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1.
Phytochem Anal ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39311001

RESUMEN

INTRODUCTION: Polygalae Radix (PR) is known to relieve toxicity and increase efficiency in various diseases after processing. However, there were few studies for aromatic carboxylic acids (ACAs) due to the limited detection, especially for the metabolites within m/z 100-2000. OBJECTIVES: This study aims to elucidate the whole metabolism of PR with/without licorice (LP), focusing on metabolites within m/z 100-2000 and pharmacodynamics in vivo. MATERIAL AND METHODS: This study was established by the combination of multidimensional ultra-high performance liquid chromatography coupled with a mass spectrometer (UPLC-MS) technology with protein sedimentation method to analyze metabolites in plasma, brain, colon, and stomach contents. Quantitative monitoring ACAs was enhanced with our novel stable isotope derivatization (SILD) technique. And then the pharmacokinetics (PK) study of relatively large metabolites was carried out. A targeted network pharmacology approach was established to avoid false positive results, mapping interactions relevant to Alzheimer's disease (AD), and other conditions. RESULTS: The 85 polygala metabolites were qualitatively analyzed in plasma, brain, colon, and stomach contents. The 11 types of relatively large metabolites and 8 types of ACAs were quantitatively monitored. Among them, nine types of relatively large metabolites were assessed through PK studies. In targeted network pharmacology, it highlighted the significance of small molecular metabolites, including ACAs et al, which were frequently overlooked. LP may play a more key role mainly through neural active ligand-receptor interaction, AD, and pertussis pathways. These findings have outlined a step-by-step strategy for in-depth research in vivo, laying a foundation for further verification of biological function.

2.
BMC Womens Health ; 24(1): 491, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237940

RESUMEN

OBJECTIVE: The aim of this study is to assess the use of machine learning methodologies in the diagnosis of endometriosis (EM). METHODS: This study included a total of 106 patients with EM and 203 patients with non-EM conditions (like simple cysts and simple uterine fibroids), all admitted to the Shunyi Women's and Children's Hospital of Beijing Children's Hospital between January 2017 and September 2022. All participants were free of comorbidities and their diagnoses were confirmed via postoperative pathology. Comparative analysis was conducted between the EM and non-EM groups. Baseline data were assessed, including white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, mean platelet volume, hemoglobin, carbohydrate antigen 125 (CA125), carbohydrate antigen 199, coagulation parameters, and other serologic indicators. An optimal predictive model was developed using an artificial intelligence algorithm to determine the presence of EM. The objective is to provide new insights for the clinical diagnosis and treatment of EM. RESULTS: The random forest algorithm demonstrated superior performance when compared to decision trees, LogitBoost, artificial neural networks, naïve Bayes, support vector machines, and linear regression in machine learning methods. Combining CA125 with the NLR yielded a better prediction of EM than using CA125 alone when applying the random forest algorithm. The accuracy of predicting EM with CA125 combined with NLR was 78.16%, with a sensitivity of 86.21% and an area under the curve (AUC) of 0.85 (P < 0.05). In contrast, using CA125 alone resulted in an EM prediction accuracy of 75.8%, with a sensitivity of 79.3% and an AUC of 0.82 (P < 0.05). CONCLUSION: The diagnostic value of serum CA125 combined with the NLR for EM is higher than that of serum CA125 alone. This finding indicates that NLR could serve as a new supplementary biomarker along with serum CA125 in the diagnosis of EM.


Asunto(s)
Antígeno Ca-125 , Endometriosis , Aprendizaje Automático , Humanos , Femenino , Endometriosis/diagnóstico , Endometriosis/sangre , Antígeno Ca-125/sangre , Adulto , Neutrófilos , Algoritmos
3.
Microorganisms ; 12(8)2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39203522

RESUMEN

Understanding the roles of core bacterial taxa in forage production is crucial for developing sustainable fertilization practices that enhance the soil bacteria and forage yield. This study aims to investigate the impact of different fertilization regimes on soil bacterial community structure and function, with a particular focus on the role of core bacterial taxa in contributing to soil nutrient content and enhancing forage yield. Field experiments and high-throughput sequencing techniques were used to analyze the soil bacterial community structure and function under various fertilization regimes, including six treatments, control with no amendment (CK), double the standard rate of organic manure (T01), the standard rate of organic manure with nitrogen input equal to T04 (T02), half the standard rate of inorganic fertilizer plus half the standard rate of organic manure (T03), the standard rate of inorganic fertilizer reflecting local practice (T04), and double the standard rate of inorganic fertilizer (T05). The results demonstrated that organic manure treatments, particularly T01, significantly increased the forage yield and the diversity of core bacterial taxa. Core taxa from the Actinomycetota, Alphaproteobacteria, and Gammaproteobacteria classes were crucial in enhancing the soil nutrient content, directly correlating with forage yield. Fertilization significantly influenced functions relating to carbon and nitrogen cycling, with core taxa playing central roles. The diversity of core microbiota and soil nutrient levels were key determinants of forage yield variations across treatments. These findings underscore the critical role of core bacterial taxa in agroecosystem productivity and advocate for their consideration in fertilization strategies to optimize forage yield, supporting the shift towards sustainable agricultural practices.

