) have been established to be involved in numerous processes in the human genome, but their function in vascular aging remains largely unknown. In this study, we aimed to characterize and analyze the function of a circular intronic RNA, ciPVT1, in endothelial cell senescence. We observed significant downregulation of ciPVT1 in senescent endothelial cells. In proliferating endothelial cells, ciPVT1 knockdown induced a premature senescence-like phenotype, inhibited proliferation, and led to an impairment in angiogenesis. An in vivo angiogenic plug assay revealed that ciPVT1 silencing significantly inhibited endothelial tube formation and decreased hemoglobin content. Conversely, overexpression of ciPVT1 in old endothelial cells delayed senescence, promoted proliferation, and increased angiogenic activity. Mechanistic studies revealed that ciPVT1 can sponge miR-24-3p to upregulate the expression of CDK4, resulting in enhanced Rb phosphorylation. Moreover, enforced expression of ciPVT1 reversed the senescence induction effect of miR-24-3p in endothelial cells. In summary, the present study reveals a pivotal role for ciPVT1 in regulating endothelial cell senescence and may have important implications in the search of strategies to counteract the development of age-associated vascular pathologies.


Assuntos
Senescência Celular/genética , Quinase 4 Dependente de Ciclina/genética , Células Endoteliais/metabolismo , MicroRNAs/genética , RNA Circular/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transfecção
16.
Front Med (Lausanne) ; 8: 684238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926480

RESUMO

Cell-free DNA (cfDNA) serves as a footprint of the nucleosome occupancy status of transcription start sites (TSSs), and has been subject to wide development for use in noninvasive health monitoring and disease detection. However, the requirement for high sequencing depth limits its clinical use. Here, we introduce a deep-learning pipeline designed for TSS coverage profiles generated from shallow cfDNA sequencing called the Autoencoder of cfDNA TSS (AECT) coverage profile. AECT outperformed existing single-cell sequencing imputation algorithms in terms of improvements to TSS coverage accuracy and the capture of latent biological features that distinguish sex or tumor status. We built classifiers for the detection of breast and rectal cancer using AECT-imputed shallow sequencing data, and their performance was close to that achieved by high-depth sequencing, suggesting that AECT could provide a broadly applicable noninvasive screening approach with high accuracy and at a moderate cost.

17.
Nat Commun ; 12(1): 6450, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750392

RESUMO

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Receptores ErbB/genética , Gefitinibe/uso terapêutico , Genômica , Humanos , Neoplasias Pulmonares/tratamento farmacológico
18.
Mol Ther Nucleic Acids ; 26: 374-387, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34552819

RESUMO

Endothelial cell senescence is one of the most important causes of vascular dysfunction and atherosclerosis. Circular RNAs (circRNAs) are endogenous RNA molecules with covalently closed-loop structures, which have been reported to be abnormally expressed in many human diseases. However, the potential role of circRNAs in endothelial cell senescence and atherosclerosis remains largely unknown. Here, we compared the expression patterns of circRNAs in young and senescent human endothelial cells with RNA sequencing. Among the differentially expressed circRNAs, circGNAQ, a circRNA enriched in vascular endothelium, was significantly downregulated in senescent endothelial cells. circGNAQ silencing triggered endothelial cell senescence, as determined by a rise in senescence-associated ß-galactosidase activity, reduced cell proliferation, and suppressed angiogenesis; circGNAQ overexpression showed the opposite effects. Mechanistic studies revealed that circGNAQ acted as an endogenous miR-146a-5p sponge to increase the expression of its target gene PLK2 by decoying the miR-146a-5p, thereby delaying endothelial cell senescence. In vivo studies showed that circGNAQ overexpression in the endothelium inhibited endothelial cell senescence and atherosclerosis progression. These results suggest that circGNAQ plays critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that the management of circGNAQ provides a potential therapeutic approach for limiting the progression of atherosclerosis.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34379598

RESUMO

The article investigates full information control problem for switched neural networks subject to fault and disturbance. First, the main objective is realizing interval stability and zero tracking error under condition that neither of the neuron states' vectors including the plant and reference models is available. Second, the desired full information controller and neural networks' observer are designed to ensure observer-based dynamic error system mean-square exponentially stable with sufficient condition of strict weight performance levels. Finally, we concentrate on stability analyses and fault tolerance for switched neural networks with fault accompanied by disturbance through linear matrix inequalities (LMIs), Lyapunov function, and average dwell time, discussing it according to different values of fault. Finally, simulation examples are listed to account for the availability and effectiveness of the research methodology.

20.
IEEE Trans Cybern ; PP2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464283

RESUMO

This article investigates the optimal control strategy problem for nonzero-sum games of the immune system based on adaptive dynamic programming (ADP). First, the main objective is approximating a Nash equilibrium between the tumor cells and the immune cell population, which is governed through chemotherapy drugs and immunoagents guided by the mathematical growth model of the tumor cells. Second, a novel intelligent nonzero-sum games-based ADP is put forward to solve the optimization control problem by reducing the growth rate of tumor cells and minimizing chemotherapy drugs and immunotherapy drugs. Meanwhile, the convergence analysis and iterative ADP algorithm are specified to prove feasibility. Finally, simulation examples are listed to account for availability and effectiveness of the research methodology.

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