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1.
PeerJ ; 12: e17916, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39193514

RESUMEN

Background: Aberrant DNA methylation patterns play a critical role in the development of hepatocellular carcinoma (HCC). However, the molecular mechanisms associated with these aberrantly methylated genes remain unclear. This study aimed to comprehensively investigate the methylation-driven gene expression alterations in HCC using a multi-omics dataset. Methods: Whole genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) techniques were used to assess the methylation and gene expression profiles of HCC tissues (HCCs) and normal adjacent tissues (NATs). The candidate genes' potential function was further investigated using single-cell RNA sequencing (scRNA seq) data. Results: We observed widespread hypomethylation in HCCs compared to NATs. Methylation levels in distinct genomic regions exhibited significant differences between HCCs and NATs. We identified 247,632 differentially methylated regions (DMRs) and 4,926 differentially expressed genes (DEGs) between HCCs and NATs. Integrated analysis of DNA methylation and RNA-seq data identified 987 methylation-driven candidate genes, with 970 showing upregulation and 17 showing downregulation. Four genes involved in the retinol metabolic pathway, namely ADH1A, CYP2A6, CYP2C8, and CYP2C19, were identified as hyper-downregulated genes. Their expression levels could stratify HCCs into three subgroups with distinct survival outcomes, immune cell infiltration, and tumor microenvironments. Validation of these findings in an independent dataset yielded similar outcomes, confirming the high concordance and potential prognostic value of these genes. ScRNA seq data revealed the low expression of these genes in immune cells, emphasizing their role in promoting malignant cell proliferation and migration. In conclusion, this study provides insights into the molecular characteristics of HCC, revealing the involvement of retinol metabolism-related genes in the development and progression of HCC. These findings have implications for HCC diagnosis, prognosis prediction, and the development of therapeutic targets.


Asunto(s)
Carcinoma Hepatocelular , Metilación de ADN , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Vitamina A , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Vitamina A/metabolismo , Femenino , Masculino
2.
J Formos Med Assoc ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39183142

RESUMEN

AIMS: This study aimed to assess the accuracy of a two-protein panel for mismatch repair (MMR) immunohistochemistry (IHC) compared to a four-protein panel in a cohort of endometrial cancer patients. METHODS: The study included patients diagnosed with endometrial cancer between January 2018 and December 2023 with patients underwent MMR IHC staining for the four-protein panel (MSH2, MSH6, MLH1, and PMS2) serving as the reference standard. Various combinations of two proteins were examined and evaluated for their accuracy against the four-protein panel. Sensitivity, negative predictive value (NPV), and negative likelihood ratio were calculated for each combination. McNemar's test was performed to assess discordance, and receiver operating characteristic (ROC) curves were generated to evaluate diagnostic accuracy. RESULTS: Of 593 patients, MMR deficiency defined as at least one protein loss was observed in 146 patients (24.62%). When compared with four-protein panel, the highest sensitivity was observed with the MSH6/PMS2 combination (99.32%), followed sequentially by MSH6/MLH1 (97.26%), MSH2/PMS2 (93.15%), MSH2/MLH1 (91.10%), MLH1/PMS2 (79.45%), and MSH2/MSH6 (21.92%). The MSH6/PMS2 combination also demonstrated the best NPV of 99.78% and negative likelihood ratio of 0.01, while MSH6/MLH1 showed satisfactory NPV of 99.11% and negative likelihood ratio of 0.03. McNemar's test revealed no statistical difference between the four-protein panel and the MSH6/PMS2 panel (p = 1.000), and the MSH6/MLH1 panel (p = 0.125). CONCLUSIONS: The two-protein panel, particularly MSH6/PMS2, offers high sensitivity and negative predictive value, suggesting its potential as a cost-effective alternative to the four-protein panel in MMR testing for endometrial cancer patients.

