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1.
Cancer Cell Int ; 24(1): 53, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310291

RESUMEN

Ovarian cancer (OV) is the most lethal gynecological malignancy worldwide, with high recurrence rates. Anoikis, a newly-acknowledged form of programmed cell death, plays an essential role in cancer progression, though studies focused on prognostic patterns of anoikis in OV are still lacking. We filtered 32 potential anoikis-related genes (ARGs) among the 6406 differentially expressed genes (DEGs) between the 180 normal controls and 376 TCGA-OV samples. Through the LASSO-Cox analysis, a 2-gene prognostic signature, namely AKT2, and DAPK1, was finally distinguished. We then demonstrated the promising prognostic value of the signature through the K-M survival analysis and time-dependent ROC curves (p-value < 0.05). Moreover, based on the signature and clinical features, we constructed and validated a nomogram model for 1-year, 3-year, and 5-year overall survival, with reliable prognostic values in both TCGA-OV training cohort (p-value < 0.001) and ICGC-OV validation cohort (p-value = 0.030). We evaluated the tumor immune landscape through the CIBERSORT algorithm, which indicated the upregulation of resting Myeloid Dendritic Cells (DCs), memory B cells, and naïve B cells and high expression of key immune checkpoint molecules (CD274 and PDCD1LG2) in the high-risk group. Interestingly, the high-risk group exhibited better sensitivity toward immunotherapy and less sensitivity toward chemotherapies, including Cisplatin and Bleomycin. Especially, based on the IHC of tissue microarrays among 125 OV patients at our institution, we reported that aberrant upregulation of DAPK1 was related to poor prognosis. Conclusively, the anoikis-related signature was a promising tool to evaluate prognosis and predict therapy responses, thus assisting decision-making in the realm of OV precision medicine.

2.
BMC Cancer ; 24(1): 267, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38408960

RESUMEN

PURPOSE: Significant advancements in improving ovarian cancer (OC) outcomes have been limited over the past decade. To predict prognosis and improve outcomes of OC, we plan to develop and validate a robust prognosis signature based on blood features. METHODS: We screened age and 33 blood features from 331 OC patients. Using ten machine learning algorithms, 88 combinations were generated, from which one was selected to construct a blood risk score (BRS) according to the highest C-index in the test dataset. RESULTS: Stepcox (both) and Enet (alpha = 0.7) performed the best in the test dataset with a C-index of 0.711. Meanwhile, the low RBS group possessed observably prolonged survival in this model. Compared to traditional prognostic-related features such as age, stage, grade, and CA125, our combined model had the highest AUC values at 3, 5, and 7 years. According to the results of the model, BRS can provide accurate predictions of OC prognosis. BRS was also capable of identifying various prognostic stratifications in different stages and grades. Importantly, developing the nomogram may improve performance by combining BRS and stage. CONCLUSION: This study provides a valuable combined machine-learning model that can be used for predicting the individualized prognosis of OC patients.


Asunto(s)
Nomogramas , Neoplasias Ováricas , Humanos , Femenino , Adulto , Pronóstico , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/cirugía , Algoritmos , Aprendizaje Automático
3.
Environ Sci Technol ; 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38261755

RESUMEN

Air pollution poses a critical public health threat around many megacities but in an uneven manner. Conventional models are limited to depict the highly spatial- and time-varying patterns of ambient pollutant exposures at the community scale for megacities. Here, we developed a machine-learning approach that leverages the dynamic traffic profiles to continuously estimate community-level year-long air pollutant concentrations in Los Angeles, U.S. We found the introduction of real-world dynamic traffic data significantly improved the spatial fidelity of nitrogen dioxide (NO2), maximum daily 8-h average ozone (MDA8 O3), and fine particulate matter (PM2.5) simulations by 47%, 4%, and 15%, respectively. We successfully captured PM2.5 levels exceeding limits due to heavy traffic activities and providing an "out-of-limit map" tool to identify exposure disparities within highly polluted communities. In contrast, the model without real-world dynamic traffic data lacks the ability to capture the traffic-induced exposure disparities and significantly underestimate residents' exposure to PM2.5. The underestimations are more severe for disadvantaged communities such as black and low-income groups, showing the significance of incorporating real-time traffic data in exposure disparity assessment.

