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1.
Small ; 20(1): e2304720, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37649208

RESUMEN

The development of nanomaterials with high photothermal conversion efficiency has been a hot issue. In this work, a novel photothermal nanomaterial is synthesized using Prussian blue nanocubes (PBNCs) as the photothermal active substance and covalent organic framework (COF) as the substrate. The as-prepared COF@PBNCs show a high photothermal conversion efficiency of 59.1%, significantly higher than that of pure PBNCs (32.5%). A new circuit path is generated with the combination of COF, which prevents the direct combination of thermal electrons and holes, as well as enhances the nonradiation transition of PBNCs. Besides, the imine groups on COF as the coordination and reduction agent allow the in situ growth of PBNCs, and the dense micropores of COF as the ideal heat conduction channels can also be the potential factors for the enhanced photothermal property. The photothermal property of COF@PBNCs is further used in the construction of immunosensor for the detection of furosemide (FUR). With the help of handheld thermal imager, the concentration of FUR can be easily read, thus shedding a new light in the construction of visual sensor for simple and low-cost point-of-care testing.

2.
Int J Immunogenet ; 51(1): 10-19, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37962280

RESUMEN

C-C chemokine receptor 5 (CCR5) plays a crucial role in the regulation of immune cell activation and migration as well as the progression of many cancers. We performed an in silico analysis using public data resources and found that the lung cancer patients with higher CCR5 expression had a notably better overall survival than those with lower CCR5 expression patients and CCR5 expression level is positive correlated with the infiltration of immune cells, such as B, CD8+ T and CD4+ T cells, in both lung adenocarcinoma and lung squamous cell cancer. In the present study, we investigated the association between the promoter polymorphism of CCR5 and nonsmall cell lung cancer (NSCLC). A case-control study of 449 NSCLC patients and 516 controls of Chinese Han population was conducted, along with polymorphism detection using a sequencing method. A dual-luciferase reporter assay system was used to analyse the transcriptional activity of CCR5 promoter variations. Our results showed that the frequency of rs1799987-AA was significantly higher in the NSCLC group than in the controls in recessive model (p = .007, OR = 1.66 95% confidence interval [CI]: 1.14-2.40, adjusted by sex and age); the G allele showed a significant associated with NSCLC in dominant model (p = .003, OR = 1.64, 95%CI: 1.18-2.28, adjusted by sex and age). Compared with haplotype H1 rs2227010-rs2734648-rs1799987-rs1799988-rs1800023-rs1800024: A-T-G-T-G-C, haplotype H5: A-G-G-T-G-C increased the risk of NSCLC by over 10-fold (p < .0001, OR = 16.09, 95%CI: 5.37-48.20, adjusted by sex and age) and notably depressed the transcriptional activity of the CCR5 promoter in 293T, A549, H1299 and HeLa cells. In conclusion, CCR5 promoter polymorphisms are significantly associated with NSCLC by affecting the transcriptional activity of the CCR5 promoter.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Frecuencia de los Genes , Estudios de Casos y Controles , Células HeLa , Polimorfismo de Nucleótido Simple , Neoplasias Pulmonares/genética , Receptores CCR5/genética , Predisposición Genética a la Enfermedad
3.
Biomed Chromatogr ; 38(8): e5929, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38881323

RESUMEN

The Runchang-Tongbian (RCTB) formula is a traditional Chinese medicine (TCM) formula consisting of four herbs, namely Cannabis Fructus (Huomaren), Rehmanniae Radix (Dihuang), Atractylodis Macrocephalae Rhizoma (Baizhu), and Aurantii Fructus (Zhiqiao). It is widely used clinically because of its beneficial effect on constipation. However, its strong bitter taste leads to poor patient compliance. The bitter components of TCM compounds are complex and numerous, and inhibiting the bitter taste of TCM has become a major clinical challenge. Here, we use ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) and high-resolution mass spectrometry to identify 59 chemical components in the TCM compound RCTB formula. Next, four bitter taste receptors, TAS2R39, TAS2R14, TAS2R7, and TAS2R5, which are tightly bound to the compounds in RCTB, were screened as molecular docking receptors using the BitterX database. The top-three-scoring receptor-small-molecule complexes for each of the four receptors were selected for molecular dynamics simulation. Finally, seven bitter components were identified, namely six flavonoids (rhoifolin, naringin, poncirin, diosmin, didymin, and narirutin) and one phenylpropanoid (purpureaside C). Thus, we proposed a new method for identifying the bitter components in TCM compounds, which provides a theoretical reference for bitter taste inhibition in TCM compounds.