3.
Biosens Bioelectron ; 262: 116556, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38996596

RESUMEN

The multiple-readout capability of multimodal detection enhances the flexibility, reliability, and accuracy of lateral flow immunoassay (LFIA). The conjugation of two different metal-organic frameworks (MOFs) as a new-generation composite material offers extraordinary opportunities for developing multimodal LFIA. It is anticipated to compensate limitations of traditional single colorimetric signal LFIA and improve the analysis performance. Herein, an ultra-bright fluorescent AIE-MOF was proposed and coupled with an in-situ growth of Prussian blue (PB) nanoparticles strategy to obtain a novel multimodal signal tracer (AIE-MOF@PB). Thereafter, it was successfully applied to develop the multimodal LFIA platform for the detection of nitrofurazone metabolites. The synergy of AIE-MOF and PB endows AIE-MOF@PB with superb water dispersibility, robust fluorescence emission, brilliant colorimetric signal, marvelous photothermal conversion, and enhanced antibody coupling efficiency, all of which facilitate a highly sensitive triple-readout LFIA platform. The detection sensitivity improved by at least 5-fold compared with the colloidal gold-based LFIA. This work not only inspires the rational design of aggregation-induced emission luminogens (AIEgen)-based complex materials but also highlights the promising potential in flexible point-of-care applications.


Asunto(s)
Técnicas Biosensibles , Límite de Detección , Estructuras Metalorgánicas , Nitrofurazona , Estructuras Metalorgánicas/química , Inmunoensayo/métodos , Inmunoensayo/instrumentación , Técnicas Biosensibles/métodos , Nitrofurazona/análisis , Nitrofurazona/química , Humanos , Ferrocianuros/química , Colorimetría/métodos , Colorantes Fluorescentes/química
4.
Eur J Med Chem ; 274: 116543, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38823265

RESUMEN

Colchicine binding site inhibitors (CBSIs) have attracted much attention due to their antitumor efficacies and the advantages of inhibiting angiogenesis and overcoming multidrug resistance. However, no CBSI has been currently approved for cancer treatment due to the insufficient efficacies, serious toxicities and poor pharmacokinetic properties. Design of dual-target inhibitors is becoming a potential strategy for cancer treatment to improve anticancer efficacy, decrease adverse events and overcome drug resistance. Therefore, we reviewed dual-target inhibitors of colchicine binding site (CBS), summarized the design strategies and the biological activities of these dual-target inhibitors, expecting to provide inspiration for developing novel dual inhibitors based on CBS.


Asunto(s)
Antineoplásicos , Colchicina , Neoplasias , Humanos , Colchicina/metabolismo , Colchicina/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Sitios de Unión/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/uso terapéutico , Estructura Molecular , Animales
5.
Lab Chip ; 24(8): 2272-2279, 2024 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-38504660

RESUMEN

A highly sensitive lateral flow immunoassay (LFIA) is developed for the enzyme-catalyzed and double-reading determination of clenbuterol (CLE), in which a new type of probe was adopted through the direct electrostatic adsorption of ultra-small copper-gold bimetallic enzyme mimics (USCGs) and monoclonal antibodies. In the assay, based on the peroxidase activity of USCG, the chromogenic substrate TMB-H2O2 was introduced to trigger its color development, and the results were compared with those before catalysis. The detection sensitivity after catalysis is 0.03 ng mL-1 under optimal circumstances, which is 6-fold better than that of the traditional Au NPs-based LFIA and 2-fold greater than that before catalysis. This approach was successfully applied to the detection of CLE in milk, pork and mutton samples with an optimum assay time of 7 min and best catalytic time of 80 s, after which satisfactory recoveries of 98.53-117.79% were obtained. Cu-Au nanoparticles as a signal tag and the use of their nanozyme properties are the first applications in the field of LFIA. This work can be a promising exhibition for the application of a cheaper substitute for HRP, ultra-small bimetallic enzyme mimics, in LFIAs.


