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1.
Biomacromolecules ; 25(7): 4317-4328, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38829675

RESUMEN

Despite great progress in the hydrogel hemostats and dressings, they generally lack resistant vascular bursting pressure and intrinsic bioactivity to meet arterial massive hemorrhage and proheal wounds. To address the problems, we design a kind of biomimetic and wound microenvironment-modulating PEGylated glycopolypeptide hydrogels that can be easily injected and gelled in ∼10 s. Those glycopolypeptide hydrogels have suitable tissue adhesion of ∼20 kPa, high resistant bursting pressure of ∼150 mmHg, large microporosity of ∼15 µm, and excellent biocompatibility with ∼1% hemolysis ratio and negligible inflammation. They performed better hemostasis in rat liver and rat and rabbit femoral artery bleeding models than Fibrin glue, Gauze, and other hydrogels, achieving fast arterial hemostasis of <20 s and lower blood loss of 5-13%. As confirmed by in vivo wound healing, immunofluorescent imaging, and immunohistochemical and histological analyses, the mannose-modified hydrogels could highly boost the polarization of anti-inflammatory M2 phenotype and downregulate pro-inflammatory tumor necrosis factor-α to relieve inflammation, achieving complete full-thickness healing with thick dermis, dense hair follicles, and 90% collagen deposition. Importantly, this study provides a versatile strategy to construct biomimetic glycopolypeptide hydrogels that can not only resist vascular bursting pressure for arterial massive hemorrhage but also modulate inflammatory microenvironment for wound prohealing.


Asunto(s)
Hemorragia , Hidrogeles , Polietilenglicoles , Cicatrización de Heridas , Animales , Hidrogeles/química , Hidrogeles/farmacología , Ratas , Conejos , Polietilenglicoles/química , Polietilenglicoles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Hemorragia/tratamiento farmacológico , Ratas Sprague-Dawley , Masculino , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Glicopéptidos/química , Glicopéptidos/farmacología , Arteria Femoral/lesiones , Arteria Femoral/efectos de los fármacos
2.
Antonie Van Leeuwenhoek ; 117(1): 102, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012584

RESUMEN

This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7 to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1 to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.


Asunto(s)
Pollos , Reacción en Cadena de la Polimerasa , Enfermedades de las Aves de Corral , ARN Ribosómico 16S , ARN Ribosómico 16S/genética , Animales , Pollos/microbiología , Reacción en Cadena de la Polimerasa/métodos , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/diagnóstico , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , ADN Bacteriano/genética , Análisis de Secuencia de ADN , Filogenia
3.
Langenbecks Arch Surg ; 409(1): 169, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38822914

RESUMEN

INTRODUCTION: Tracheoesophageal fistula (TEF) especially malignant TEF (mTEF) is an uncommon yet critical medical condition necessitating immediate intervention. This life-threatening condition frequently manifests in critically ill patients who are dependent on prolonged mechanical ventilation and are unsuitable candidates for thoracotomy due to their compromised health status. The Management of these mTEF patients remain a significant challenge.This study aimed to evaluate the safety and efficacy of using a cardiac septal occluder for the closure of mTEF. METHODS: 8 patients with mTEF underwent closure surgery using atrial/ventricular septal defect (ASD/VSD) septal occluders at the Respiratory Department of HuBei Yichang Central People's Hospital from 2021 to 2023. The procedure involved percutaneous placement of the occluder through the fistula to achieve closure. RESULTS: The placement of the cardiac septal occluder was successfully achieved with ease and efficiency in all patients. The study demonstrated that the use of cardiac septal occluder therapy in patients with mTEF can alleviate symptoms, improve quality of life, and enhance survival rates, with no significant complications observed. Furthermore, the study provided comprehensive details on surgical indications, preoperative evaluation and diagnosis, selection of occluder, methods of occlusion, and postoperative care. CONCLUSIONS: The application of cardiac septal occluder in the treatment of mTEF is a safe and effective palliative treatment. This approach may be particularly beneficial for patients with a high risk of complications and mortality associated with traditional surgical interventions.