Asunto(s)
Medicamentos Herbarios Chinos , Espectrometría de Masas , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Espectrometría de Masas/métodos , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Humanos , Gusto , Cromatografía Líquida con Espectrometría de Masas
4.
Anal Chem ; 95(30): 11383-11390, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37458998

RESUMEN

Point-of-care testing (POCT), with its portability and high sensitivity, is an analytical device for rapid on-site sensing and detection. In this study, a POCT device was designed for the portable detection of illegal additives by integrating a coil device that can visually sense color distance and a two-electrode electrochemical system. Real-time monitoring of pressure changes was achieved by driving CeO2@Pt/Au nanoparticle (NP)-labeled antibodies into a competitive immunoreaction, in which CeO2 and Pt/Au synergistically catalyzed the production of large amounts of O2 from H2O2, leading to a significant increase in gas within the closed chamber. Attractively, the coil device converted the pressure stimulus into visually readable change in distance for semi-quantitative detection of the target substance, while the electrical signal output caused by the changes of the solution around the electrodes achieved accurate and reliable quantification of the target. In addition, the proposed dual-mode pressure immunoassay device has acceptable selectivity, stability, and reproducibility. Herein, this portable device, which enables target concentration readings by converting pressure into multiple signals, provides an effective way to visualize POCT assays in resource-limited areas.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Sistemas de Atención de Punto , Oro/química , Peróxido de Hidrógeno/química , Reproducibilidad de los Resultados , Nanopartículas del Metal/química , Límite de Detección , Inmunoensayo
5.
Anal Chem ; 95(13): 5764-5772, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-36961977

RESUMEN

Post-transcriptional regulators, microRNAs (miRNAs), are involved in the occurrence and progression of various diseases. However, due to the complexity of disease-related miRNA regulatory networks, the typing and identification of miRNAs have remained challenging. Herein, a linear ladder-like DNA nanoarchitecture (LDN) was constructed to promote the movement efficiency of the tripedal DNA walker (T-walker), which was combined with the DNA-based logic gates and the PTCDA@PDA/CdS/WO3 photoelectrode to develop a novel biosensor for the detection of dual-miRNAs. Two miRNAs, miR-122 and miR-21, were used as targets to operate the logic module, while its output, trigger strands (TSs), initiated a catalytic hairpin assembly (CHA) reaction to form a T-walker. By using LDN as the track, the T-walker efficiently unfolded hairpin 4, which further hybridized with the alkaline phosphatase-modified hairpin 5 (AP-H5). The remaining AP can catalyze the ascorbic acid 2-phosphate (AAP) into ascorbic acid (AA), an ideal electron donor, thus resulting in a photocurrent change. The photocurrent signals of both AND and OR gates displayed a linear relationship with the logarithm of dual-miRNA concentrations with detection limits of 10.1 and 13.6 fM, respectively. Moreover, the intelligent and rational design of DNA tracks gives impetus to create a well-organized sensing interface with wide application in clinical diagnosis and cancer monitoring.


Asunto(s)
Técnicas Biosensibles , MicroARNs , MicroARNs/genética , ADN/química , Técnicas Biosensibles/métodos , Lógica , Catálisis , Límite de Detección
6.
Anal Chem ; 95(42): 15769-15777, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37734028

RESUMEN

Inspired by the molecular crowding effect in biological systems, a novel heterogeneous quadratic amplification molecular circuit (HEQAC) was developed for sensitive bimodal miRNA profiling (HEQAC-BMP) by combining an MNAzyme-based DNA nanomachine with an entropy-driven catalytic hairpin assembly (E-CHA) autocatalytic circuit. Utilizing ferromagnetic nanomaterials as the substrate for DNA nanomachines, a biomimetic heterogeneous interface was established; thus, a localized molecular crowding system was created that can elevate the local reaction concentration and accelerate the molecular recognition process for a significant threshold signal. Simultaneously, the threshold signal undergoes further amplification by E-CHA and is transformed into a chemical signal, enabling a colorimetric-fluorescence bimodal signal readout. The HEQAC-BMP enables miRNA detection from 10 aM to 10 nM with detection limits of 3.7 aM (colorimetry) and 4.8 aM (fluorometry), respectively. Moreover, the design principle and strategy of HEQAC-BMP can be customized to address other critical viruses or diseases with life-threatening and socioeconomic impacts, enhancing healthcare outcomes for individuals.