4.
Proc Natl Acad Sci U S A ; 118(26)2021 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-34155113

RESUMEN

The large fluctuations in traffic during the COVID-19 pandemic provide an unparalleled opportunity to assess vehicle emission control efficacy. Here we develop a random-forest regression model, based on the large volume of real-time observational data during COVID-19, to predict surface-level NO2, O3, and fine particle concentration in the Los Angeles megacity. Our model exhibits high fidelity in reproducing pollutant concentrations in the Los Angeles Basin and identifies major factors controlling each species. During the strictest lockdown period, traffic reduction led to decreases in NO2 and particulate matter with aerodynamic diameters <2.5 µm by -30.1% and -17.5%, respectively, but a 5.7% increase in O3 Heavy-duty truck emissions contribute primarily to these variations. Future traffic-emission controls are estimated to impose similar effects as observed during the COVID-19 lockdown, but with smaller magnitude. Vehicular electrification will achieve further alleviation of NO2 levels.


Asunto(s)
Contaminación del Aire/análisis , COVID-19/epidemiología , Aprendizaje Automático , Modelos Teóricos , Transportes , Contaminantes Atmosféricos/análisis , Algoritmos , Electricidad , Humanos , Material Particulado/análisis , Emisiones de Vehículos
5.
Int J Mol Sci ; 25(2)2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38255916

RESUMEN

Chicoric acid (CA) has been reported to exhibit biological activities; it remains unclear, however, whether CA could regulate colitis via modulation of the gut microbiota and metabolites. This study aimed to assess CA's impact on dextran sulfate sodium (DSS)-induced colitis, the gut microbiota, and metabolites. Mice were induced with 2.5% DSS to develop colitis over a 7-day period. CA was administered intragastrically one week prior to DSS treatment and continued for 14 days. The microbial composition in the stool was determined using 16S rRNA sequencing, while non-targeted metabolomics was employed to analyze the metabolic profiles of each mouse group. The results show that CA effectively alleviated colitis, as evidenced by an increased colon length, lowered disease activity index (DAI) and histological scores, and decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. CA intervention restored the structure of gut microbiota. Specifically, it decreased the abundance of Bacteroidetes and Cyanobacteria at the phylum level and Bacteroides, Rosiarcus, and unclassified Xanthobacteraceae at the genus level, and increased the abundance of unclassified Lachnospiraceae at the genus level. Metabolomic analysis revealed that CA supplementation reversed the up-regulation of asymmetric dimethylarginine, N-glycolylneuraminic acid, and N-acetylneuraminic acid, as well as the down-regulation of phloroglucinol, thiamine, 4-methyl-5-thiazoleethanol, lithocholic acid, and oxymatrine induced by DSS. Our current research provides scientific evidence for developing CA into an anti-colitis functional food ingredient. Further clinical trials are warranted to elucidate the efficacy and mechanism of CA in treating human inflammatory bowel disease (IBD).


Asunto(s)
Ácidos Cafeicos , Colitis , Microbioma Gastrointestinal , Succinatos , Humanos , Animales , Ratones , Ratones Endogámicos BALB C , Sulfato de Dextran/toxicidad , ARN Ribosómico 16S/genética , Colitis/inducido químicamente , Colitis/tratamiento farmacológico
6.
Cancer Cell Int ; 23(1): 232, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37803446

