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1.
Neural Regen Res ; 17(2): 433-439, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34269220

RESUMO

MicroRNAs (miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. MicroRNA-29b (miR-29b) plays a broad and critical role in brain homeostasis. In this study, we tested the function of miR-29b in animal and cell models by inhibiting miR-29b expression. Mouse models of middle cerebral artery occlusion were established using the modified Zea-Longa suture method. Prior to modeling, 50 nmol/kg miR-29b antagomir was injected via the tail vein. MiR-29b expression was found to be abnormally increased in ischemic brain tissue. The inhibition of miR-29b expression decreased the neurological function score and reduced the cerebral infarction volume and cell apoptosis. In addition, the inhibition of miR-29b significantly decreased the malondialdehyde level, increased superoxide dismutase activity, and Bcl-2 expression, and inhibited Bax and Caspase3 expression. PC12 cells were treated with glutamate for 12 hours to establish in vitro cell models of ischemic stroke and then treated with the miR-29 antagomir for 48 hours. The results revealed that miR-29b inhibition in PC12 cells increased Bcl-2 expression and inhibited cell apoptosis and oxidative damage. These findings suggest that the inhibition of miR-29b inhibits oxidative stress and cell apoptosis in ischemic stroke, producing therapeutic effects in ischemic stroke. This study was approved by the Laboratory Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University (approval No. 201709276S) on September 27, 2017.

2.
Analyst ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783798

RESUMO

In this study, a novel method that combines electrochemiluminescence (ECL) analysis and digital image processing was developed for the detection of sulfonamides. This method is based on the ECL system of ruthenium terpyridine, with 1 mM tripropylamine as a co-reactant to enhance the performance. Under the optimal conditions comprising a solution of pH 7 and a scanning rate of 0.08 V s-1, the Pt electrode has an excellent linear detection range from 5 µM to 5 mM, with a detection limit of 0.85 µM (S/N = 3). A wireless camera is used to record the light-emitting process. The recordings are processed, and the digital images are extracted using image-processing algorithms implemented in Python to calculate the brightness value of the image, which has a linear relationship with the logarithm of the sulfonamide concentration. Image analysis simplifies and improves the stability of the ECL analysis process, while also increasing the speed of analysis. The results indicate that the method can successfully detect a sulfonamide concentration of 5 µM. Thus, the analysis method of ECL combined with image processing is feasible for the detection of sulfonamides, thereby displaying its potential applicability as a novel method in drug and food safety, for instance, for sulfonamide detection in antibiotics.

3.
Biomed Res Int ; 2021: 3995789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671673

RESUMO

Objective: To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL. Materials and Methods: In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance. Results: PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001). Conclusions: For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.

4.
Materials (Basel) ; 14(20)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34683635

RESUMO

During the process of electroslag remelting (ESR) of steel containing titanium and aluminum, the activity ratio between titania and alumina in CaF2-CaO-MgO-Al2O3-TiO2 slag must be fixed in order to guarantee the titanium and aluminum contents in the ESR ingots. Under the condition of fixed activity ratio between titania and alumina in the slag, the melting temperature of slag should be investigated to improve the surface quality of ESR ingots. Therefore, this paper focuses on finding a kind of slag with low melting temperature that can be used for producing steel containing titanium. In the current study, the thermodynamic equilibrium of 3[Ti] + 2(Al2O3) = 4[Al] + 3(TiO2) between SUS321 steel and the two slag systems (CaF2:MgO:CaO:Al2O3:TiO2 = 46:4:25:(25 - x):x and CaF2:MgO:CaO:Al2O3:TiO2 = 46:4:(25 - 0.5 x):(25 - 0.5 x):x) are studied in an electrical resistance furnace based on Factsage software. After obtaining the equilibrium slag with fixed activity ratio between titania and alumina, the melting temperatures of the two slag systems are studied using slag melting experimental measurements and phase diagrams. The results show that the slag systems CaF2:MgO:CaO:Al2O3:TiO2 = 46:4:25:(25 - x):x, which consists of pre-melted slag S0 (CaF2:MgO:CaO:Al2O3 = 46:4:25:25) and pre-melted slag F1 (CaF2:MgO:CaO:TiO2 = 46:4:25:25), can not only control the aluminum and titanium contents in steel, but also have the desired low melting temperature property.