5.
J Colloid Interface Sci ; 677(Pt A): 1029-1036, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39134077

RESUMEN

Aqueous zinc ion batteries (AZIBs) have attracted much attention for their safety, low cost and high theoretical capacity. Nevertheless, Zn dendrites and the adverse reactions such as corrosion, hydrogen evolution and passivation on the anode affect the cycle life and stability of AZIBs. Herein, superabsorbent starch (SS) was employed on Zn foil to form an artificial interface protection layer, which inhibited the formation of dendrites by guiding the uniform deposition of Zn2+. SS with a large amount of oxygen-containing functional group is superabsorbent, which can attract the active water around the hydrated Zn2+, promoting the desolvation process of the hydrated Zn2+ and significantly inhibiting the occurrence of hydrogen evolution reaction. In addition, the inherent pore structure of the SS artificial interfacial layer can induce uniform nucleation of Zn2+ and inhibit the dendrites growth. Moreover, compared to bare Zn//MnO2 cell (44.1 %), the capacity retention of Zn@SS//MnO2 cell remained as high as 87.8 % after 1000 cycles at 1.5 A g-1. The simple method provided a new method for the rapid development of AZIBs.

6.
J Vet Med Sci ; 86(9): 1008-1015, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39069485

RESUMEN

The prevalence of chicken coccidiosis in the poultry industry is a significant concern, further exacerbated by the emergence of drug-resistant coccidia resulting from the indiscriminate use of medications. Ethanamizuril, a novel triazine anti-coccidial compound, has been used to combat drug resistance. Currently, it is known that Ethanamizuril acts on the second-generation merozoites and early gametogenesis stages of Eimeria. Limited information exists regarding its impact on the early merozoites and exogenous stage of Eimeria. In the present study, the anti-coccidial properties of Ethanamizuril were evaluated both in vitro and in vivo. The in vitro experiments demonstrated that Ethanamizuril effectively inhibits the sporulation of E. tenella oocysts in a dose-dependent manner and significantly reduces the sporozoite excystation rate. Furthermore, in vivo tests revealed that treatment with 10 mg/L Ethanamizuril in drinking water significantly decreased the copy number of first-generation and secondary-generation merozoites in the chicken cecum, indicating that it can inhibit the development of whole schizonts development. Moreover, treatment with Ethanamizuril demonstrated excellent protective efficacy with an anti-coccidial index (ACI) of 180.2, which was manifested through higher body weight gains, lighter cecal lesion, lower fecal oocyst shedding score and reduced liver index. Collectively, this study suggests that Ethanamizuril effectively treats E. tenella infection by inhibiting both endogenous and exogenous stages development.


Asunto(s)
Pollos , Coccidiosis , Coccidiostáticos , Eimeria tenella , Enfermedades de las Aves de Corral , Triazinas , Animales , Triazinas/farmacología , Coccidiostáticos/farmacología , Coccidiostáticos/uso terapéutico , Eimeria tenella/efectos de los fármacos , Coccidiosis/tratamiento farmacológico , Coccidiosis/veterinaria , Coccidiosis/parasitología , Pollos/parasitología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/parasitología , Oocistos/efectos de los fármacos
7.
Acta Pharm Sin B ; 14(7): 3049-3067, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39027246

RESUMEN

The mucosal barrier is crucial for intestinal homeostasis, and goblet cells are essential for maintaining the mucosal barrier integrity. The proviral integration site for Moloney murine leukemia virus-1 (PIM1) kinase regulates multiple cellular functions, but its role in intestinal homeostasis during colitis is unknown. Here, we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models, in the presence of intestinal microbiota. Epithelial PIM1 leads to decreased goblet cells, thus impairing resistance to colitis and colitis-associated colorectal cancer (CAC) in mice. Mechanistically, PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling pathways. Interestingly, PIM1 interacts with histone deacetylase 2 (HDAC2) and downregulates its level via phosphorylation, thereby altering the epigenetic profiles of Wnt signaling pathway genes. Collectively, these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis, which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