RESUMEN

Ovarian cancer (OV) is the most lethal gynecological malignancies worldwide. The coagulation cascade could induce tumor cell infiltration and contribute to OV progression. However, coagulation-related gene (CRG) signature for OV prognosis hasn't been determined yet. In this study, we evaluated the prognostic value of coagulation scores through receiver operating characteristics (ROC) analysis and K-M curves, among OV patients at our institution. Based on the transcriptome data of TCGA-OV cohort, we stratified two coagulation-related subtypes with distinct differences in prognosis and tumor immune microenvironment (p < 0.05). Moreover, from the 6406 differentially-expressed genes (DEGs) between the GTEx (n = 180) and TCGA-OV cohorts (n = 376), we identified 138 potential CRGs. Through LASSO-Cox algorithm, we finally distinguished a 3-gene signature (SERPINA10, CD38, and ZBTB16), with promising prognostic ability in both TCGA (p < 0.001) and ICGC cohorts (p = 0.040). Stepwise, we constructed a nomogram based on the clinical features and coagulation-related signature for overall survival prediction, with the C-index of 0.6761, which was evaluated by calibration curves. Especially, based on tissue microarrays analysis, Quantitative real-time fluorescence PCR (qRT-PCR), and Western Blot, we found that aberrant upregulation of CRGs was related to poor prognosis in OV at both mRNA and protein level (p < 0.05). Collectively, the coagulation-related signature was a robust prognostic biomarker, which could provide therapeutic benefits for chemotherapy/immunotherapy and assist clinical decision in OV patients.

7.
Crit Rev Food Sci Nutr ; : 1-14, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37287270

RESUMEN

Osmanthus fragrans (O. fragrans) has been cultivated in China for over 2,500 years as a traditional fragrant plant. Recently, O. fragrans has drawn increasing attention due to its unique aroma and potential health benefits. In this review, the aroma and functional components of O. fragrans are summarized, and their biosynthetic mechanism is discussed. The beneficial functions and related molecular mechanism of O. fragrans extract are then highlighted. Finally, potential applications of O. fragrans are summarized, and future perspectives are proposed and discussed. According to the current research, O. fragrans extracts and components have great potential to be developed into value-added functional ingredients with preventive effects on certain chronic diseases. However, it is crucial to develop efficient, large-scale, and commercially viable extraction methods to obtain the bioactive components from O. fragrans. Furthermore, more clinical studies are highly needed to explore the beneficial functions of O. fragrans and guide its development into functional food products.

8.
Genomics ; 114(5): 110445, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35934260

RESUMEN

Centromere proteins (CENPs) are nuclear proteins that are involved in centromere formation and chromosome segregation during mitosis. Some members of CENPs have been extensively studied in the initiation and development of cancers. However, the expression patterns and exact roles of CENPs in ovarian cancer (OC) have not been fully elucidated. In this study, we comprehensively assessed the genetic variation, expression patterns and prognostic value of CENPs in OC by several databases. The mRNA expression levels of CENPA/F/H/L/N/U/W were found to be significantly upregulated in OC and related to worse prognosis. Additionally, function enrichment analysis showed that CENPs were involved in DNA repair and cell division. Meanwhile, immune infiltration analysis elucidated that CENPs were associated with myeloid-derived suppressor cells (MDSCs) and major histocompatibility complex (MHC). These results suggested that CENPs might serve as potential diagnostic and prognostic markers and provide new insights for the development of CENPs-targeted therapeutics for ovarian cancer.


Asunto(s)
Centrómero , Neoplasias Ováricas , Carcinoma Epitelial de Ovario/genética , Femenino , Humanos , Proteínas Nucleares/genética , Neoplasias Ováricas/genética , Pronóstico , ARN Mensajero/metabolismo
9.
Plant Physiol ; 187(3): 1202-1220, 2021 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33871654

RESUMEN

Inflorescence architecture in cereal crops directly impacts yield potential through regulation of seed number and harvesting ability. Extensive architectural diversity found in inflorescences of grass species is due to spatial and temporal activity and determinacy of meristems, which control the number and arrangement of branches and flowers, and underlie plasticity. Timing of the floral transition is also intimately associated with inflorescence development and architecture, yet little is known about the intersecting pathways and how they are rewired during development. Here, we show that a single mutation in a gene encoding an AP1/FUL-like MADS-box transcription factor significantly delays flowering time and disrupts multiple levels of meristem determinacy in panicles of the C4 model panicoid grass, Setaria viridis. Previous reports of AP1/FUL-like genes in cereals have revealed extensive functional redundancy, and in panicoid grasses, no associated inflorescence phenotypes have been described. In S. viridis, perturbation of SvFul2, both through chemical mutagenesis and gene editing, converted a normally determinate inflorescence habit to an indeterminate one, and also repressed determinacy in axillary branch and floral meristems. Our analysis of gene networks connected to disruption of SvFul2 identified regulatory hubs at the intersection of floral transition and inflorescence determinacy, providing insights into the optimization of cereal crop architecture.