5.
Polymers (Basel) ; 13(20)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34685354

RESUMO

One of the major challenges for lung cancer gene therapy is to find a gene delivery vector with high efficiency and low toxicity. In this study, low-molecular-weight polyethyleneimine (PEI, 1.8 kDa) was grafted onto the side chains of Bombyx mori silk fibroin (BSF) to prepare cationized BSF (CBSF), which was used to package the plasmid DNA (pDNA) encoded by the inhibitor of growth 4 (ING4) and interleukin-24 (IL-24). FTIR and 1H-NMR spectra demonstrated that PEI was effectively coupled to the side chains of BSF by amino bonds. The results of the trinitrobenzene sulfonic acid method and zeta potential showed that the free amino group content on BSF increased from 125.1 ± 1.2 µmol/mL to 153.5 ± 2.2 µmol/mL, the isoelectric point increased from 3.68 to 8.82, and the zeta potential reversed from - 11.8 ± 0.1 mV to + 12.4 ± 0.3 mV after PEI grafting. Positively charged CBSF could package pDNA to form spherical CBSF/pDNA complexes. In vitro, human lung adenocarcinoma A549 cells and human embryonic lung fibroblast WI-38 cells were transfected with CBSF/pDNA complexes. Confocal laser scanning microscopy analysis and flow cytometry tests showed that CBSF/pDNA complexes can effectively transfect A549 cells, and the transfection efficiency was higher than that of 25 kDa PEI/pDNA complexes. CCK-8 assay results showed that CBSF/pDNA complexes significantly inhibited the proliferation of A549 cells but had no significant effect on WI-38 cells and exhibited lower cytotoxicity to WI-38 cells than 25 kDa PEI. Therefore, a gene delivery system, constructed with the low-molecular-weight PEI-modified silk fibroin protein and the ING4-IL-24 double gene coexpression plasmid has potential applications in gene therapy for lung cancer.

6.
Arch Anim Breed ; 64(2): 375-386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34584939

RESUMO

Litter size is an important component trait of doe reproduction. By improving it, production efficiency and economic benefits can be significantly provided. Genetic marker-assisted selection (MAS) based on proven molecular indicators could enhance the efficacy of goat selection, as well as litter size trait. Many molecular markers have been identified that they can be used to improve litter size in different goat breeds. However, the presence and value of these markers vary among goat breeds. In the present study, we used the reported loci on other breeds of goat as candidate loci to detect whether these loci appear in this Nubian goat population; then we proceed to genotype and detect surrounding loci (50 bp) by multiplex PCR and sequencing technology. As a result, 69 mutations (59 SNPs and 10 indels) were screened out from 23 candidate genes in Nubian goat population, 12 loci were significantly associated with the litter size of first-parity individuals; 5 loci were significantly associated with the litter size of second-parity individuals; 3 loci were significantly associated with the litter size of third-parity individuals. In addition, five loci were significantly associated with the average litter size. The additive effect value of KITLG: g.18047318 G > A in first parity, KITLG: g.18152042G > A in third parity, KISS-1: g.1341674 C > G in first parity, and GHR: g.32134187G > A in second parity exceed more than 0.40, and the preponderant alleles are G, C, A and G, respectively. Further, linkage disequilibrium analysis of 21 mutation loci shows that 3 haplotype blocks are formed, and the litter size of combination type AACC in KISS-1 gene and AAGG in KITLG gene are significantly lower than that of other combinations genotype in first parity ( P < 0.05 ). These findings can provide effective candidate DNA markers for selecting superior individuals in Nubian goat breeding.

7.
World J Gastroenterol ; 27(31): 5232-5246, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34497447

RESUMO

BACKGROUND: Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice. AIM: To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies. METHODS: With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital. RESULTS: The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time (P = 0.32; P = 0.16, respectively). CONCLUSION: CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted.


Assuntos
Pólipos do Colo , Aprendizado Profundo , Inteligência Artificial , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Computadores , Humanos
8.
Entropy (Basel) ; 23(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34356460

RESUMO

Cross-modality person re-identification is the study of images of people matching under different modalities (RGB modality, IR modality). Given one RGB image of a pedestrian collected under visible light in the daytime, cross-modality person re-identification aims to determine whether the same pedestrian appears in infrared images (IR images) collected by infrared cameras at night, and vice versa. Cross-modality person re-identification can solve the task of pedestrian recognition in low light or at night. This paper aims to improve the degree of similarity for the same pedestrian in two modalities by improving the feature expression ability of the network and designing appropriate loss functions. To implement our approach, we introduce a deep neural network structure combining heterogeneous center loss (HC loss) and a non-local mechanism. On the one hand, this can heighten the performance of feature representation of the feature learning module, and, on the other hand, it can improve the similarity of cross-modality within the class. Experimental data show that the network achieves excellent performance on SYSU-MM01 datasets.