Asunto(s)
Clenbuterol , Nanopartículas del Metal , Límite de Detección , Cobre , Oro/química , Peróxido de Hidrógeno , Nanopartículas del Metal/química , Catálisis , Inmunoensayo/métodos
6.
Anal Chem ; 96(12): 5046-5055, 2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38488055

RESUMEN

Bimodal-type multiplexed immunoassays with complementary mode-based correlation analysis are gaining increasing attention for enhancing the practicability of the lateral flow immunoassay (LFIA). Nonetheless, the restriction in visually indistinguishable multitargets induced by a single fluorescent color and difficulty in single acceptor ineffectual fluorescence quenching due to the various spectra of multiple different donors impede the further execution of colorimetric-fluorescence bimodal-type multiplexed LFIAs. Herein, the precise spectral overlap-based donor-acceptor pair construction strategy is proposed by regulating the size of the nanocore, coating it with an appropriate nanoshell, and selecting a suitable fluorescence donor with distinct colors. By in situ coating Prussian blue nanoparticles (PBNPs) on AuNPs with a tunable size and absorption spectrum, the resultant APNPs demonstrate efficient fluorescence quenching ability, higher colloidal stability, remarkable colorimetric intensity, and an enhanced antibody coupling efficiency, all of which facilitate highly sensitive bimodal-type LFIA analysis. Following integration with competitive-type immunoreaction, this precise spectral overlap-supported spatial separation traffic light-typed colorimetric-fluorescence dual-response assay (coined as the STCFD assay) with the limits of detection of 0.013 and 0.152 ng mL-1 for ractopamine and clenbuterol, respectively, was proposed. This work illustrates the superiority of the rational design of a precise spectral overlap-based donor-acceptor pair, hinting at the enormous potential of the STCFD assay in the point-of-care field.


Asunto(s)
Clenbuterol , Nanopartículas del Metal , Oro , Inmunoensayo , Fenómenos Químicos , Límite de Detección
7.
Eur J Med Chem ; 267: 116203, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38342014

RESUMEN

BACKGROUND: Quercetin is widely distributed in nature and abundant in the human diet, which exhibits diverse biological activities and potential medical benefits. However, there remains a lack of comprehensive understanding about its cellular targets, impeding its in-depth mechanistic studies and clinical applications. PURPOSE: This study aimed to profile protein targets of quercetin at the proteome level. METHODS: A label-free CETSA-MS proteomics technique was employed for target enrichment and identification. The R package Inflect was used for melting curve fitting and target selection. D3Pocket and LiBiSco tools were used for binding pocket prediction and binding pocket analysis. Western blotting, molecular docking, site-directed mutagenesis and pull-down assays were used for target verification and validation. RESULTS: We curated a library of direct binding targets of quercetin in cells. This library comprises 37 proteins that show increased thermal stability upon quercetin binding and 33 proteins that display decreased thermal stability. Through Western blotting, molecular docking, site-directed mutagenesis and pull-down assays, we validated CBR1 and GSK3A from the stabilized protein group and MAPK1 from the destabilized group as direct binding targets of quercetin. Moreover, we characterized the shared chemical properties of the binding pockets of quercetin with targets. CONCLUSION: Our findings deepen our understanding of the proteins pivotal to the bioactivity of quercetin and lay the groundwork for further exploration into its mechanisms of action and potential clinical applications.


Asunto(s)
Proteoma , Quercetina , Humanos , Quercetina/farmacología , Quercetina/química , Simulación del Acoplamiento Molecular , Proteoma/metabolismo , Espectrometría de Masas
8.
MedComm (2020) ; 5(2): e494, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38405059

RESUMEN

Lung tissue has a certain regenerative ability and triggers repair procedures after injury. Under controllable conditions, lung tissue can restore normal structure and function. Disruptions in this process can lead to respiratory system failure and even death, causing substantial medical burden. The main types of respiratory diseases are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS). Multiple cells, such as lung epithelial cells, endothelial cells, fibroblasts, and immune cells, are involved in regulating the repair process after lung injury. Although the mechanism that regulates the process of lung repair has not been fully elucidated, clinical trials targeting different cells and signaling pathways have achieved some therapeutic effects in different respiratory diseases. In this review, we provide an overview of the cell type involved in the process of lung regeneration and repair, research models, and summarize molecular mechanisms involved in the regulation of lung regeneration and fibrosis. Moreover, we discuss the current clinical trials of stem cell therapy and pharmacological strategies for COPD, IPF, and ARDS treatment. This review provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials.