7.
J Gene Med ; 25(7): e3498, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36905106

RESUMEN

BACKGROUND: WD repeat domain 3 (WDR3) is involved in tumor growth and proliferation, but its role in the pathological mechanism of prostate cancer (PCa) is still unclear. METHODS: WDR3 gene expression levels were obtained by analyzing databases and our clinical specimens. The expression levels of genes and proteins were determined by a real-time polymerase chain reaction, western blotting and immunohistochemistry, respectively. Cell-counting kit-8 assays were used to measure the proliferation of PCa cells. Cell transfection was used to investigate the role of WDR3 and USF2 in PCa. Fluorescence reporter and chromatin immunoprecipitation assays were used to detect USF2 binding to the promoter region of RASSF1A. Mouse experiments were used to confirm the mechanism in vivo. RESULTS: By analyzing the database and our clinical specimens, we found that WDR3 expression was significantly increased in PCa tissues. Overexpression of WDR3 enhanced PCa cell proliferation, decreased cell apoptosis rate, increased spherical cell number and increased indicators of stem cell-like properties. However, these effects were reversed by WDR3 knockdown. WDR3 was negatively correlated with USF2, which was degraded by promoting ubiquitination of USF2, and USF2 interacted with promoter region-binding elements of RASSF1A to depress PCa stemness and growth. In vivo studies showed that WDR3 knockdown reduced tumor size and weight, reduced cell proliferation and enhanced cell apoptosis. CONCLUSIONS: WDR3 ubiquitinated USF2 and inhibited its stability, whereas USF2 interacted with promoter region-binding elements of RASSF1A. USF2 transcriptionally activated RASSF1A, which inhibited the carcinogenic effect of WDR3 overexpression.


Asunto(s)
Neoplasias de la Próstata , Animales , Humanos , Masculino , Ratones , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/genética , Células Madre , Transfección , Factores Estimuladores hacia 5'/genética
8.
BMC Med ; 21(1): 256, 2023 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-37452335

RESUMEN

BACKGROUND: Genome-wide association studies (GWAS) have reported single-nucleotide polymorphisms (SNPs) in the VRK serine/threonine kinase 2 gene (VRK2) showing genome-wide significant associations with major depression, but the regulation effect of the risk SNPs on VRK2 as well as their roles in the illness are yet to be elucidated. METHODS: Based on the summary statistics of major depression GWAS, we conducted population genetic analyses, epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to identify the functional SNPs regulating VRK2; we also carried out behavioral assessments, dendritic spine morphological analyses, and phosphorylated 4D-label-free quantitative proteomics analyses in mice with Vrk2 repression. RESULTS: We identified a SNP rs2678907 located in the 5' upstream of VRK2 gene exhibiting large spatial overlap with enhancer regulatory marks in human neural cells and brain tissues. Using luciferase reporter gene assays and eQTL analyses, the depression risk allele of rs2678907 decreased enhancer activities and predicted lower VRK2 mRNA expression, which is consistent with the observations of reduced VRK2 level in the patients with major depression compared with controls. Notably, Vrk2-/- mice exhibited depressive-like behaviors compared to Vrk2+/+ mice and specifically repressing Vrk2 in the ventral hippocampus using adeno-associated virus (AAV) lead to consistent and even stronger depressive-like behaviors in mice. Compared with Vrk2+/+ mice, the density of mushroom and thin spines in the ventral hippocampus was significantly altered in Vrk2-/- mice, which is in line with the phosphoproteomic analyses showing dysregulated synapse-associated proteins and pathways in Vrk2-/- mice. CONCLUSIONS: Vrk2 deficiency mice showed behavioral abnormalities that mimic human depressive phenotypes, which may serve as a useful murine model for studying the pathophysiology of depression.