Asunto(s)
Cuidados Paliativos , Dispositivo Oclusor Septal , Fístula Traqueoesofágica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Cuidados Paliativos/métodos , Calidad de Vida , Estudios Retrospectivos , Fístula Traqueoesofágica/cirugía , Fístula Traqueoesofágica/etiología , Resultado del Tratamiento
4.
Biochem Genet ; 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38526708

RESUMEN

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

5.
Proc Natl Acad Sci U S A ; 117(27): 15599-15608, 2020 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-32571930

RESUMEN

2(S)-dihydroxypropanesulfonate (DHPS) is a microbial degradation product of 6-deoxy-6-sulfo-d-glucopyranose (sulfoquinovose), a component of plant sulfolipid with an estimated annual production of 1010 tons. DHPS is also at millimolar levels in highly abundant marine phytoplankton. Its degradation and sulfur recycling by microbes, thus, play important roles in the biogeochemical sulfur cycle. However, DHPS degradative pathways in the anaerobic biosphere are not well understood. Here, we report the discovery and characterization of two O2-sensitive glycyl radical enzymes that use distinct mechanisms for DHPS degradation. DHPS-sulfolyase (HpsG) in sulfate- and sulfite-reducing bacteria catalyzes C-S cleavage to release sulfite for use as a terminal electron acceptor in respiration, producing H2S. DHPS-dehydratase (HpfG), in fermenting bacteria, catalyzes C-O cleavage to generate 3-sulfopropionaldehyde, subsequently reduced by the NADH-dependent sulfopropionaldehyde reductase (HpfD). Both enzymes are present in bacteria from diverse environments including human gut, suggesting the contribution of enzymatic radical chemistry to sulfur flux in various anaerobic niches.


Asunto(s)
Alcanosulfonatos/metabolismo , Anaerobiosis , Bacterias/enzimología , Proteínas Bacterianas/metabolismo , Microbioma Gastrointestinal/fisiología , Biología Computacional , Pruebas de Enzimas , Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/toxicidad , Metilglucósidos/metabolismo , Azufre/metabolismo
6.
Sensors (Basel) ; 23(9)2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37177741

RESUMEN

The current technological world is growing rapidly and each aspect of life is being transformed toward automation for human comfort and reliability. With autonomous vehicle technology, the communication gap between the driver and the traditional vehicle is being reduced through multiple technologies and methods. In this regard, state-of-the-art methods have proposed several approaches for advanced driver assistance systems (ADAS) to meet the requirement of a level-5 autonomous vehicle. Consequently, this work explores the role of textual cues present in the outer environment for finding the desired locations and assisting the driver where to stop. Firstly, the driver inputs the keywords of the desired location to assist the proposed system. Secondly, the system will start sensing the textual cues present in the outer environment through natural language processing techniques. Thirdly, the system keeps matching the similar keywords input by the driver and the outer environment using similarity learning. Whenever the system finds a location having any similar keyword in the outer environment, the system informs the driver, slows down, and applies the brake to stop. The experimental results on four benchmark datasets show the efficiency and accuracy of the proposed system for finding the desired locations by sensing textual cues in autonomous vehicles.

7.
Biochem Cell Biol ; 98(4): 511-517, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32648768

RESUMEN

There is an increasing body of evidence indicating the important roles of miRNAs in the progression of pituitary adenoma. Recent studies have shown decreased expression and tumor suppressive function of miR-448 in cancers; however, the clinical significance of miR-448 in pituitary adenoma has remained largely unknown. In our study, we found that miR-448 was down-regulated in pituitary adenoma tissues and cell lines. Overexpression of miR-448 significantly inhibited the proliferation and migration of pituitary adenoma cells. Increased cell apoptosis was also observed with overexpression of miR-448. To further understand the mechanisms behind the regulation of pituitary adenoma by miR-448 in, the targets of miR-448 were predicted using the bioinformatics tools. B cell lymphoma 2 (BCL2) was identified as a target of miR-448. MiR-448 bound the 3'-untranslated region (UTR) of BCL2 and inhibited the expression of BCL2 in pituitary adenoma cells. There was a consistent and significantly negative correlation between the level of miR-448 and BCL2 in pituitary adenoma tissues. When BCL2 was highly expressed, the inhibitory impact of miR-448 on the proliferation and apoptosis of pituitary adenoma cells was significantly inhibited. Collectively, our findings emphasize the significance of the miR-448-BCL2 axis in the development of pituitary adenoma, highlighting the potential therapeutic significance of miR-448 in pituitary adenoma.