9.
Analyst ; 146(18): 5610-5618, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34378564

RESUMO

The rapid development of industrial technologies continuously increases the heavy metal pollution of water resources. Recently, portable electrochemical analysis-based devices for detecting heavy metal ions have attracted much attention due to their excellent performance and low fabrication costs. However, it has proven difficult to accommodate complex testing needs in a cost-effective manner. To address these limitations, we propose a new system for the in situ detection of heavy metals in wastewater using an organic light-emitting diode-based panel to display data in real time and Bluetooth to transmit data to a smartphone for rapid analysis. The fabricated device integrates an in situ signal analysis circuit, a Bluetooth chip, a photocured 3D-printed shell, and an electrode sleeve interface. In addition, a fully screen-printed functional electrode plate containing chitosan/PANi-Bi nanoparticle@graphene oxide multi-walled carbon nanotubes is utilized for the rapid detection of heavy metal ions. This device can perform wireless data transmission and analysis and in situ signal acquisition and processing. The sensor exhibits a high sensitivity (Hg2+: 88.34 µA ppm-1 cm-2; Cu2+: 0.956 µA ppm-1 cm-2), low limit of detection (Hg2+: 10 ppb, Cu2+: 0.998 ppm) and high selectivity during the detection of copper and mercury ions in tap water under non-laboratory conditions, and the results of real-time tests reveal that parameters measured in the field and laboratory environments are identical. Hence, this small, portable, electrochemical sensor with a screen-printed electrode can be effectively used for the real-time detection of copper and mercury ions in complex water environments.


Assuntos
Metais Pesados , Nanotubos de Carbono , Eletrodos , Íons , Esgotos
10.
World J Clin Cases ; 9(22): 6287-6299, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34434995

RESUMO

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix-associated protein. Studies have revealed that SPARC is involved in the cell interaction and function including proliferation, differentiation, and apoptosis. However, the role of SPARC in cancer is controversial, as it was reported as the promoter or suppressor in different cancers. Further, the role of SPARC in lymphoma is unclear. AIM: To identify the expression and significance of SPARC in lymphoma, especially in diffuse large B-cell lymphoma (DLBCL). METHODS: The expression analysis of SPARC in different cancers was evaluated with Oncomine. The Brune, Eckerle, Piccaluga, Basso, Compagno, Alizadeh, and Rosenwald datasets were included to evaluate the mRNA expression of SPARC in lymphoma. The Cancer Genome Atlas (TCGA)-DLBCL was used to analyze the diagnostic value of SPARC in DLBCL. The Compagno and Brune DLBCL datasets were used for validation. Then, the diagnostic value was evaluated with the receiver operating characteristic (ROC) curve. The Kaplan-Meier plot was conducted with TCGA-DLBCL, and the ROC analysis was performed based on the survival time. Further, the overall survival analysis based on the level of SPARC expression was performed with the GSE4475 and E-TABM-346. The Gene Set Enrichment Analyses (GSEA) was performed to make the underlying mechanism-regulatory networks. RESULTS: The pan-cancer analysis of SPARC showed that SPARC was highly expressed in the brain and central nervous system, breast, colon, esophagus, stomach, head and neck, pancreas, and sarcoma, especially in lymphoma. The overexpression of SPARC in lymphoma, especially DLBCL, was confirmed in several datasets. The ROC analysis revealed that SPARC was a valuable diagnostic biomarker. More importantly, compared with DLBCL patients with low SPARC expression, those with higher SPARC expression represented a higher overall survival rate. The ROC analysis showed that SPARC was a favorable prognostic biomarker for DLBCL. Results of the GSEA confirmed that the high expression of SPARC was closely associated with focal adhesion, extracellular matrix receptor interaction, and leukocyte transendothelial migration, which suggested that SPARC may be involved in the regulation of epithelial-mesenchymal transition, KRAS, and myogenesis in DLBCL. CONCLUSION: SPARC was highly expressed in DLBCL, and the overexpression of SPARC showed sound diagnostic value. More interestingly, the overexpression of SPARC might be a favorable prognostic biomarker for DLBCL, suggesting that SPARC might be an inducible factor in the development of DLBCL, and inducible SPARC was negative in some oncogenic pathways. All the evidence suggested that inducible SPARC might be a good diagnostic and prognostic biomarker for DLBCL.