Asunto(s)
Estudio de Asociación del Genoma Completo , Leucemia Mieloide Aguda , Humanos , Ratones , Animales , Depresión/genética , Polimorfismo de Nucleótido Simple , Proteínas Serina-Treonina Quinasas/metabolismo
9.
Eur Radiol ; 33(1): 566-577, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35788755

RESUMEN

OBJECTIVES: To explore the performance of a deep learning-based algorithm for automatic patellofemoral joint (PFJ) parameter measurements from the Laurin view. METHODS: A total of 1431 consecutive Laurin views of the PFJ were retrospectively collected and divided into two parts: (1) the model development dataset (dataset 1, n = 1230) and (2) the hold-out test set (dataset 2, n = 201). Dataset 1 was used to develop the U-shaped fully convolutional network (U-Net) model to segment the landmarks of the PFJ. Based on the predicted landmarks, the PFJ parameters were calculated, including the sulcus angle (SA), congruence angle (CA), patellofemoral ratio (PFR), and lateral patellar tilt (LPT). Dataset 2 was used to assess the model performance. The mean of three radiologists who independently measured the PFJ parameters was defined as the reference standard. Model performance was assessed by the intraclass correlation coefficient (ICC), mean absolute difference (MAD), and root mean square (RMS) compared to the reference standard. Ninety-five percent limits of agreement (95% LoA) were calculated pairwise for each radiologist, reference standard, and model. RESULTS: Compared with the reference standard, U-Net showed good performance for predicting SA, CA, PFR, and LPT, with ICC = 0.85-0.97, MAD = 0.06-5.09, and RMS = 0.09-6.90 in the hold-out test set. Except for the PFR, the remaining parameters measured between the reference standard and the model were within the 95% LoA in the hold-out test dataset. CONCLUSIONS: The U-Net-based deep learning approach had a relatively high model performance in automatically measuring SA, CA, PFR, and LPT. KEY POINTS: • The U-Net model could be used to segment the landmarks of the PFJ and calculate the SA, CA, PFR, and LPT, which could be used to evaluate the patellar instability. • In the hold-out test, the automatic measurement model yielded comparable performance with reference standard. • The automatic measurement model could still accurately predict SA, CA, PFR, and LPT in patients with PI and/or PFOA.


Asunto(s)
Aprendizaje Profundo , Inestabilidad de la Articulación , Articulación Patelofemoral , Humanos , Articulación Patelofemoral/diagnóstico por imagen , Estudios Retrospectivos , Rótula
10.
BMC Urol ; 23(1): 12, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36717806

RESUMEN

BACKGROUND: Numerous studies have shown that local therapy can improve long-term survival in patients with metastatic prostate cancer. However, it is unclear which patients are the potential beneficiaries. METHODS: We obtained information on prostate cancer patients from the Surveillance, Epidemiology, and End Results database and divided eligible patients into the local treatment group and non-local treatment group. Propensity score matching (PSM) was used to reduce the influence of confounding factors. In the matched local treatment (LT) group, if the median overall survival time (OS) was longer than the Nonlocal treatment (NLT) group, it was defined as a benefit group, otherwise, it was a non-benefit group. Then, univariate and multivariate logistic regression were used to screen out predictors associated with benefits, and a nomogram model was constructed based on these factors. The accuracy and clinical value of the models were assessed through calibration plots and decision curve analysis. RESULTS: The study enrolled 7255 eligible patients, and after PSM, each component included 1923 patients. After matching, the median OS was still higher in the LT group than in the NLT group [42 (95% confidence interval: 39-45) months vs 40 (95% confidence interval: 38-42) months, p = 0.03]. The independent predictors associated with benefit were age, PSA, Gleason score, T stage, N stage, and M stage. The nomogram model has high accuracy and clinical application value in both the training set (C-index = 0.725) and the validation set (C-index = 0.664). CONCLUSIONS: The nomogram model we constructed can help clinicians identify patients with potential benefits from LT and formulate a reasonable treatment plan.