Asunto(s)
Adenoma/metabolismo , MicroARNs/metabolismo , Neoplasias Hipofisarias/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Adenoma/genética , Adenoma/patología , Apoptosis/fisiología , Línea Celular Tumoral , Proliferación Celular/fisiología , Humanos , MicroARNs/genética , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Transducción de Señal
8.
Appl Environ Microbiol ; 85(13)2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31053578

RESUMEN

The effectiveness of antibiotics has been challenged by the increasing frequency of antimicrobial resistance (AMR), which has emerged as a major threat to global health. Despite its negative impact on the development of AMR, there are few effective strategies for reducing AMR in food-producing animals. Using whole-genome sequencing and comparative genomics of 36 multidrug-resistant (MDR) Escherichia coli strains isolated from beef cattle with no previous exposure to antibiotics, we obtained results suggesting that the occurrence of MDR E. coli also arises in animals with no antibiotic selective pressure. Extended-spectrum-ß-lactamase-producing E. coli strains with enhanced virulence capacities for toxin production and adherence have evolved, which implies important ramifications for animal and human health. Gene exchanges by conjugative plasmids and insertion elements have driven widespread antibiotic resistance in clinically relevant pathogens. Phylogenetic relatedness of E. coli strains from various geographic locations and hosts, such as animals, environmental sources, and humans, suggests that transmission of MDR E. coli strains occurs intercontinentally without host barriers.IMPORTANCE Multidrug-resistant (MDR) Escherichia coli isolates pose global threats to public health due to the decreasing availability of treatment options. To better understand the characteristics of MDR E. coli isolated from food-producing animals with no antibiotic exposure, we employed genomic comparison, high-resolution phylogenetics, and functional characterization. Our findings highlight the potential capacity of MDR E. coli to cause severe disease and suggest that these strains are widespread intercontinentally. This study underlines the occurrence of MDR E. coli in food-producing animals raised without antibiotic use, which has alarming, critical ramifications within animal and human medical practice.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli/genética , beta-Lactamasas/genética , Animales , Bovinos , Enfermedades de los Bovinos/microbiología , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/veterinaria , Genómica , Filogenia , Secuenciación Completa del Genoma/veterinaria , beta-Lactamasas/metabolismo
9.
Nat Chem Biol ; 13(4): 381-388, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28135235

RESUMEN

Polycomb repressive complex 2 (PRC2) consists of three core subunits, EZH2, EED and SUZ12, and plays pivotal roles in transcriptional regulation. The catalytic subunit EZH2 methylates histone H3 lysine 27 (H3K27), and its activity is further enhanced by the binding of EED to trimethylated H3K27 (H3K27me3). Small-molecule inhibitors that compete with the cofactor S-adenosylmethionine (SAM) have been reported. Here we report the discovery of EED226, a potent and selective PRC2 inhibitor that directly binds to the H3K27me3 binding pocket of EED. EED226 induces a conformational change upon binding EED, leading to loss of PRC2 activity. EED226 shows similar activity to SAM-competitive inhibitors in blocking H3K27 methylation of PRC2 target genes and inducing regression of human lymphoma xenograft tumors. Interestingly, EED226 also effectively inhibits PRC2 containing a mutant EZH2 protein resistant to SAM-competitive inhibitors. Together, we show that EED226 inhibits PRC2 activity via an allosteric mechanism and offers an opportunity for treatment of PRC2-dependent cancers.