Asunto(s)
Redes Reguladoras de Genes , Setaria (Planta)/genética , Factores de Transcripción/metabolismo , Flores/genética , Flores/fisiología , Inflorescencia/genética , Inflorescencia/fisiología , Meristema/genética , Meristema/fisiología , Mutación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Setaria (Planta)/fisiología , Factores de Tiempo , Factores de Transcripción/genética
10.
Nutr Cancer ; 74(3): 796-805, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34060392

RESUMEN

Existing evidence suggests diet and chronic inflammation as risk factors in ovarian cancer (OC) development. We aim to conduct a meta-analysis exploring possible associations between dietary inflammatory potential and OC. A systematic search was conducted through PubMed, Scopus, Embase, and PMC databases for studies reporting relationships between dietary inflammatory potential and OC risk published up to September 2020. We included six studies for stepwise analysis, of which 5,468 among 197,086 individuals developed OC. Pooled odds ratios (ORs) were calculated by fixed-effects models, while heterogeneity was assessed by Q test and I2 statistic. The results revealed a positive association between dietary inflammatory potential measured by the Dietary Inflammatory Index (DII) and OC(P < 0.05). Individuals with higher DII scores had a 42% increased risk of OC incidence [OR = 1.42, 95% confidence interval (CI): 1.19-1.65]. The analysis considering DII as a continuous variable showed an increased risk of 10% for 1-point increase of DII(OR = 1.10, 95% CI: 1.06-1.14). Subgroup analysis revealed that increased risk of OC in individuals with higher DII scores vs. those with lower DII was only significant among post-menopausal women(OR = 1.72, 95% CI: 1.26-2.21) rather than those pre/peri-menopausal(OR = 1.21, 95% CI: 0.63-1.79). Pro-inflammatory diets with higher DII score were significantly related to increased OC risk among post-menopausal women.


Asunto(s)
Dieta , Neoplasias Ováricas , Carcinoma Epitelial de Ovario/complicaciones , Dieta/efectos adversos , Femenino , Humanos , Inflamación/etiología , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/etiología , Factores de Riesgo
11.
BMC Public Health ; 22(1): 620, 2022 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-35354440

RESUMEN

BACKGROUND: Health belief is an important factor affecting lung cancer screening in high-risk population, but the research based on Chinese cultural background is still insufficient. Therefore, we adapted the English version of the Lung Cancer Screening Health Belief Scales (LCSHB) into the Chinese version (LCSHB-C) and examined its psychometric characteristics. METHODS: After obtaining authorization from the original author, the LCSHB-C was adapted based upon Brislin's translation model. Using a variety of community-based recruitment methods, a total of 353 participants were recruited in Fuzhou, Fujian province, China to complete the questionnaires. We combined the classical test theory and item response theory to examine the psychometric properties of the LCSHB-C. RESULTS: The Cronbach's alpha for the four subscales ranged from 0.83 ~ 0.93. The content validity index for the four subscales was ranged from 0.87 ~ 1.0. Confirmatory factor analysis supported each subscale structure model fit well. Rasch analysis results further validated the reliability and validity of the four subscales. The person reliability and separation index of each subscale ranged from 0.77 to 0.87 and 1.83 to 2.63, respectively. CONCLUSIONS: The LCSHB-C is a reliable and valid instrument used to measure health beliefs related to lung cancer screening among those high-risk for lung cancer in China, which facilitates the development of lung cancer screening programs and promotes the "three early prevention strategies" of lung cancer (i.e.,early detection, early diagnosis and early treatment).