Asunto(s)
Nomogramas , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Clasificación del Tumor , Prostatectomía/métodos
11.
Chem Biodivers ; 20(4): e202200949, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36869005

RESUMEN

This study investigated the effect of butanol extract of AS (ASBUE) on atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. The mice were administered ASBUE (390 or 130 mg/kg/day) or rosuvastatin (RSV) via oral gavage for eight weeks. In ApoE-/- mice, ASBUE suppressed the abnormal body weight gain and improved serum and liver biochemical indicators. ASBUE remarkably reduced the aortic plaque area, improved liver pathological conditions, and lipid metabolism abnormalities, and altered the intestinal microbiota structure in ApoE-/- mice. In the vascular tissue of ASBUE-treated mice, P-IKKß, P-NFκB, and P-IκBα levels tended to decrease, while IκB-α increased in high fat-diet-fed atherosclerotic mice. These findings demonstrated the anti-atherosclerotic potential of ASBUE, which is mediated by the interaction between the gut microbiota and lipid metabolism and regulated via the Nuclear Factor-kappa B (NF-κB) pathway. This work paves the groundwork for subsequent studies to develop innovative drugs to treat atherosclerosis.


Asunto(s)
Aterosclerosis , Eleutherococcus , Extractos Vegetales , Animales , Ratones , Apolipoproteínas/genética , Apolipoproteínas E/genética , Aterosclerosis/tratamiento farmacológico , Butanoles , Dieta Alta en Grasa/efectos adversos , Eleutherococcus/química , FN-kappa B/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico
12.
Molecules ; 28(13)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37446750

RESUMEN

Atherosclerosis (AS) is a serious threat to human health and the main pathological basis of cardiovascular disease. Hyperoside (Hyp), a flavonoid found mainly in traditional Chinese herbs, can exert antitumor, anti-inflammatory, antioxidant, and cardiovascular-protective effects. Herein, we prepared hybrid nanomicelles (HFT) comprising Hyp loaded into pluronic F-127 and polyethylene glycol 1000 vitamin E succinate and assessed their effects on AS. To establish an AS model, apolipoprotein-E-deficient (ApoE-/-) mice were fed a high-fat diet. We then analyzed the effects of HFT on AS-induced changes in aortic tissues and metabolic markers, simultaneously assessing changes in gut flora community structure. In mice with AS, HFT significantly reduced the aortic plaque area; decreased levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, inflammatory factors, and inducible nitric oxide synthase (NOS); increased high-density lipoprotein cholesterol, endothelial NOS, superoxide dismutase, catalase, and glutathione levels; and promoted the proliferation of beneficial gut bacteria. HFT could regulate intestinal flora structure and lipid metabolism and inhibit inflammatory responses. These beneficial effects may be mediated by inhibiting nuclear factor kappa B signal activation, reducing inflammatory factor expression and improving gut microflora structure and dyslipidemia. The present study provides an empirical basis for the development and clinical application of new dosage forms of Hyp.


Asunto(s)
Aterosclerosis , Microbioma Gastrointestinal , Ratones , Humanos , Animales , Dieta Alta en Grasa/efectos adversos , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patología , Triglicéridos , LDL-Colesterol , Apolipoproteínas E/genética , Apolipoproteínas , Ratones Endogámicos C57BL , Ratones Noqueados
13.
Compr Rev Food Sci Food Saf ; 22(2): 1285-1311, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36717757

RESUMEN

Mycotoxin contamination in foods and other goods has become a broad issue owing to serious toxicity, tremendous threat to public safety, and terrible loss of resources. Herein, it is necessary to develop simple, sensitive, inexpensive, and rapid platforms for the detection of mycotoxins. Currently, the limitation of instrumental and chemical methods cannot be massively applied in practice. Immunoassays are considered one of the best candidates for toxin detection due to their simplicity, rapidness, and cost-effectiveness. Especially, the field of dual-mode immunosensors and corresponding assays is rapidly developing as an advanced and intersected technology. So, this review summarized the types and detection principles of single-mode immunosensors including optical and electrical immunosensors in recent years, then focused on developing dual-mode immunosensors including integrated immunosensors and combined immunosensors to detect mycotoxins, as well as the combination of dual-mode immunosensors with a portable device for point-of-care test. The remaining challenges were discussed with the aim of stimulating future development of dual-mode immunosensors to accelerate the transformation of scientific laboratory technologies into easy-to-operate and rapid detection platforms.