Asunto(s)
Antineoplásicos/farmacología , Histonas/metabolismo , Lisina/metabolismo , Complejo Represivo Polycomb 2/antagonistas & inhibidores , Sulfonas/química , Sulfonas/farmacología , Triazoles/química , Triazoles/farmacología , Regulación Alostérica/efectos de los fármacos , Animales , Antineoplásicos/química , Sitios de Unión/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Histonas/química , Humanos , Lisina/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Modelos Moleculares , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Complejo Represivo Polycomb 2/química , Complejo Represivo Polycomb 2/metabolismo , Relación Estructura-Actividad , Sulfonas/metabolismo , Triazoles/metabolismo , Células Tumorales Cultivadas
10.
Mol Cell Biochem ; 442(1-2): 11-18, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-28887702

RESUMEN

In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3. These findings provide evidence that necroptosis plays a significant role in cardiomyocyte death and it is a major pathway for cell death in acute VMC. Blocking the necroptosis pathway may serve as a new therapeutic option for the treatment of acute viral myocarditis.


Asunto(s)
Miocarditis/metabolismo , Miocitos Cardíacos/metabolismo , Enfermedad Aguda , Animales , Muerte Celular , Infecciones por Coxsackievirus/metabolismo , Infecciones por Coxsackievirus/patología , Enterovirus Humano B/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Miocarditis/patología , Miocarditis/virología , Miocitos Cardíacos/patología , Miocitos Cardíacos/virología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo
11.
Glob Chang Biol ; 23(11): 4828-4839, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28346724

RESUMEN

Macroalgae contribute approximately 15% of the primary productivity in coastal marine ecosystems, fix up to 27.4 Tg of carbon per year, and provide important structural components for life in coastal waters. Despite this ecological and commercial importance, direct measurements and comparisons of the short-term responses to elevated pCO2 in seaweeds with different life-history strategies are scarce. Here, we cultured several seaweed species (bloom forming/nonbloom forming/perennial/annual) in the laboratory, in tanks in an indoor mesocosm facility, and in coastal mesocosms under pCO2 levels ranging from 400 to 2,000 µatm. We find that, across all scales of the experimental setup, ephemeral species of the genus Ulva increase their photosynthesis and growth rates in response to elevated pCO2 the most, whereas longer-lived perennial species show a smaller increase or a decrease. These differences in short-term growth and photosynthesis rates are likely to give bloom-forming green seaweeds a competitive advantage in mixed communities, and our results thus suggest that coastal seaweed assemblages in eutrophic waters may undergo an initial shift toward communities dominated by bloom-forming, short-lived seaweeds.


Asunto(s)
Aclimatación , Dióxido de Carbono/metabolismo , Rasgos de la Historia de Vida , Fotosíntesis , Algas Marinas/fisiología , Eutrofización , Algas Marinas/crecimiento & desarrollo
12.
Microb Cell Fact ; 16(1): 233, 2017 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-29274636

RESUMEN

BACKGROUND: As microbial cultures are comprised of heterogeneous cells that differ according to their size and intracellular concentrations of DNA, proteins, and other constituents, the detailed identification and discrimination of the growth phases of bacterial populations in batch culture is challenging. Cell analysis is indispensable for quality control and cell enrichment. METHODS: In this paper, we report the results of our investigation on the use of single-cell Raman spectrometry (SCRS) for real-time analysis and prediction of cells in different growth phases during batch culture of Lactobacillus (L.) casei Zhang. A targeted analysis of defined cell growth phases at the level of the single cell, including lag phase, log phase, and stationary phase, was facilitated by SCRS. RESULTS: Spectral shifts were identified in different states of cell growth that reflect biochemical changes specific to each cell growth phase. Raman peaks associated with DNA and RNA displayed a decrease in intensity over time, whereas protein-specific and lipid-specific Raman vibrations increased at different rates. Furthermore, a supervised classification model (Random Forest) was used to specify the lag phase, log phase, and stationary phase of cells based on SCRS, and a mean sensitivity of 90.7% and mean specificity of 90.8% were achieved. In addition, the correct cell type was predicted at an accuracy of approximately 91.2%. CONCLUSIONS: To conclude, Raman spectroscopy allows label-free, continuous monitoring of cell growth, which may facilitate more accurate estimates of the growth states of lactic acid bacterial populations during fermented batch culture in industry.