9.
Food Chem ; 441: 138374, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38219366

RESUMEN

In this work, an ultra-sensitive lateral flow immunoassay (LFIA) with SERS/colorimetric dual signal mode was constructed for the detection of nitrofurazone metabolites, an antibiotic prohibited in animal-origin foods. Au@4-MBN@AgNRs nano-sandwich structural signal tag integrates the unique advantages of high signal-to-background ratio and anti-matrix interference through geometric control of SERS tag and nanoengineering adjustment of chemical composition. Under the optimal conditions, the detection limits of nitrofurazone metabolites by SERS/colorimetric dual-mode LFIA were 20 pg/mL (colorimetric mode) and 0.08 pg/mL (SERS mode). Excitingly, the vLOD of the colorimetric signal improved by a factor of 100 compared to Au NPs-based LFIA. In this study, the proposed dual-mode LFIA was successfully applied to the on-site real-time detection of honey, milk powder, and chicken. It is anticipated that with low background interference and anti-matrix interference output signal, our proposed dual-mode strategy can pave an innovative pathway for the fabrication of a powerful biosensor.


Asunto(s)
Nanopartículas del Metal , Nitrofurazona , Animales , Oro/química , Inmunoensayo , Antibacterianos , Colorimetría , Nanopartículas del Metal/química , Límite de Detección , Espectrometría Raman
10.
Epigenetics ; 19(1): 2299044, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38154055

RESUMEN

Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals). The combination of G protein subunit beta 4 (GNB4) and Riplet had the optimal area under the curve (AUC) in seven candidates through TCGA, GEO, and WGBS analyses. In tissue validation, the GNB4 and Riplet showed an AUC of 100% with a sensitivity and specificity of 100% for detecting any-stage HCC. In plasma, it demonstrated a high sensitivity of 84.39% at 91.92% specificity, with an AUC of 92.51% for detecting any-stage HCC. The dual-marker panel had a higher sensitivity of 78.26% for stage I HCC than alpha-fetoprotein (AFP) of 47.83%, and a high sensitivity of 70.27% for detecting a single tumour (size ≤3 cm). In conclusion, we developed a novel dual-marker panel that demonstrates high accuracy in detecting HCC, surpassing the performance of AFP testing.


Asunto(s)
Carcinoma Hepatocelular , Subunidades beta de la Proteína de Unión al GTP , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Biomarcadores de Tumor/metabolismo , Metilación de ADN , Subunidades beta de la Proteína de Unión al GTP/genética , Subunidades beta de la Proteína de Unión al GTP/metabolismo
11.
Polymers (Basel) ; 15(22)2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-38006069

RESUMEN

The introduction of polar functional groups into polyolefin chain structures creates opportunities to enhance specific properties, such as adhesion, dyeability, printability, compatibility, thermal stability, and electrical conductivity, which widen the range of potential applications for these modified materials. Transition metal catalysts, especially late transition metals, have proven to be highly effective in copolymerization processes due to their reduced Lewis acidity and electrophilicity. However, when compared to the significant progress and summary of synthetic methods, there is a distinct lack of a comprehensive summary of mechanistic studies pertaining to the catalytic systems involved in ethylene copolymerization catalyzed by palladium and nickel catalysts. In this review, we have provided a comprehensive summary of the latest developments in mechanistic studies of ethylene copolymerization with polar monomers catalyzed by late-transition-metal complexes. Experimental and computational methods were employed to conduct a detailed investigation of these organic and organometallic systems. It is mainly focused on ligand substitution, changes in binding modes, ethylene/polar monomer insertion, chelate opening, and ß-H elimination. Factors that control the catalytic activity, molecular weight, comonomer incorporation ratios, and branch content are analyzed, these include steric repulsions between ligands and monomers, electronic effects arising from both ligands and monomers, and so on.