11.
Transl Androl Urol ; 10(6): 2435-2446, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34295730

RESUMO

Background: This study attempted to develop a nomogram for predicting clinically significant prostate cancer (cs-PCa) in the transition zone (TZ) with the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) score based on biparametric magnetic resonance imaging (bp-MRI) and clinical indicators. Methods: We retrospectively reviewed 383 patients with suspicious prostate lesions in the TZ as a training cohort and 128 patients as the validation cohort from January 2015 to March 2020. Multivariable logistic regression analysis was performed to determine independent predictors for building a nomogram, and the performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC), the calibration curve and decision curve. Results: The PI-RADS v2.1 score and prostate-specific antigen density (PSAD) were independent predictors of TZ cs-PCa. The prediction model had a significantly higher AUC (0.936) than the individual predictors (0.914 for PI-RADS v2.1 score, P=0.045, 0.842 for PSAD, P<0.001). The nomogram showed good discrimination (AUC of 0.936 in the training cohort and 0.963 in the validation cohort) and favorable calibration. When the PI-RADS v2.1 score was combined with PSAD, the diagnostic sensitivity and specificity were 80.7% and 93.8%, respectively, which were better than those of the PI-RADS v2.1 score (sensitivity, 74.2%; specificity, 92.5%) and PSAD (sensitivity, 66.1%; specificity, 88.2%). Conclusions: The newly constructed nomogram exhibits satisfactory predictive accuracy and consistency for TZ cs-PCa. PI-RADS v2.1 based on bp-MRI is a strong predictor in the detection of TZ cs-PCa. Adding PSAD to PI-RADS v2.1 could improve its diagnostic performance, thereby avoiding unnecessary biopsies.

12.
Cancer Chemother Pharmacol ; 88(5): 825-836, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34324028

RESUMO

PURPOSE: The purpose of this study is to characterize niraparib pharmacokinetics (PK) and safety in patients with normal hepatic function (NHF) versus moderate hepatic impairment (MHI). METHODS: Patients with advanced solid tumors were stratified by NHF or MHI (National Cancer Institute-Organ Dysfunction Working Group criteria [bilirubin > 1.5-3 × upper limit of normal and any aspartate aminotransferase elevation]). In the PK phase, all patients received one 300 mg dose of niraparib. In the extension phase, patients with MHI received niraparib 200 mg daily; patients with NHF received 200 or 300 mg based on weight (< 77 kg, ≥ 77 kg)/platelets (< 150,000/µL, ≥ 150,000/µL). PK parameters included maximum concentration (Cmax), area under the curve to last measured concentration (AUClast) and extrapolated to infinity (AUCinf). Safety was assessed in both phases. Exposure-response (E-R) modeling was used to predict MHI effects on exposure and safety of niraparib doses ≤ 200 mg or 300/200 mg or 200/100 mg weight/platelet regimens. RESULTS: In the PK phase (NHF, n = 9; MHI, n = 8), mean niraparib Cmax was 7% lower in patients with MHI versus NHF. Mean exposure (AUClast, AUCinf) was increased by 45% and 56%, respectively, in patients with MHI without impacting tolerability. In the extension phase (NHF, n = 8; MHI, n = 7), the overall safety profile was consistent with previous trials. In patients with MHI, E-R modeling predicted niraparib 200 mg reduced Grade ≥ 3 thrombocytopenia incidence, whereas a 200/100 mg regimen yielded exposures below efficacy-associated levels in 15% of patients. CONCLUSION: These findings support adjusting the 300 mg niraparib starting dose to 200 mg QD in patients with MHI. TRIAL REGISTRATION: NCT03359850; registered December 2, 2017.