Asunto(s)
Detección Precoz del Cáncer , Neoplasias Pulmonares , Adaptación Fisiológica , Humanos , Neoplasias Pulmonares/diagnóstico , Reproducibilidad de los Resultados , Traducciones
12.
Ecotoxicol Environ Saf ; 236: 113494, 2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-35413622

RESUMEN

Cadmium could induce cell apoptosis, probably related to the dysfunction of the mitochondrial respiratory chain. The human renal proximal tubule (HK-2) was used to explore the mechanism of mitochondrial respiratory chain dysfunction during apoptosis induced by cadmium chloride (CdCl2). Cell viability was evaluated by cell proliferation assay and different concentrations of 60, 80 and 100 µM were selected to evaluate the mitochondrial toxicity of CdCl2 respectively. Under the CdCl2 treatment for 24 h, the mitochondrial reactive oxygen species (ROS) of HK-2 cells increased and the superoxide dismutase (SOD) activity was inhibited at the above three concentrations separately. Both ATP content and mitochondrial membrane potential decreased significantly at 100 µM concentration. The levels of procaspase-3 and Bcl-2 had fallen in a concentration-dependent manner and Bax was significantly increased at 60, 80 and 100 µM concentration compared with no CdCl2 treatment respectively, which activated the mitochondrial apoptosis pathway. N-acetyl-cysteine (NAC) could partially resist CdCl2-induced cell apoptosis, while myxothiazol (Myx) promoted the process. Mitochondria relative alterations manifested as inhibition of complex III and V. In addition, both the quantity of mitochondrial coenzyme Q-binding protein CoQ10 homolog B (CoQ10B) and cytochrome c (Cyt c) had decreased significantly. Taken together, CdCl2 induced HK-2 apoptosis due to the mitochondrial respiratory chain dysfunction by reducing the CoQ10B level, offering a novel evaluating indicator for the environmental toxicity of CdCl2.


Asunto(s)
Apoptosis , Cloruro de Cadmio , Cadmio/toxicidad , Cloruro de Cadmio/toxicidad , Transporte de Electrón , Humanos , Potencial de la Membrana Mitocondrial , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo
13.
Int J Environ Health Res ; 32(11): 2376-2384, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34365848

RESUMEN

Trichloroacetic acid (TCA) is a common non-volatile by-product of chlorination disinfection for drinking water. It is necessary to know the epigenetic toxicity and mechanisms for establishing safe exposure limit for environmental TCA exposure. This study explored the histone modification variations of TCA-treated human hepatocytes L-02 at different time and concentrations. TCA (0.1 mM, 0.3 mM and 0.9 mM) had an inhibitory effect on the growth of L-02 cells, with no significant changes in morphology. Treated with TCA for 24 h and 48 h, L-02 cells showed decreased mRNA and protein level of histone deacetylases (HDACs), but increased after 72 h. The downregulation of HDACs in early stage of TCA exposure might be one of the important reasons for the increase of H3K9ac level. These changes of histone modification may serve as early epigenetic biomarkers for TCA exposure and the related diseases, offering the safe environmental exposure concentration reference.


Asunto(s)
Agua Potable , Ácido Tricloroacético , Hepatocitos/metabolismo , Código de Histonas , Histona Desacetilasas/metabolismo , Histona Desacetilasas/farmacología , Humanos , ARN Mensajero/metabolismo , ARN Mensajero/farmacología , Ácido Tricloroacético/metabolismo , Ácido Tricloroacético/toxicidad
14.
World J Microbiol Biotechnol ; 38(7): 121, 2022 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-35635589