Asunto(s)
Técnicas Biosensibles , Micotoxinas , Micotoxinas/análisis , Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Alimentos
14.
Anal Chem ; 94(10): 4294-4302, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35107977

RESUMEN

The detection of rosiglitazone (RSG) in food is of great importance since the excessive intake of RSG could cause adverse effects on the human body. Although liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry are the preliminary methods for the detection of hazardous materials in food, they are not suitable for point-of-care or on-site detection. Herein, a time-based readout (TBR) device with an application software (APP) controlled by a smart phone was developed for the sensitive and selective immunoassay of RSG. The homemade TBR device was based on a two-electrode system, where the immune molecule-modified glassy carbon electrode was used as the bioanode, and Prussian blue-modified FTO was used as the cathode. By using Au-modified octahedral Cu2O with high catalytic activity as mimetic peroxidase, an insulating layer was generated on the cathode by catalyzing 4-chloro-1-naphthol (4-CN) into benzo-4-chlorohexadienone (B4Q). The time to reach a fixed potential varied indirectly with the concentrations of RSG and was recognized by the APP, while the electrochromic property on the cathode was also correspondingly changed. Under optimum conditions, both the square root of the time and the chroma value of the electrochromism exhibited linear responses for the detection of RSG ranging from 5 × 10-10 to 5 × 10-7 g/L, while the limits of detection were 8.2 × 10-11 and 1.3 × 10-10 g/L, respectively. With easy operation and portability, this TBR device showed a promising application for point-of-care monitoring of hazardous materials in food or the environment.


Asunto(s)
Técnicas Biosensibles , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Electrodos , Sustancias Peligrosas , Humanos , Inmunoensayo , Rosiglitazona
15.
Anal Chem ; 93(34): 11816-11825, 2021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34461727

RESUMEN

The abnormal expression of microRNA (miRNA) can affect the RNA transcription and protein translation, leading to tumor progression and metastasis. Currently, the accurate detection of aberrant expression of miRNA, particularly using a portable detection system, remains a great challenge. Herein, a novel dual-mode biosensor with high sensitivity and robustness for miR-21 detection was developed based on the cis-cleavage and trans-cleavage activities of Cas12a. miRNA can be combined with hairpin DNA-horseradish peroxidase anchored on a CdS/g-C3N4/B-TiO2 photoelectrode, thus the nonenzymatic amplification was triggered to form numerous HRP-modified double-stranded DNA (HRP-dsDNA). Then, HRP-dsDNA can be specifically recognized and efficiently cis-cleaved by Cas12a nucleases to detach HRP from the substrate, while the remaining HRP on HRP-dsDNA can catalyze 4-chloro-1-naphthol (4-CN) to form biocatalytic precipitation (BCP) on the surface of the photoelectrode, and thus the photocurrent can be changed. Meanwhile, the trans-cleavage ability of Cas12a was activated, and nonspecifically degrade the FQ-reporter and a significant fluorescence signal can be generated. Such two different kinds of signals with independent transmission paths can mutually support to improve the performance of the detection platform. Besides, a portable device was constructed for the point-of-care (POC) detection of miR-21. Moreover, the dual-mode detection platform can be easily expanded for the specific detection of other types of biomarkers by changing the sequence of hairpin DNA, thereby promoting the establishment of POC detection for early cancer diagnosis.


Asunto(s)
Técnicas Biosensibles , MicroARNs , Sistemas CRISPR-Cas , ADN , Peroxidasa de Rábano Silvestre , MicroARNs/genética
16.
Mol Psychiatry ; 25(1): 48-66, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31723243

RESUMEN

Schizophrenia and bipolar disorder (BPD) are believed to share clinical features, etiological factors, and disease pathologies (such as impaired cognitive functions and dendritic spine pathology). Meanwhile, there is growing evidence of shared genetic risk between schizophrenia and BPD, despite that our knowledge of the functional risk variations and biological mechanisms is still limited. Here, we conduct summary data-based Mendelian randomization (SMR) analyses through combining the statistical data from genome-wide association studies (GWAS) of both schizophrenia and BPD and multiple expression quantitative trait loci (eQTL) datasets of the human brain dorsolateral prefrontal cortex (DLPFC) tissues. These integrative investigations identify a lead risk locus at the chromosome 3p21.1 region, which contains numerous single-nucleotide polymorphisms (SNPs) in varied linkage disequilibrium (LD) and encompasses more than 20 genes. Further analyses suggest that many SNPs at 3p21.1 are significantly associated with both schizophrenia and BPD, and even depression, and the psychiatric risk alleles at 3p21.1 are correlated with mRNA expression of multiple genes such as NEK4, GNL3, and PBRM1. We also identify a 335-bp functional Alu polymorphism rs71052682 in significant LD with the psychiatric GWAS risk SNP rs2251219, and confirm the regulatory effects of this Alu polymorphism on transcription activities. We then explore the involvement of the 3p21.1 locus in the common clinical features and etiology of these illnesses. We reveal that psychiatric risk alleles at 3p21.1 in low-to-high LD consistently predict worse cognitive functions in humans, and manipulating the gene expression (NEK4, GNL3, and PBRM1) linked with higher genetic risk could reduce the density of mushroom dendritic spines in rat primary cortical neurons, mirroring the spine pathology in the prefrontal cortex of psychiatric patients. Our results find that, although the risk alleles at 3p21.1 are in low-to-moderate LD spanning a large genomic area, their underlying biological mechanisms in psychiatric disorders likely converge. These results provide essential insights into the neural mechanisms underlying the chromosome 3p21.1 risk locus in the shared pathological and etiological features of both schizophrenia and BPD.