13.
Nano Lett ; 21(16): 7070-7078, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34100613

RESUMO

Using a three-dimensional (3D) Li-ion conducting ceramic network, such as Li7La3Zr2O12 (LLZO) garnet-type oxide conductor, has proved to be a promising strategy to form continuous Li ion transfer paths in a polymer-based composite. However, the 3D network produced by brittle ceramic conductor nanofibers fails to provide sufficient mechanical adaptability. In this manuscript, we reported a new 3D ion-conducting network, which is synthesized from highly loaded LLZO nanoparticles reinforced conducting polymer nanofibers, by creating a lightweight continuous and interconnected LLZO-enhanced 3D network to outperform conducting heavy and brittle ceramic nanofibers to offer a new design principle of composite electrolyte membrane featuring all-round properties in mechanical robustness, structural flexibility, high ionic conductivity, lightweight, and high surface area. This composite-nanofiber design overcomes the issues of using ceramic-only nanoparticles, nanowires, or nanofibers in polymer composite electrolyte, and our work can be considered as a new generation of composite electrolyte membrane in composite electrolyte development.

14.
Small ; 17(31): e2100383, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34171160

RESUMO

The rectification of ion transport through biological ion channels has attracted much attention and inspired the thriving invention and applications of ionic diodes. However, the development of high-performance ionic diodes is still challenging, and the working mechanisms of ionic diodes constructed by 1D ionic nanochannels have not been fully understood. This work reports the systematic investigation of the design and mechanism of a new type of ionic diode constructed from horizontally aligned multi-walled carbon nanotubes (MWCNTs) with oppositely charged polyelectrolytes decorated at their two entrances. The major design and working parameters of the MWCNT-based ionic diode, including the ion channel size, the driven voltage, the properties of working fluids, and the quantity and length of charge modification, are extensively investigated through numerical simulations and/or experiments. An optimized ionic current rectification (ICR) ratio of 1481.5 is experimentally achieved on the MWCNT-based ionic diode. These results promise potential applications of the MWCNT-based ionic diode in biosensing and biocomputing. As a proof-of-concept, DNA detection and HIV-1 diagnosis is demonstrated on the ionic diode. This work provides a comprehensive understanding of the working principle of the MWCNT-based ionic diodes and will allow rational device design and optimization.


Assuntos
Nanotubos de Carbono , DNA , Transporte de Íons , Íons , Polieletrólitos
15.
Sci Rep ; 11(1): 9938, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976305

RESUMO

The aim of this paper was to identify DNA methylation based biomarkers for predicting overall survival (OS) of stage I-II lung adenocarcinoma (LUAD) patients. Methylation profile data of patients with stage I-II LUAD from The Cancer Genome Atlas (TCGA) database was used to determine methylation sites-based hallmark for stage I-II LUAD patients' OS. The patients were separated into training and validation datasets by using median risk score as cutoff. Univariate Cox, least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were employed to develop a DNA methylation signature for OS of patients with stage I-II LUAD. As a result, an 11-DNA methylation signature was determined to be critically associated with the OS of patients with stage I-II LUAD. Analysis of receiver operating characteristics (ROC) suggested a high prognostic effectiveness of the 11-DNA methylation signature in patients with stage I-II LUAD (AUC at 1, 3, 5 years in training set were (0.849, 0.879, 0.831, respectively), validation set (0.742, 0.807, 0.904, respectively), entire TCGA dataset (0.747, 0.818, 0.870, respectively). Kaplan-Meier survival analyses exhibited that survival was significantly longer in the low-risk cohort compared to the high-risk cohort in the training dataset (P = 7e - 07), in the validation dataset (P = 1e - 08), and in the all-cohort dataset (P = 6e - 14). In addition, a nomogram was developed based on molecular factor (methylation risk score) as well as clinical factors (age and cancer status) (AUC at 1, 3, 5 years entire TCGA dataset were 0.770, 0.849, 0.979, respectively). The result verified that our methylomics-associated nomogram had a strong robustness for predicting stage I-II LUAD patients' OS. Furthermore, the nomogram combined clinical and molecular factors to determine an individualized probability of recurrence for patients with stage I-II LUAD, which stood for a major advance in the field of personalized medicine for pulmonary oncology. Collectively, we successfully identified a DNA methylation biomarker and a DNA methylation-based nomogram to predict the OS of patients with stage I-II LUAD.