RESUMEN

A magnetosome-producing bacterium Acidithiobacillus ferrooxidans BYM (At. ferrooxidans BYM) was isolated and magnetically screened. The magnetosome yield from 0.5896 to 13.1291 mg/g was achieved under different aeration rates, ferrous sulfate, ammonium sulfate, and gluconic acid concentrations at 30 â„ƒ. TEM observed 6-9 magnetosomes in size of 20-80 nm irregularly dispersed in a cell. STEM-EDXS and HRTEM-FFT implied that the elongated-prismatic magnetite magnetosomes with {110} crystal faces grown along the [111] direction. Whole-genome sequencing and annotation of BYM showed that 3.2 Mb chromosome and 47.11 kb plasmid coexisted, and 322 genes associated with iron metabolism were discovered. Ten genes shared high similarity with magnetosome genes were predicted, providing sufficient evidence for the magnetosome-producing potential of BYM. Accordingly, we first proposed a hypothetic model of magnetosome formation including vesicle formation, iron uptake and mineralization, and magnetite crystal maturation in At. ferrooxidans. These indicated that At. ferrooxidans BYM would be used as a commercial magnetosome-producing microorganism.


Asunto(s)
Acidithiobacillus , Magnetosomas , Acidithiobacillus/genética , Acidithiobacillus/metabolismo , Óxido Ferrosoférrico/metabolismo , Hierro/metabolismo , Magnetosomas/química
15.
Carcinogenesis ; 42(3): 481-492, 2021 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-33315089

RESUMEN

Mitochondria-localized sirtuin 4 (SIRT4) is associated with malignant phenotypes in colorectal cancer (CRC). However, the molecular mechanisms that drive SIRT4-mediated carcinogenesis are unclear. Initially, we confirmed expression of SIRT4 in CRC through public database and in CRC patient tissues using quantitative real-time reverse transcription PCR. We established HCT116 colorectal cells that overexpressed SIRT4 and HT29 cells were transfected with plasmids bearing a small interfering RNA construct to silence SIRT4. Assays to determine the malignant phenotypes (proliferation, invasion and migration) were performed. Xenograft in vivo models were also constructed. A protein interactome network was built using differentially expressed proteins identified using the liquid chromatography/tandem mass spectrophotometry, the findings of which were confirmed using co-immunoprecipitation, western blotting and phenotype rescue experiments. Decreased SIRT4 expression was associated with malignant phenotypes in vitro and in vivo. The ribosomal biogenesis pathway was enriched in the interactome network. SIRT4 suppression activated glutaminase, thereby initiating AKT activation. Our research provided novel insights into the molecular mechanisms underlying CRC, and identified that SIRT4 exerts its antitumor activity in CRC possibly dependent on glutaminase to inhibit proliferation, migration and invasion via the AKT/GSK3ß/CyclinD1 pathway.


Asunto(s)
Carcinogénesis/patología , Neoplasias Colorrectales/patología , Glutaminasa/metabolismo , Proteínas Mitocondriales/metabolismo , Sirtuinas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Movimiento Celular , Proliferación Celular , Colectomía , Colon/patología , Colon/cirugía , Neoplasias Colorrectales/cirugía , Ciclina D1/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Células HCT116 , Células HT29 , Humanos , Ratones , Proteínas Mitocondriales/genética , Invasividad Neoplásica , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Sirtuinas/genética , Proteínas Supresoras de Tumor/genética , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Anal Chem ; 93(23): 8273-8280, 2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-34061492

RESUMEN

A microfluidic magnetic analyte delivery (µMAD) technique was developed to realize sample preparation and ultrasensitive biomarker detection. A simply designed microfluidic device was employed to carry out this technique, including a poly(dimethylsiloxane)-glass hybrid microchip having four straight rectangular channels and a permanent magnet. In the µMAD process, functionalized magnetic beads (MBs) were used to recognize and isolate analytes from a complex sample matrix, deliver analytes into tiny microchannels, and preconcentrate analytes in the magnetic trapping/detection region for in situ fluorescence detection. In the feasibility study and sensitivity optimization, horseradish peroxidase-labeled MBs were used, and critical parameters for the signal amplification performance of µMAD were carefully evaluated. At optimized conditions, a sensitivity improvement of at least 2 orders of magnitude was achieved. As a proof of concept, µMAD was combined with the enzyme-linked immunosorbent assay (ELISA), while carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), and interleukin 6 (IL-6) were selected as model biomarkers. The limits of detection (LODs) of µMAD-ELISA were as low as 0.29 pg/mL for CEA, 0.047 pg/mL for PSA, and 0.021 pg/mL for IL-6, which corresponded to an over 200-fold reduction compared to their commercial ELISA results. Meanwhile, µMAD-ELISA revealed high selectivity and reproducibility. In clinical sample analysis, good accuracy was acquired for human serum analysis relative to commercial ELISA kits, and satisfied recoveries of 85.1-102% with RSDs of 1.7-9.8% for IL-6 and 84.7-113% with RSDs of 3.2-8.3% for interferon-γ were obtained. This ultrasensitive and easy operation technique provides a valuable approach for trace-level biomarker detection for practical applications.