Asunto(s)
Cromosomas Humanos Par 3/genética , Expresión Génica/genética , Trastornos Mentales/genética , Alelos , Animales , Trastorno Bipolar/genética , Línea Celular , Cognición/fisiología , Bases de Datos Genéticas , Espinas Dendríticas/genética , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Trastornos Mentales/metabolismo , Polimorfismo de Nucleótido Simple/genética , Sitios de Carácter Cuantitativo/genética , Ratas , Ratas Sprague-Dawley , Factores de Riesgo , Esquizofrenia/genética
17.
Neurourol Urodyn ; 40(6): 1593-1599, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34058024

RESUMEN

BACKGROUND: The controversy on the best surgical approach for vesicovaginal fistula (VVF) repair remains due to the scarcity of high-level evidences. We aim to analyze the efficacy and safety of the laparoscopic transvesical (LT) and laparoscopic extravesical (LE) approaches to posthysterectomy VVF (PH-VVF). METHODS: Data of 64 patients with PH-VVFs who were laparoscopicly treated in the First Affiliated Hospital of Nanchang University and the Hangzhou Third Hospital from January 2011 to November 2019 were retrospectively collected. The operative time (OT), estimated bleeding volume (EBV), postoperative bladder function and complications, hospital stay length (HSL), surgery success rate, and recurrence were compared between the two groups. RESULTS: In all, there were no significant differences in baseline characteristics between those two arms. Both approaches were successfully performed without open conversion in either group. The LT group was significantly corrected with a shorter mean OT than the LE group (p < 0.001), regardless of the fistula's position. No significant differences existed in the mean EBV and HSL between the two interventions (p = 0.136 and p = 0.210, respectively). The tendency of postoperative complications and success rates of surgery were also comparable in both groups. The patients in the LT group had similar bladder functions to those in LE group. The recurrence occurred in one patient in each arm during the follow-up periods of 12-36 months. CONCLUSIONS: The LT approach is significantly related to a shorter OT than the LE approach without compromising the safety and success rates in repairing PH-VVF.


Asunto(s)
Laparoscopía , Fístula Vesicovaginal , Femenino , Hospitales , Humanos , Laparoscopía/efectos adversos , Tempo Operativo , Estudios Retrospectivos , Fístula Vesicovaginal/etiología , Fístula Vesicovaginal/cirugía
18.
Mikrochim Acta ; 188(3): 62, 2021 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-33534035

RESUMEN

A multi-colorimetric immunosensor basing on the mimetic enzyme etching of gold nanobipyramids (Au NBPs) was established to detect ochratoxin A (OTA). Octahedral Cu2O nanoparticles were successfully synthesized through a selective surface stabilization strategy, which can exhibit a peroxidase-like ability to oxidize 3,3',5,5'-tetramethylbenzidine (TMB). Au NBPs can be etched by the product, TMB2+, to form a significant longitudinal peak blue shift of local surface plasmon resonance. During the construction of the immunosensor, the microplate was coated with dopamine to immobilized OTA antigens, followed by the immunoreaction of OTA antibody and the Cu2O-labled secondary antibody. A linear relationship can be found between the local surface plasmon resonance (LSPR) peak changes with the logarithm of OTA concentration in a wide range from 1 ng/L to 5 µg/L, while the detection limit was 0.47 ng/L. Meanwhile, the approximate OTA concentration can be conveniently and intuitively observed by the vivid color changes. Benefiting from the high specificity, the proposed multi-colorimetric immunoassay detection of OTA in millet samples was achieved, indicating the available potential of the immunoassay for the determination of OTA in real samples.