Assuntos
Adenocarcinoma de Pulmão/mortalidade , Biologia Computacional/métodos , Epigenoma/genética , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Estudos de Coortes , DNA/genética , Metilação de DNA/genética , Metilação de DNA/fisiologia , Bases de Dados Genéticas , Intervalo Livre de Doença , Epigenoma/fisiologia , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/genética , Estadiamento de Neoplasias/métodos , Nomogramas , Prognóstico , Curva ROC , Fatores de Risco , Transcriptoma/genética
16.
Nanomedicine (Lond) ; 16(10): 839-853, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33890489

RESUMO

Aim: To obtain a gene carrier that can effectively deliver loaded therapeutic genes to tumor cells, avoid toxic effects on normal cells and reduce nonspecific adsorption of plasma proteins. Methods: The conjugate of poly(ethylene glycol) (PEG) and MMP2SSP (PEG-MMP2SSP) was covalently coupled to cationized Antheraea pernyi silk fibroin (CASF) through disulfide bond exchange reaction to obtain a PEG-MMP2SSP-modified CASF (CASFMP). Results: The PEG chains were effectively cleaved from the CASFMP by MMP2. CASFMP/pDNA complexes inhibited human fibrosarcoma cell proliferation, and its cytotoxicity to human normal embryonic kidney cells was significantly lower than that of poly(ethylenimine)/pDNA after coculturing with cells for 24 h. Conclusion: CASFMP is a promising compound for use in gene therapy.


Assuntos
Fibroínas , Mariposas , Animais , Técnicas de Transferência de Genes , Terapia Genética , Humanos , Polietilenoglicóis , Seda
17.
Aging (Albany NY) ; 13(8): 11281-11295, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33820867

RESUMO

BACKGROUND: Developmental dysplasia of the hip (DDH) is the most common joint disease in child orthopedics. Secreted Frizzled-Related Protein 3 (FRZB) plays an important role in joint development. however, no direct association between FRZB and DDH has been demonstrated. METHODS: Analysis of genotype distribution and allele frequency for detected single nucleotide polymorphisms (SNP) of FRZB was performed. FRZB expression was assayed in DDH joint tissues. Further experiments to identify the chondrogenic properties of FRZB were conducted. Potential upstream miRNAs for FRZB were assayed in DDH. RESULTS: Significant difference in genotype distribution for rs3768842 (OR=1.46, P=0.0081) and rs2242040 (OR=0.65, P=0.0067) was found. DDH joint tissues showed significantly higher FRZB expression. FRZB demonstrated chondrogenic and anti-hypertrophic properties in vitro. FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. Upstream miRNAs regulating FRZB expression were identified in DDH synovial fluid. Experiments indicated that downregulated miRNA-454 caused FRZB upregulation in DDH joint. CONCLUSION: Dysregulated FRZB and its loci were associated with DDH. As a Wnt antagonist with chondrogenic properties, FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. FRZB in multiple DDH joint tissues might be mediated by the dysregulated miRNA expression profiles in the joint synovial fluid.


Assuntos
Condrogênese/genética , Displasia do Desenvolvimento do Quadril/genética , Articulação do Quadril/patologia , MicroRNAs/metabolismo , Proteínas/genética , Animais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Criança , Displasia do Desenvolvimento do Quadril/patologia , Displasia do Desenvolvimento do Quadril/cirurgia , Regulação da Expressão Gênica no Desenvolvimento , Frequência do Gene , Técnicas de Silenciamento de Genes , Loci Gênicos , Predisposição Genética para Doença , Articulação do Quadril/crescimento & desenvolvimento , Articulação do Quadril/cirurgia , Humanos , Camundongos , Polimorfismo de Nucleotídeo Único , Cultura Primária de Células , Proteínas/metabolismo , Líquido Sinovial/metabolismo
18.
Cell Stress Chaperones ; 26(3): 563-574, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33743152

RESUMO

Heat stress (HS) results in health problems in animals. This study was conducted to investigate the effect and the underlying mechanism of HS on the proliferation and differentiation process of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated at 37 °C or 41.5 °C. HS up-regulated the mRNA and protein expression level of heat shock protein 70 (HSP70). Furthermore, the proliferation of 3T3-L1 preadipocytes were significantly inhibited after HS treatment for 2 days. A large number of accumulated lipid droplets were observed under the microscope after HS treatment for 8 days. Notably, the result of oil red O staining showed that the number of lipid droplets increased significantly and the differentiation ability of the cells was enhanced after HS. Moreover, after 2 and 8 d of differentiation, HS increased the transcription levels of fat synthesis genes including peroxisome proliferators activated receptor γ (PPARγ), fatty acid binding protein 2 (AP2), fatty acid synthase (FAS) and CCAAT enhancer binding protein α (CEBPα) genes, while decreasing the transcription levels of lipid decomposition genes including ATGL and HSL genes. In addition, HS reduced the expression of AMPK and PGC-1α, as well as the dephosphorylation of AMPK. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) can eliminate HS induced lipogenesis by activating AMPK. These results indicated that HS inhibited the proliferation of 3T3-L1 preadipocytes and promoted lipid accumulation by inhibiting the AMPK-PGC-1α signaling pathway in 3T3-L1 preadipocytes. This work lays a theoretical foundation for improving the effect of HS on meat quality of livestock and provides a new direction for the prevention of obesity caused by HS.