Asunto(s)
Biomarcadores/análisis , Microfluídica , Antígeno Carcinoembrionario/análisis , Ensayo de Inmunoadsorción Enzimática , Humanos , Interleucina-6/análisis , Límite de Detección , Masculino , Antígeno Prostático Específico/análisis , Reproducibilidad de los Resultados
17.
Plant Cell ; 30(1): 48-66, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29263085

RESUMEN

Inflorescence architecture is a key determinant of yield potential in many crops and is patterned by the organization and developmental fate of axillary meristems. In cereals, flowers and grain are borne from spikelets, which differentiate in the final iteration of axillary meristem branching. In Setaria spp, inflorescence branches terminate in either a spikelet or a sterile bristle, and these structures appear to be paired. In this work, we leverage Setaria viridis to investigate a role for the phytohormones brassinosteroids (BRs) in specifying bristle identity and maintaining spikelet meristem determinacy. We report the molecular identification and characterization of the Bristleless1 (Bsl1) locus in S. viridis, which encodes a rate-limiting enzyme in BR biosynthesis. Loss-of-function bsl1 mutants fail to initiate a bristle identity program, resulting in homeotic conversion of bristles to spikelets. In addition, spikelet meristem determinacy is altered in the mutants, which produce two florets per spikelet instead of one. Both of these phenotypes provide avenues for enhanced grain production in cereal crops. Our results indicate that the spatiotemporal restriction of BR biosynthesis at boundary domains influences meristem fate decisions during inflorescence development. The bsl1 mutants provide insight into the molecular basis underlying morphological variation in inflorescence architecture.


Asunto(s)
Brasinoesteroides/farmacología , Diferenciación Celular/efectos de los fármacos , Inflorescencia/citología , Meristema/citología , Setaria (Planta)/citología , Alelos , Sistema Enzimático del Citocromo P-450/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Sitios Genéticos , Inflorescencia/efectos de los fármacos , Inflorescencia/ultraestructura , Meristema/efectos de los fármacos , Modelos Biológicos , Mutación/genética , Fenotipo , Filogenia , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Setaria (Planta)/efectos de los fármacos , Setaria (Planta)/genética , Setaria (Planta)/ultraestructura , Transducción de Señal/efectos de los fármacos
18.
Arch Toxicol ; 95(11): 3497-3513, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34510229

RESUMEN

Cadmium (Cd) has been reported to induce kidney damage by triggering oxidative stress and inflammation. The NLR family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated a role in the pathogenesis of inflammation. However, the connection between Cd and NLRP3 inflammasome in the development of renal inflammation remains unknown. In this study, in vitro experiments based on the telomerase-immortalized human renal proximal-tubule epithelial cell line (RPTEC/TERT1) were carried out. Results revealed that CdCl2 (2-8 µM) increased ROS production and activated NLRP3, thereby enhancing secretion of IL-1ß and IL-18 (P < 0.05). Knock-down of NLRP3 rescued the RPTEC/TERT1 cells from Cd-induced inflammatory damage. Cd activated the MAPK/NF-κB signaling pathway in RPTEC/TERT1 cells (P < 0.05). In addition, treatment with N-acetylcysteine (NAC) improved inflammation and blocked the upregulation of the MAPK/NF-κB signaling pathway. Pre-treatment with MAPK and NF-κB inhibitors also suppressed NLRP3 inflammasome activation (P < 0.05). Moreover, CdCl2 (25-00 mg/L) stimulated the MAPK/NF-κB signaling pathway, activated the NLRP3 inflammasome, and increased inflammatory response (P < 0.05) leading to renal injury in rats. Exposure to cadmium elevated serum levels of NLRP3 and IL-1ß in populations (P < 0.05). Further analysis found that serum NLRP3 and IL-1ß levels were positively correlated with urine cadmium (UCd) and urine N-acetyl-ß-D-glucosaminidase (UNAG). Overall, Cd induced renal inflammation through the ROS/MAPK/NF-κB signaling pathway by activating the NLRP3 inflammasome. Our research thus provides new insights into the molecular mechanism that NLRP3 contributes to Cd-induced kidney damage.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Cadmio/toxicidad , Inflamación/etiología , Riñón/efectos de los fármacos , Animales , Cadmio/orina , Línea Celular Transformada , Femenino , Humanos , Inflamasomas , Riñón/patología , Túbulos Renales Proximales , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
19.
Ecotoxicol Environ Saf ; 216: 112204, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33845364