12.
Anal Chem ; 95(46): 16958-16966, 2023 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-37942854

RESUMEN

Developing signal tracers (STAs) with large size, multifunctionality, and high retention bioaffinity is believed to be a potential solution for achieving high-performance immunochromatographic assays (ICAs). However, the size limitations of STAs on strips are always a challenge because of the serious steric hindrance. Here, based on metal-quinone coordination and further metal etching, hollow micron-tubular STAs formed by natural alizarin and Fe3+ ions (named ALIFe) are produced to break through size limitations, provide more active sites, and achieve three-mode ICAs (ALIFe STAs-ICAs). Thanks to the special tubular morphology, ALIFe can successfully pass through the strip and provide an ideal signal intensity within 7 min at low mAb and probe dosages to achieve stable ICA analysis. Importantly, ALIFe shows excellent antibody enrichment and bioaffinity retention capability. With a proof-of-concept for streptomycin, the ALIFe STAs-ICAs showed the limit of detection (LOD) at 0.39 ng mL-1 for colorimetric mode, 0.32 ng mL-1 for catalytic mode, and 0.016 ng mL-1 for photothermal mode with total recoveries ranging from 80.46 to 121.59% in mike and honey samples. We anticipate that our study will help expand the ideas for the design of high-performance STAs with large size and broaden the practical application of ICA.


Asunto(s)
Antibacterianos , Nanopartículas del Metal , Cromatografía de Afinidad/métodos , Límite de Detección , Nanopartículas del Metal/química
13.
Nano Lett ; 23(20): 9563-9570, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37819937

RESUMEN

Traditional disposable personal protective equipment (PPE) only blocks pathogenic bacteria by mechanical filtration, with the risk of recontamination and transmission remaining. Herein, inspired by phenolic-enabled nanotechnology (PEN), we proposed engineered polyphenol coatings by plant-derived aromatic aldehydes and metal involvement, denoted as FQM, to obtain the desired photocatalysis-self-Fenton antibacterial performance. Experiments and theoretical analysis proved the dual mechanism of Fe-induced enhancement: (1) tuning of molecular structure realized improved optical properties; (2) Fe(III)/Fe(II) triggered photocatalytic cascade self-Fenton reaction. Mechanism study reveals FQM killing bacteria by direct-contact ROS attack and gene regulation. Further, the FQM was developed as the ideal antibacterial coating on different fabrics (cloth cotton, polyester, and N95 mask), killing more than 93% of bacteria after 5 cycles of use. Such photocatalysis-self-Fenton coatings based on engineered polyphenols endowed with desirable safety, sustainability, and efficient antibacterial features are promising solutions to meet the challenges of the currently available PPE.


Asunto(s)
Compuestos Férricos , Polifenoles , Polifenoles/farmacología , Polifenoles/química , Textiles , Antibacterianos/farmacología , Antibacterianos/química
14.
NPJ Biofilms Microbiomes ; 9(1): 63, 2023 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-37679355

RESUMEN

Bacterial biofilms, which consist of three-dimensional extracellular polymeric substance (EPS), not only function as signaling networks, provide nutritional support, and facilitate surface adhesion, but also serve as a protective shield for the residing bacterial inhabitants against external stress, such as antibiotics, antimicrobials, and host immune responses. Biofilm-associated infections account for 65-80% of all human microbial infections that lead to serious mortality and morbidity. Tremendous effort has been spent to address the problem by developing biofilm-dispersing agents to discharge colonized microbial cells to a more vulnerable planktonic state. Here, we discuss the recent progress of enzymatic eradicating strategies against medical biofilms, with a focus on dispersal mechanisms. Particularly, we review three enzyme classes that have been extensively investigated, namely glycoside hydrolases, proteases, and deoxyribonucleases.


Asunto(s)
Biopelículas , Matriz Extracelular de Sustancias Poliméricas , Humanos , Antibacterianos , Plancton , Transducción de Señal
15.
Int J Gynecol Pathol ; 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37732995