Asunto(s)
Colorimetría/métodos , Inmunoensayo/métodos , Nanopartículas del Metal/química , Ocratoxinas/análisis , Anticuerpos/química , Anticuerpos/inmunología , Bencidinas/química , Compuestos Cromogénicos/química , Cobre/química , Contaminación de Alimentos/análisis , Oro/química , Peróxido de Hidrógeno/química , Límite de Detección , Mijos/química , Ocratoxinas/inmunología , Oxidación-Reducción
19.
BJU Int ; 126(2): 300-308, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32402143

RESUMEN

OBJECTIVES: To describe in detail the techniques for transvesical robot-assisted radical prostatectomy (RARP) using the da Vinci Si/Xi system (Intuitive Surgical, Sunnyvale, CA, USA) and to evaluate functional and oncological outcomes in 35 patients with prostate cancer. PATIENTS AND METHODS: Thirty-five patients with localized prostate cancer were enrolled for transvesical RARP. The patients' preoperative data (mean ± sd age 63.4 ± 8.1 years, body mass index 28.6 ± 5.3 kg/m2 , total prostate-specific antigen 10.8 ± 4.9 ng/mL and prostate volume 30.6 ± 14.4 mL, and median [interquartile range {IQR}] biopsy Gleason score 6 [6-7], and International Index of Erectile Function [IIEF]-5 score 18 [16-20]) were collected. Preoperative assessment revealed 28 cases of cT2a and seven cases of cT2b disease. All patients were continent preoperatively (defined as no pad required or one dry pad per day as a precaution). Surgical results and peri-operative complications were assessed. All patients were followed up for at least 12 months postoperatively. RESULTS: The mean operating time was 150 ± 35 min. Estimated blood loss was 100 ± 45 mL. Urinary infection was noted in one patient and managed with levofloxacin. Another patient complained of nocturia on postoperative day 14, which was relieved with solifenacin succinate. Urethral catheters were removed on postoperative day 7. Thirty-two patients achieved immediate urinary continence, with three patients returning to full continence on postoperative day 14. Postoperative pathology confirmed 24 pT2a cases, nine pT2b cases and two pT2c cases (median [IQR] Gleason score 6 [6-7]). Positive surgical margins were found in four patients (11.4%). No urethral stricture or urinary leakage was noted on urethrocystography taken 3 months after surgery. Urodynamic studies were performed preoperatively and 6 months after surgery: median (IQR) maximum urinary flow 12.2 (10.2-14.9) vs 13.7 (10.1-15.0) mL/s; bladder capacity 385.3 (351.3-410.2) vs 370.2 (330.1-395.4) mL; and voiding phase detrusor contractility 38.5 (27.8-42.3) vs 35.6 (28.3-41.3) mmH2 O, respectively. During a minimum of 12 months of follow-up, no biochemical recurrence was noted in any patient. The median (IQR) IIEF-5 score was 17 (16-19). CONCLUSIONS: The transvesical approach is a valid alternative to RARP in selected patients, providing promising postoperative urinary continence. Long-term functional and oncological results require further investigation.


Asunto(s)
Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Procedimientos Quirúrgicos Robotizados , Anciano , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vejiga Urinaria
20.
Nanotechnology ; 31(20): 205403, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32000156

RESUMEN

As a substitute of Pt-based catalysts, MoS2-based catalysts have been widely used in hydrogen evolution reaction, but the inherent low conductivity, limited active edges, self-stacking and agglomeration still hinder their activities. In this work, Mn-doped MoS2 nanosheets were vertically anchored on carbon nanotubes (CNTs) by the one-step hydrothermal reaction, in which Mn-O-C/Mo-O-C was considered as a bridge between Mn-MoS2 and CNTs. The doping of the Mn element enables the spreading of MoS2 on CNTs and the rapid escape of hydrogen bubbles from the electrode, while conductive CNTs with hydrophilicity can accelerate the electron transport process between the electrolyte and the material. With an overpotential of 150 mV at a current density of -10 mA cm-2 and a Tafel slope of 39 mV dec-1, this material exhibited excellent catalytic hydrogen evolution activity, which could open the path for designing commercial electrocatalysts.

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