RESUMEN

The mitoepigenetic modifications may be closely related to cellular fate. Both the replicative and hydrogen peroxide (H2O2)-induced premature senescence models were used to detect the mitochondrial biological characteristics and the epigenetic factors during senescence of human embryonic lung fibroblasts. The mitochondrial quantity was decreased in two senescence stages, while the mitochondrial DNA (mtDNA) copy number was increased significantly and the methyltransferases activity likewise. And the acute mtROS accumulation could launch premature senescence. Later, the persistent premature senescence owned the higher level of adenosine triphosphate (ATP) and mitochondrial 5-methylcytosine (mt-5-mC), and the less level of 8-hydroxydeoxyguanosine (8-OHdG) than those of replicative senescence. The mtDNA methylation-related enzymes, binding protein and the mitochondrial transcription regulators presented the differentially expressed profiles in both senescent states. Interestingly, the hypermethylation in the CpG region of mitochondrial transcription factor B2 (TFB2M) contributed to its downregulation of mRNA level in replicative senescence. The alterations of the mitochondrial biological functions and mtDNA features would be novel candidate biomarkers involved in cellular senescence. The specific methylation status of mtDNA may also have a crosstalk with oxidative stress to the mitochondrial function, contributing to cellular senescence.

20.
J Trop Pediatr ; 67(6)2021 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-34966947

RESUMEN

BACKGROUND: This study is aimed to investigate the epidemiological characteristics of rubella in Beijing, Haidian District of China, from 2005 to 2020, providing scientific basis for controlling rubella and the congenital rubella syndrome. METHODS: Data were collected via the legal infectious disease report cards from medical institutions in Haidian, 2005-2020. The descriptive epidemiological methods plus statistical analysis were used to analyze the distribution of rubella in terms of population, time and region. RESULTS: In total, there were 994 cases of rubella in Beijing, Haidian District, with an average incidence of 1.81/100 000. In 2007, it was hit by rubella with the highest incidence up to 8.37/100 000, in the past 16 years. The peak incident of rubella was in spring (March to May). The majority of rubella patients were students and employees (70.1%) who are infected mainly due to the gathering. The majority of patients aged 15-29 years (63.4%). And the male-to-female ratio was 1.45 : 1. Rubella had a feature of spatial aggregation and appeared in all the regions in Haidian. According to Joinpoint regression model, rubella would still exist in the next 3 years with 2-5 new cases per year. CONCLUSIONS: Rubella showed a downshift trend from 2008 to 2014, then a sporadic distribution till 2020 in Haidian. Not completely eliminated yet, it is quite impending to improve people's awareness of preventing rubella and their health literacy mentally and physically in the whole population by means of the policy issuing from government.


Asunto(s)
Rubéola (Sarampión Alemán) , Adolescente , Adulto , Beijing/epidemiología , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Estudios Retrospectivos , Rubéola (Sarampión Alemán)/epidemiología , Rubéola (Sarampión Alemán)/prevención & control , Adulto Joven
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