RESUMEN

Loss of estrogen receptor/progesterone receptor (ER/PR) in endometrial cancer (EC) is associated with tumor progression and poor outcomes. Elevated pretreatment cancer antigen 125 (CA 125) level is a risk factor for lymph node metastasis (LNM). We evaluated whether the combination of ER/PR expression and CA 125 level could be used as a biomarker to predict LNM. We retrospectively investigated patients with endometrioid EC who underwent complete staging surgery during January 2015 to December 2020. We analyzed ER/PR status using immunohistochemical staining, and quantified its expression using the sum of both ER/PR H-scores. Receiver operating characteristic curves were used to identify optimal cutoff values of H-score and CA 125 levels for predicting LNM. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. In 396 patients, the optimal cutoff values of the ER/PR H-score and CA 125 were 407 (area under the receiver operating characteristic curve: 0.645, P=0.001) and 40 U/mL (area under the receiver operating characteristic curve: 0.762, P<0.001), respectively. Multivariate analysis showed that CA 125 ≥40 UmL (odds ratio: 10.02; 95% CI: 4.74-21.18) and ER/PR H-score <407 (odds ratio: 4.20; 95% CI: 1.55-11.32) were independent predictors. An LNM predictive nomogram was constructed using these 2 variables and our model yielded a negative predictive value and negative likelihood ratio of 98.3% and 0.14, respectively. ER/PR expression with pretreatment CA 125 levels can help estimate LNM risk and aid in decision-making regarding the need for lymphadenectomy in patients with endometrioid EC.

16.
Eur J Med Chem ; 259: 115704, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37544186

RESUMEN

Limonoids, a class of abundant natural tetracyclic triterpenoids, present diverse biological activity and provide a versatile platform amenable by chemical modifications for clinical use. Among all of the limonoids isolated from natural sources, obacunone, nomilin, and limonin are the primary hub of limonoid-based chemical modification research. To date, more than 800 limonoids analogs have been synthesized, some of which possess promising biological activities. This review not only discusses the synthesis of limonoid derivatives as promising therapeutic candidates and details the pharmacological studies of their underlying mechanisms from 2002 to 2022, but also proposes a preliminary limonoid synthetic structure-activity relationship (SAR) and provides future direction of limonoid derivatization research.


Asunto(s)
Limoninas , Triterpenos , Limoninas/farmacología , Limoninas/química , Triterpenos/química , Relación Estructura-Actividad
17.
J Cancer Res Clin Oncol ; 149(13): 11807-11813, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37405474

RESUMEN

PURPOSE: To investigate whether the cost-effective, pretreatment tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) can be used to predict lymph node metastasis (LNM) in endometrioid-type endometrial cancer (EC) and to develop a predictive model. METHODS: This was a single-center retrospective study of patients with endometrioid-type EC who underwent complete staging surgery between January 2015 and June 2022. We identified the optimal cut-off values of CEA and CA-125 for predicting LNM using receiver operating characteristic (ROC) curves. Stepwise multivariate logistic regression analysis was used to identify independent predictors. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. RESULTS: The optimal cut-off values of CEA and CA-125 were 1.4 ng/mL (area under the ROC curve (AUC) 0.62) and 40 U/mL (AUC 0.75), respectively. Multivariate analysis showed that CEA (odds ratio (OR) 1.94; 95% confidence interval (CI) 1.01-3.74) and CA-125 (OR 8.75; 95% CI 4.42-17.31) were independent predictors of LNM. Our nomogram showed adequate discrimination with a concordance index of 0.78. Calibration curves for the probability of LNM showed optimal agreement between the predicted and actual probabilities. The risk of LNM for markers below the cut-offs was 3.6%. The negative predictive value and negative likelihood ratio were 96.6% and 0.26, respectively, with moderate ability to rule out the possibility of LNM. CONCLUSION: We report a cost-effective method of using pretreatment CEA and CA-125 levels to identify patients with endometrioid-type EC who are at a low risk for LNM, which may guide decision-making regarding aborting lymphadenectomy.


Asunto(s)
Carcinoma Endometrioide , Neoplasias Endometriales , Femenino , Humanos , Antígeno Carcinoembrionario , Estudios Retrospectivos , Antígeno Ca-125 , Metástasis Linfática/patología , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Carcinoma Endometrioide/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología
18.
Anal Chem ; 95(8): 4095-4103, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36780295