8.
BMJ Open Respir Res ; 11(1)2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39032939

RESUMEN

BACKGROUND: Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China. METHODS: We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency. RESULTS: The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below -950 Hounsfield units, logLAA-950: 0.19±0.65 vs -0.28±0.63, p<0.001) and air trapping (logLAA-856: 1.03±0.65 vs 0.68±0.70, p<0.001) than those with normal ventilatory efficiency. Older age (60-69 years, OR 3.10 (95% CI 1.33 to 7.21), p=0.009 and 70-80 years, OR 6.48 (95% CI 2.56 to 16.43), p<0.001 vs 40-49 years) and smoking (former, OR 3.19 (95% CI 1.29 to 7.86), p=0.012; current, OR 4.27 (95% CI 1.78 to 10.24), p=0.001 vs never) were identified as high risk factors of impaired ventilatory efficiency. CONCLUSIONS: Impaired ventilatory efficiency was associated with poorer respiratory characteristics. Longitudinal studies are warranted to explore the progression of individuals with impaired ventilatory efficiency.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Humanos , China/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Anciano , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Espirometría , Prueba de Esfuerzo , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Tolerancia al Ejercicio , Factores de Riesgo , Ventilación Pulmonar
9.
Nanoscale ; 16(23): 11250-11261, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38780439

RESUMEN

High-efficiency water electrolysis over a broad pH range is desirable but challenging. Herein, Ru-decorated VS2 on carbon cloth (Ru-VS2/CC) has been in situ synthesized, which features the regulated electronic structure of VS2 by introducing Ru. It is remarkable that the optimal Ru-VS2/CC displays excellent electrocatalytic hydrogen evolution activity with overpotentials of 89 and 87 mV at -10 mA cm-2 in 0.5 M H2SO4 and 1.0 M KOH, respectively. Theoretical calculations and electrocatalytic measurements have demonstrated that introducing Ru induces an enhanced charge density around the Fermi level, facilitating charge transfer and speeding up the electrocatalytic HER kinetics. The Gibbs free energy of the hydrogen intermediate (ΔGH*) of Ru-VS2/CC (0.23 eV) is much closer to zero than that of pure VS2 (0.51 eV) and Ru (-0.37 eV), demonstrating an easier hydrogen adsorption and desorption process for Ru-VS2/CC. The more favorable ΔGH*, differential charge density and the d-band center endow Ru-VS2 with enhanced intrinsic electrocatalytic activity. This study presents a feasible strategy for enhancing electrocatalytic HER activity by the regulation of the electronic structure and the rational integration of dual active components.

10.
Microorganisms ; 12(5)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38792680

RESUMEN

Cysticercus pisiformis is a kind of tapeworm larvae of Taenia pisiformis, which parasitizes the liver envelope, omentum, mesentery, and rectum of rodents such as rabbits. Cysteine protease inhibitors derived from helminth were immunoregulatory molecules of intermediate hosts and had an immunomodulatory function that regulates the production of inflammatory factors. Thus, in the present research, the recombinant Stefin of C. pisiformis was confirmed to have the potential to fight inflammation in LPS-Mediated RAW264.7 murine macrophages. CCK8 test showed that rCpStefin below 50 µg/mL concentration did not affect cellular viability. Moreover, the NO production level determined by the Griess test was decreased. In addition, the secretion levels of IL-1ß, IL-6, and TNF-α as measured by ELISA were decreased. Furthermore, it exerted anti-inflammatory activity by decreasing the production of proinflammatory cytokines and proinflammatory mediators, including IL-1ß, IL-6, TNF-α, iNOS, and COX-2 at the gene transcription level, as measured by qRT-PCR. Therefore, Type I cystatin derived from C. pisiformis suppresses the LPS-Mediated inflammatory response of the intermediate host and is a potential candidate for the treatment of inflammatory diseases.

11.
BMJ Open Respir Res ; 11(1)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789282

RESUMEN

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Espirometría , Humanos , Masculino , Femenino , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Persona de Mediana Edad , China/epidemiología , Anciano , Volumen Espiratorio Forzado , Capacidad Vital , Fumar/epidemiología , Fumar/efectos adversos , Pulmón/fisiopatología , Pronóstico
12.
Arch Bronconeumol ; 60(7): 402-409, 2024 Jul.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38749856

RESUMEN

BACKGROUND: High blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community. METHODS: We obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/µL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma. RESULTS: Of the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09-1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results. CONCLUSIONS: COPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC.