Asunto(s)
Lacticaseibacillus casei/citología , Lacticaseibacillus casei/crecimiento & desarrollo , Espectrometría Raman/métodos , Técnicas de Cultivo Celular por Lotes
13.
J Psycholinguist Res ; 46(6): 1529-1548, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28639174

RESUMEN

This study revisited Reid's (1987) perceptual learning style preference questionnaire (PLSPQ) in an attempt to answer whether the PLSPQ fits in the Chinese-as-a-second-language (CSL) context. If not, what are CSL learners' learning styles drawing on the PLSPQ? The PLSPQ was first re-examined through reliability analysis and confirmatory factor analysis (CFA) with 224 CSL learners. The results showed that Reid's six-factor PLSPQ could not satisfactorily explain the CSL learners' learning styles. Exploratory factor analyses were, therefore, performed to explore the dimensionality of the PLSPQ in the CSL context. A four-factor PLSPQ was successfully constructed including auditory/visual, kinaesthetic/tactile, group, and individual styles. Such a measurement model was cross-validated through CFAs with 118 CSL learners. The study not only lends evidence to the literature that Reid's PLSPQ lacks construct validity, but also provides CSL teachers and learners with insightful and practical guidance concerning learning styles. Implications and limitations of the present study are discussed.


Asunto(s)
Lenguaje , Aprendizaje , Adolescente , Adulto , China , Análisis Factorial , Femenino , Humanos , Masculino , Multilingüismo , Reproducibilidad de los Resultados , Universidades , Adulto Joven
14.
J Cell Physiol ; 230(11): 2640-6, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25639860

RESUMEN

Adrenoreceptors (ARs) are widely expressed and play essential roles throughout the body. Different subtype adrenoceptors elicit distinct effects on cell proliferation, but knowledge remains scarce about the subtype-specific effects of ß2-ARs on the proliferation of embryonic pluripotent stem (PS) cells that represent different characteristics of proliferation and cell cycle regulation with the somatic cells. Herein, we identified a ß2-AR/AC/cAMP/PKA signaling pathway in embryonic PS cells and found that the pathway stimulation inhibited proliferation and cell cycle progression involving modulating the stem cell growth and cycle regulatory machinery. Embryonic stem (ES) cells and embryonal carcinoma stem (ECS) cells expressed functional ß-ARs coupled to AC/cAMP/PKA signaling. Agonistic activation of ß-ARs led to embryonic PS cell cycle arrest and proliferation inhibition. Pharmacological and genetic analyzes using receptor subtype blocking and RNA interference approaches revealed that this effect selectively depended on ß2-AR signaling involving the regulation of AKT, ERK, Rb, and Cyclin E molecules. Better understanding of the effects of ß2-ARs on embryonic PS cell proliferation and cycle progression may provide new insights into stem cell biology and afford the opportunity for exploiting more selective ligands targeting the receptor subtype for the modulation of stem cells.


Asunto(s)
Células Madre Embrionarias/citología , Proteína Oncogénica v-akt/genética , Células Madre Pluripotentes/citología , Receptores Adrenérgicos beta 2/genética , Agonistas de Receptores Adrenérgicos beta 2/farmacología , Puntos de Control del Ciclo Celular/genética , Proliferación Celular/genética , AMP Cíclico/genética , AMP Cíclico/metabolismo , Células Madre Embrionarias/metabolismo , Humanos , Proteína Oncogénica v-akt/biosíntesis , Células Madre Pluripotentes/metabolismo , Interferencia de ARN , Receptores Adrenérgicos beta 2/metabolismo , Transducción de Señal/efectos de los fármacos
15.
Proc Natl Acad Sci U S A ; 109(52): 21360-5, 2012 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-23236167

RESUMEN

Ezh2 (Enhancer of zeste homolog 2) protein is the enzymatic component of the Polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 of histone H3 (H3K27) and regulates cell proliferation and differentiation during embryonic development. Recently, hot-spot mutations of Ezh2 were identified in diffused large B-cell lymphomas and follicular lymphomas. To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we developed a potent and selective small molecule inhibitor, EI1, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine. EI1-treated cells exhibit genome-wide loss of H3K27 methylation and activation of PRC2 target genes. Furthermore, inhibition of Ezh2 by EI1 in diffused large B-cell lymphomas cells carrying the Y641 mutations results in decreased proliferation, cell cycle arrest, and apoptosis. These results provide strong validation of Ezh2 as a potential therapeutic target for the treatment of cancer.