RESUMEN

It is of great importance to overcome potential incompatibility problems between dyestuffs and antibodies (mAbs) for extensive commercial application of a dyestuff-chemistry-based ultrafast colorimetric lateral flow immunoassay (cLFIA). Herein, inspired by traditional staining technologies, a basic dyestuff gallocyanine (GC)-assisted biogenic "potential scalpel"-based cLFIA (GC-ABPS-based cLFIA) by employing clenbuterol (CLE) as proof-of-concept was proposed to solve a high degree of incompatibility between the same potential dyestuffs and mAbs. Goat antimouse immunoglobulin (Ab2) could serve as the "potential scalpel" to form the positive potential value biomolecular network self-assemblers (BNSA) with anti-CLE mAbs (AbCLE) by noncovalent force. The cLFIA completed the entire detection process from de novo to detection results within 30 min thanks to the easy availability and ideal marking efficiency (≤1 min, saving 0.4-10 h) of GC. Encouragingly, the proposed ultrafast GC-ABPS-based cLFIA has also exhibited high sensitivity (0.411 ng mL-1) and low cost (300 times) compared with other cLFIAs. Also, the feasibility of the proposed cLFIA was demonstrated by detecting CLE in beef, pork ham, and skim milk. Finally, the proposed GC-ABPS-based cLFIA has broadened the application range of dyestuffs and provided an effective reference strategy for the application of dyestuffs in food safety monitoring.


Asunto(s)
Clenbuterol , Animales , Bovinos , Inmunoensayo/métodos , Inocuidad de los Alimentos , Anticuerpos Monoclonales
19.
Anal Chem ; 95(7): 3769-3778, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36757057

RESUMEN

Expanding sensing modes and improving catalytic performance of nanozyme-based analytical chemistry are beneficial to realizing the desired biosensing of analytes. Herein, Schiff-base chemistry coupled with a novel catechol oxidase-like nanozyme (CHzyme) is designed and constructed, exhibiting two main advantages, including (1) improving catalytic performance by nearly 2-fold compared with only the oxidase-like role of CHzyme; (2) increasing the designability of the output signal by signal transduction of cascade reaction. Thereafter, the substrate sensing modes based on a cascade reaction between the CHzyme-catalyzed reaction and Schiff-base chemistry are proposed and comprehensively studied, containing catalytic substrate sensing mode, competitive substrate sensing mode, and generated substrate sensing mode, expecting to be employed in environmental monitoring, food analyses, and clinical diagnoses, respectively. More meaningfully, the generated substrate sensing mode is successfully applied to construct a cascade reaction coupling ratiometric fluorescent immunoassay for the detection of clenbuterol, increasing 15-fold in detection sensitivity compared with the traditional enzyme-linked immunosorbent assay. It is expected that the expanded universal substrate sensing modes and the Schiff-base chemistry-enhanced nanozyme can enlighten the exploration of innovative biosensors.


Asunto(s)
Técnicas Biosensibles , Catecol Oxidasa , Ensayo de Inmunoadsorción Enzimática
20.
Food Res Int ; 163: 112293, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36596197

RESUMEN

Nature-derived chemicals have recently gained increased attention to settle down the challenges in the food industry. Quercetin has long been used as a natural medicine but its photoactivity has been neglected. In this work, by combining photodynamic bacteria inactivation (PDI) with an edible coating (Pectin/Quercetin) derived from FDA-approved chemicals, extend shelf-life and protected commercial quality of fresh-cut apples were achieved. Firstly, the potential photoactivated antibacterial performance of Quercetin (a natural plant flavonoid) was clarified with the treatment of a simulated sunlight lamp, realizing antibacterial efficacy of 100 % towards S. aureus (50 min) and L. monocytogenes (80 min) with light treatment. To develop safe and effective preservation of fresh-cut apples, Pectin/Quercetin edible coatings with 100 µmol/L quercetin were adopted. The results showed that the prepared edible coatings form a protective barrier over the surface of apples, effectively resisting bacterial infection and extending shelf life to 10 days while maintaining good commercial quality (including preferable color, keeping 100 % hardness, 80 % sugar content and 17.3 % weightlessness rate). Therefore, the prepared light-driven Pectin/Quercetin in this work has the potential to develop as fresh-cut fruit preservation technology.


Asunto(s)
Películas Comestibles , Malus , Malus/microbiología , Conservación de Alimentos/métodos , Quercetina/farmacología , Staphylococcus aureus , Fitoquímicos , Pectinas , Antibacterianos
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