Asunto(s)
Eosinófilos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Masculino , Femenino , Estudios Prospectivos , China/epidemiología , Anciano , Persona de Mediana Edad , Recuento de Leucocitos , Volumen Espiratorio Forzado , Estudios de Seguimiento , Progresión de la Enfermedad
13.
Chem Commun (Camb) ; 60(36): 4745-4764, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38647208

RESUMEN

Mycotoxin contamination in food products may cause serious health hazards and economic losses. The effective control and accurate detection of mycotoxins have become a global concern. Even though a variety of methods have been developed for mycotoxin detection, most conventional methods suffer from complicated operation procedures, low sensitivity, high cost, and long assay time. Therefore, the development of simple and sensitive methods for mycotoxin assay is highly needed. The introduction of nucleic acid signal amplification technology (NASAT) into aptasensors significantly improves the sensitivity and facilitates the detection of mycotoxins. Herein, we give a comprehensive review of the recent advances in NASAT-based aptasensors for assaying mycotoxins and summarize the principles, features, and applications of NASAT-based aptasensors. Moreover, we highlight the challenges and prospects in the field, including the simultaneous detection of multiple mycotoxins and the development of portable devices for field detection.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Micotoxinas , Técnicas de Amplificación de Ácido Nucleico , Micotoxinas/análisis , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Contaminación de Alimentos/análisis , Ácidos Nucleicos/análisis
14.
Adv Mater ; 36(24): e2313152, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38491731

RESUMEN

Zinc-based batteries (ZBBs) have demonstrated considerable potential among secondary batteries, attributing to their advantages including good safety, environmental friendliness, and high energy density. However, ZBBs still suffer from issues such as the formation of zinc dendrites, occurrence of side reactions, retardation of reaction kinetics, and shuttle effects, posing a great challenge for practical applications. As promising porous materials, covalent organic frameworks (COFs) and their derivatives have rigid skeletons, ordered structures, and permanent porosity, which endow them with great potential for application in ZBBs. This review, therefore, provides a systematic overview detailing on COFs structure pertaining to electrochemical performance of ZBBs, following an in depth discussion of the challenges faced by ZBBs, which includes dendrites and side reactions at the anode, as well as dissolution, structural change, slow kinetics, and shuttle effect at the cathode. Then, the structural advantages of COF-correlated materials and their roles in various ZBBs are highlighted. Finally, the challenges of COF-correlated materials in ZBBs are outlined and an outlook on the future development of COF-correlated materials for ZBBs is provided. The review would serve as a valuable reference for further research into the utilization of COF-correlated materials in ZBBs.

15.
Respir Res ; 25(1): 149, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555433

RESUMEN

BACKGROUND: The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR. METHODS: Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model. RESULTS: This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up. CONCLUSIONS: The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.


Asunto(s)
Asma , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Asma/diagnóstico , Broncodilatadores/uso terapéutico , Volumen Espiratorio Forzado , Oscilometría , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Pruebas de Función Respiratoria , Espirometría
16.
Biochim Biophys Acta Rev Cancer ; 1879(3): 189096, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38499079

RESUMEN

Colorectal cancer (CRC) is one of the deadliest malignancies worldwide, ranking third in incidence and second in mortality. Remarkably, early stage localized CRC has a 5-year survival rate of over 90%; in stark contrast, the corresponding 5-year survival rate for metastatic CRC (mCRC) is only 14%. Compounding this problem is the staggering lack of effective therapeutic strategies. Beyond genetic mutations, which have been identified as critical instigators of CRC initiation and progression, the importance of epigenetic modifications, particularly DNA methylation (DNAm), cannot be underestimated, given that DNAm can be used for diagnosis, treatment monitoring and prognostic evaluation. This review addresses the intricate mechanisms governing aberrant DNAm in CRC and its profound impact on critical oncogenic pathways. In addition, a comprehensive review of the various techniques used to detect DNAm alterations in CRC is provided, along with an exploration of the clinical utility of cancer-specific DNAm alterations.


Asunto(s)
Neoplasias Colorrectales , Metilación de ADN , Epigénesis Genética , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/diagnóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Relevancia Clínica
17.
Anal Chem ; 96(13): 5323-5330, 2024 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-38501982