Asunto(s)
Linfoma de Células B Grandes Difuso/patología , Complejo Represivo Polycomb 2/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Embrión de Mamíferos/citología , Proteína Potenciadora del Homólogo Zeste 2 , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Inactivación de Genes , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Linfoma de Células B Grandes Difuso/genética , Metilación/efectos de los fármacos , Ratones , Mutación/genética , Fenotipo , Complejo Represivo Polycomb 2/metabolismo , Bibliotecas de Moléculas Pequeñas/química , Ensayo de Tumor de Célula Madre , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética
16.
Food Res Int ; 180: 114100, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38395570

RESUMEN

Infant and toddler food (ITF), including powdered infant and follow-up formula (PIFF) and complementary food (CF), provides the majority of early-life nutrients for young children. As infants and toddlers are more vulnerable to foodborne diseases, the safety concern of ITF is the ultimate priority. However, nationwide surveillance for the presence of hazards, specifically microbiological hazards, in the Chinese ITF is partially known, posing a significant knowledge gap for risk ranking. Most importantly, the related regional surveys were largely published in Chinese, making the data unavailable for global sharing. To bridge these gaps, we screened 5,306 publications and conducted a comprehensive meta-analysis for microbiological hazards using 129 qualified studies. The four most reported microbiological hazards in ITF were Bacillus cereus (13.4 %), Cronobacter (4.8 %), Staphylococcus aureus (1.3 %), and Salmonella (1.1 %). B. cereus is a risk factor in ITF, specifically in PIFF, cereals, and ready-to-eat food. The prevalence of B. cereus was high in Northern and Southern China, while the prevalence of Cronobacter was high in Central China. Cronobacter is a microbiological hazard, specifically in PIFF, with a prevalence of 3.0 %. Interestingly, the prevalence dynamics of Cronobacter and B. cereus in ITF were rising and stable, respectively, whereas the prevalence of S. aureus and Salmonella decreased over time. Together, our analysis will promote the global sharing of these critical findings and may guide future policy making.


Asunto(s)
Cronobacter , Enfermedades Transmitidas por los Alimentos , Lactante , Humanos , Preescolar , Microbiología de Alimentos , Staphylococcus aureus , Enfermedades Transmitidas por los Alimentos/epidemiología , Enfermedades Transmitidas por los Alimentos/microbiología , Salmonella , Fórmulas Infantiles , China
17.
Microbiol Spectr ; 12(1): e0261723, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38078715

RESUMEN

IMPORTANCE: Pseudorabies virus (PRV) causes high mortality and miscarriage rates in the infected swine, and the eradication policy coupled with large-scale vaccination of live attenuated vaccines has been adopted globally against PRV. Differential diagnosis of the vaccinated and infected swine is highly demanded. Our multienzyme isothermal rapid amplification (MIRA)-Cas12a detection method described in this study can diagnose PRV with a superior sensitivity comparable to the quantitative PCR (qPCR) and a competitive detection speed (only half the time as qPCR needs). The portable feature and the simple procedure of MIRA-Cas12a make it easier to deploy for clinical diagnosis, even in resource-limited settings. The MIRA-Cas12a method would provide immediate and accurate diagnostic information for policymakers to respond promptly.