19.
Phys Chem Chem Phys ; 23(13): 7615-7636, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33404037

RESUMO

Grazing incidence fast atom diffraction (GIFAD) at surfaces has made rapid progress and has established itself as a surface analysis tool where effective energy E⊥ of the motion towards the surface is in the same range as that in thermal energy atom scattering (TEAS). To better compare the properties of both techniques, we use the diffraction patterns of helium and neon atoms impinging on a LiF (001) surface as a model system. E-Scan, θ-scan, and φ-scan are presented where the primary beam energy E is varied between a few hundred eV up to five keV, the angle of incidence θi between 0.2 and 2° and the azimuthal angle φi around 360°. The resulting diffraction charts are analyzed in terms of high and low values of effective energy E⊥. The former provides high resolution at the positions of the surface atoms and the attached repulsive interaction potentials while the second is sensitive to the attractive forces towards the surface. The recent progress of inelastic diffraction is briefly presented.

20.
AJR Am J Roentgenol ; 216(5): 1247-1256, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32755220

RESUMO

BACKGROUND. PI-RADS version 2.1 (v2.1) introduced a number of key changes to the assessment of transition zone (TZ) lesions. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement and diagnostic accuracy for detecting TZ prostate cancer (PCa) and clinically significant PCa (csPCa) by use of PI-RADS v2 and PI-RADS v2.1 among radiologists with different levels of experience. METHODS. This retrospective study included 355 biopsy-naïve patients who from January 2017 to March 2020 underwent prostate MRI that showed a TZ lesion and underwent subsequent biopsy. PCa was diagnosed in 93 patients (International Society of Urological Pathology [ISUP] grade group 1, n = 34; ISUP grade group ≥ 2, n = 59) and non-cancerous lesions in 262 patients. Five radiologists with varying experience in prostate MRI scored lesions using PI-RADS v2 and PI-RADS v2.1 in sessions separated by at least 4 weeks. Interobserver agreement was evaluated with kappa and Kendall W statistics. ROC curve analysis was used to evaluate performance in detection of TZ PCa and csPCa. RESULTS. Interobserver agreement among all readers was higher for PI-RADS v2.1 than for PI-RADS v2 (mean weighted κ = 0.700 vs 0.622; Kendall W = 0.805 vs 0.728; p = .03). The pooled AUC values for detecting TZ PCa and csPCa were higher among all readers using PI-RADS v2.1 (0.866 vs 0.827 for TZ PCa; 0.929 vs 0.899 for TZ csPCa; p < .001). For detecting TZ PCa, the pooled sensitivity, specificity, and accuracy were 86.9%, 79.4%, and 75.4% among all readers for PI-RADS v2.1 compared with 79.4%, 71.8%, and 73.8% for PI-RADS v2. For detecting TZ csPCa, the pooled sensitivity, specificity, and accuracy were 84.8%, 90.9%, and 89.9% among all readers for PI-RADS v2.1 compared with 81.4%, 89.9%, and 88.5% for PI-RADS v2. Reader 1, who had the least experience, had the lowest sensitivity, specificity, and accuracy (78.0%, 89.2%, and 87.3%). Reader 5, who had the most experience, had the highest sensitivity, specificity, and accuracy (88.1%, 92.9%, and 92.1%) in detecting csPCa. CONCLUSION. PI-RADS v2.1 had better interobserver agreement and diagnostic accuracy than PI-RADS v2 for evaluating TZ lesions. Reader experience continues to affect the performance of prostate MRI interpretation with PI-RADS v2.1. CLINICAL IMPACT. PI-RADS v2.1 is more accurate and reproducible than PI-RADS v2 for the diagnosis of TZ PCa.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Sistemas de Informação em Radiologia/normas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
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