RESUMEN

Oxidative DNA damage is closely associated with the occurrence of numerous human diseases and cancers. 8-Oxo-7,8-dihydroguanine (8-oxoG) is the most prevalent form of DNA damage, and it has become not only an oxidative stress biomarker but also a new epigenetic-like biomarker. However, few approaches are available for the locus-specific detection of 8-oxoG because of the low abundance of 8-oxoG damage in DNA and the limited sensitivity of existing assays. Herein, we demonstrate the elongation and ligation-mediated differential coding for label-free and locus-specific analysis of 8-oxoG in DNA. This assay is very simple without the involvement of any specific labeled probes, complicated steps, and large sample consumption. The utilization of Bsu DNA polymerase can specifically initiate a single-base extension reaction to incorporate dATP into the opposite position of 8-oxoG, endowing this assay with excellent selectivity. The introduction of cascade amplification reaction significantly enhances the sensitivity. The proposed method can monitor 8-oxoG with a limit of detection of 8.21 × 10-19 M (0.82 aM), and it can identify as low as 0.001% 8-oxoG damage from a complex mixture with excessive undamaged DNAs. This method can be further applied to measure 8-oxoG levels in the genomic DNA of human cells under diverse oxidative stress, holding prospect potential in the dynamic monitoring of critical 8-oxoG sites, early clinical diagnosis, and gene damage-related biomedical research.


Asunto(s)
ADN Polimerasa Dirigida por ADN , ADN , Guanina/análogos & derivados , Humanos , ADN/genética , ADN Polimerasa Dirigida por ADN/metabolismo , Daño del ADN , Biomarcadores , Reparación del ADN
18.
Chem Commun (Camb) ; 60(22): 3075-3078, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38404229

RESUMEN

We construct a simple fluorescent biosensor for single-molecule counting of flap endonuclease 1 (FEN1) based on ligase detection reaction (LDR) amplification-activated CRISPR-Cas12a. This biosensor exhibits excellent selectivity and high sensitivity with a detection limit (LOD) of 1.31 × 10-8 U. Moreover, it can be employed to screen the FEN1 inhibitors and quantitatively measure the FEN1 activity in human cells and breast cancer tissues, holding great promise in clinical diagnosis and drug discovery.


Asunto(s)
Técnicas Biosensibles , Neoplasias , Humanos , Endonucleasas de ADN Solapado , Sistemas CRISPR-Cas/genética , Colorantes , Descubrimiento de Drogas
19.
Talanta ; 272: 125784, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38364555

RESUMEN

Fat mass and obesity-associated protein (FTO) is a crucial eraser of RNA N6- methyladenosine (m6A) modification, and abnormal FTO expression level is implicated in pathogenesis of numerous cancers. Herein, we demonstrate the construction of a label-free fluorescent biosensor for homogeneous detection of m6A eraser FTO in breast cancer tissues. When FTO is present, it specifically erases the methyl group in m6A, inducing the cleavage of demethylated DNA by endonuclease DpnII and the generation of a single-stranded DNA (ssDNA) with a 3'-hydroxyl group. Subsequently, terminal deoxynucleotidyl transferase (TdT) promotes the incorporation of dTTPs into the ssDNA to obtain a long polythymidine (T) DNA sequence. The resultant long poly (T) DNA sequence can act as a template to trigger hyperbranched strand displacement amplification (HSDA), yielding numerous DNA fragments that may be stained by SYBR Gold to produce an enhanced fluorescence signal. This biosensor processes ultrahigh sensitivity with a detection limit of 1.65 × 10-10 mg/mL (2.6 fM), and it can detect the FTO activity in a single MCF-7 cell. Moreover, this biosensor can screen the FTO inhibitors, evaluate enzyme kinetic parameters, and discriminate the FTO expression levels in the tissues of breast cancer patients and healthy persons.


Asunto(s)
Técnicas Biosensibles , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , ADN , ADN de Cadena Simple/genética , ARN , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética
20.
Nanoscale ; 16(3): 1406-1414, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38165953

RESUMEN

Itinerant ferromagnetism at room temperature is a key factor for spin transport and manipulation. Here, we report the realization of near-room temperature itinerant ferromagnetism in Co doped Fe5GeTe2 thin flakes. The ferromagnetic transition temperature TC (∼323 K-337 K) is almost unchanged when the thickness is as low as 12 nm and is still about 284 K at 2 nm (bilayer thickness). Theoretical calculations further indicate that the ferromagnetism persists in monolayer Fe4CoGeTe2. In addition to the robust ferromagnetism down to the ultrathin limit, Fe4CoGeTe2 exhibits an unusual temperature- and thickness-dependent intrinsic anomalous Hall effect. We propose that it could be ascribed to the dependence of the band structure on thickness that changes the Berry curvature near the Fermi energy level subtly. The near-room temperature ferromagnetism and tunable anomalous Hall effect in atomically thin Fe4CoGeTe2 provide opportunities to understand the exotic transport properties of two-dimensional van der Waals magnetic materials and explore their potential applications in spintronics.

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