Asunto(s)
Herpesvirus Suido 1 , Seudorrabia , Enfermedades de los Porcinos , Animales , Porcinos , Herpesvirus Suido 1/genética , Seudorrabia/diagnóstico , Seudorrabia/prevención & control , Sistemas CRISPR-Cas , Diagnóstico Diferencial , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/prevención & control , Vacunas Atenuadas , Anticuerpos Antivirales
18.
Med Image Anal ; 92: 103045, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38071865

RESUMEN

Automatic and accurate dose distribution prediction plays an important role in radiotherapy plan. Although previous methods can provide promising performance, most methods did not consider beam-shaped radiation of treatment delivery in clinical practice. This leads to inaccurate prediction, especially on beam paths. To solve this problem, we propose a beam-wise dose composition learning (BDCL) method for dose prediction in the context of head and neck (H&N) radiotherapy plan. Specifically, a global dose network is first utilized to predict coarse dose values in the whole-image space. Then, we propose to generate individual beam masks to decompose the coarse dose distribution into multiple field doses, called beam voters, which are further refined by a subsequent beam dose network and reassembled to form the final dose distribution. In particular, we design an overlap consistency module to keep the similarity of high-level features in overlapping regions between different beam voters. To make the predicted dose distribution more consistent with the real radiotherapy plan, we also propose a dose-volume histogram (DVH) calibration process to facilitate feature learning in some clinically concerned regions. We further apply an edge enhancement procedure to enhance the learning of the extracted feature from the dose falloff regions. Experimental results on a public H&N cancer dataset from the AAPM OpenKBP challenge show that our method achieves superior performance over other state-of-the-art approaches by significant margins. Source code is released at https://github.com/TL9792/BDCLDosePrediction.


Asunto(s)
Neoplasias de Cabeza y Cuello , Radioterapia de Intensidad Modulada , Humanos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Neoplasias de Cabeza y Cuello/radioterapia
19.
Artículo en Inglés | MEDLINE | ID: mdl-38669174

RESUMEN

Accurate segmentation of brain structures is crucial for analyzing longitudinal changes in children's brains. However, existing methods are mostly based on models established at a single time-point due to difficulty in obtaining annotated data and dynamic variation of tissue intensity. The main problem with such approaches is that, when conducting longitudinal analysis, images from different time points are segmented by different models, leading to significant variation in estimating development trends. In this paper, we propose a novel unified model with co-registration framework to segment children's brain images covering neonates to preschoolers, which is formulated as two stages. First, to overcome the shortage of annotated data, we propose building gold-standard segmentation with co-registration framework guided by longitudinal data. Second, we construct a unified segmentation model tailored to brain images at 0-6 years old through the introduction of a convolutional network (named SE-VB-Net), which combines our previously proposed VB-Net with Squeeze-and-Excitation (SE) block. Moreover, different from existing methods that only require both T1- and T2-weighted MR images as inputs, our designed model also allows a single T1-weighted MR image as input. The proposed method is evaluated on the main dataset (320 longitudinal subjects with average 2 time-points) and two external datasets (10 cases with 6-month-old and 40 cases with 20-45 weeks, respectively). Results demonstrate that our proposed method achieves a high performance (>92%), even over a single time-point. This means that it is suitable for brain image analysis with large appearance variation, and largely broadens the application scenarios.

20.
mLife ; 3(1): 156-160, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38827503

RESUMEN

Invasive nontyphoidal Salmonella (iNTS) causes significant concern with ~15% morbidity, affecting populations mainly in African countries. However, iNTS infections among the Chinese pediatric population remain largely unknown. Here, we conducted a genomic investigation to study pediatric iNTS infections in a Chinese hospital. iNTS isolates accounted for 15.2% (18/119) of all nontyphoidal Salmonella (NTS) strains. Compared to non-iNTS isolates, iNTS isolates harbored a lower prevalence of antimicrobial-resistant genes of fluoroquinolones and ß-lactams, as well as disinfectant determinants and plasmids, but carried a significantly higher prevalence of cdtB, faeCDE, and tcpC genes. Importantly, we detected an emerging serovar Goldcoast as the predominant iNTS serovar locally. By integrating 320 global Goldcoast genomes based on the One Health samplings, we conducted nationwide phylogenomic tracking and detected repeated human-to-human transmission events among iNTS cases caused by an underestimated serovar Goldcoast. Together, our exploratory genomic approach highlights a new trend in pediatric iNTS infections.

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