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1.
Mol Ther ; 31(7): 2132-2153, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37194236

RESUMEN

To leverage complementary mechanisms for cancer cell removal, we developed a novel cell engineering and therapeutic strategy co-opting phagocytic clearance and antigen presentation activity into T cells. We engineered a chimeric engulfment receptor (CER)-1236, which combines the extracellular domain of TIM-4, a phagocytic receptor recognizing the "eat me" signal phosphatidylserine, with intracellular signaling domains (TLR2/TIR, CD28, and CD3ζ) to enhance both TIM-4-mediated phagocytosis and T cell cytotoxic function. CER-1236 T cells demonstrate target-dependent phagocytic function and induce transcriptional signatures of key regulators responsible for phagocytic recognition and uptake, along with cytotoxic mediators. Pre-clinical models of mantle cell lymphoma (MCL) and EGFR mutation-positive non-small cell lung cancer (NSCLC) demonstrate collaborative innate-adaptive anti-tumor immune responses both in vitro and in vivo. Treatment with BTK (MCL) and EGFR (NSCLC) inhibitors increased target ligand, conditionally driving CER-1236 function to augment anti-tumor responses. We also show that activated CER-1236 T cells exhibit superior cross-presentation ability compared with conventional T cells, triggering E7-specific TCR T responses in an HLA class I- and TLR-2-dependent manner, thereby overcoming the limited antigen presentation capacity of conventional T cells. Therefore, CER-1236 T cells have the potential to achieve tumor control by eliciting both direct cytotoxic effects and indirect-mediated cross-priming.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Adulto , Linfocitos T , Reactividad Cruzada , Fosfatidilserinas , Antígenos de Neoplasias , Receptores ErbB , Inmunoterapia Adoptiva , Receptores de Antígenos de Linfocitos T/genética
2.
J Gerontol Nurs ; 50(5): 43-49, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38691116

RESUMEN

PURPOSE: To explore care requirements of older adults with urinary incontinence (UI) and contributing factors. METHOD: This cross-sectional study used the Older Adults Urinary Incontinence Care Needs Inventory to survey participants with UI in three large-scale tertiary hospitals located in Guangzhou City, China, from January 2023 to November 2023. Statistical analyses, including analysis of variance, t tests, correlation analyses, and linear regression models, were conducted to assess factors influencing participants' care needs. RESULTS: A total of 530 older adults with UI participated in the survey and mean standardized score for overall care needs was 78.65 (SD = 5.01), with mean scores for each dimension ranging from 70.88 (SD = 10.55) for social participation needs to 82.45 (SD = 7.11) for health education needs. Factors that were found to influence incontinence care needs in older adults included age, literacy level, number of leaks, and type of disease (F = 37.07, adjusted R2 = 0.290, p < 0.001). CONCLUSION: Comprehensive care for older adults with UI, encompassing physiological, psychological, and social aspects, is crucial. It is essential to tailor care to individual needs and characteristics, taking into account factors, such as age and education, to ensure effective care. [Journal of Gerontological Nursing, 50(5), 43-49.].


Asunto(s)
Incontinencia Urinaria , Humanos , Incontinencia Urinaria/enfermería , Estudios Transversales , Anciano , Femenino , Masculino , Anciano de 80 o más Años , China , Persona de Mediana Edad , Encuestas y Cuestionarios , Evaluación de Necesidades , Necesidades y Demandas de Servicios de Salud
3.
J Perianesth Nurs ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38795084

RESUMEN

PURPOSE: Perioperative hypothermia is a common anesthesia-related complication that can result in negative outcomes. Intraoperative active heating can positively impact these outcomes. Therefore this study aimed to investigate the effectiveness of three common heating devices for controlling hypothermia, improving thermal comfort, and reducing anesthesia recovery time. DESIGN: Systematic review and meta-analysis. METHODS: Seven electronic literature databases were searched from the inception date of the databases to March 18, 2022. RevMan 5.4 and Stata 15.1 were used to perform meta-analyses on the obtained data, and the Cochrane Evaluation Manual was used for quality risk assessment of the included studies. FINDINGS: A total of 18 studies involving 1,511 patients undergoing surgery using heating devices were included. In this meta-analysis, a ranking method known as the Surface Under the Cumulative Ranking Curve (SUCRA) was used. SUCRA provides a numerical measure of the effectiveness of treatments, with higher values indicating superior efficacy. Findings demonstrated that the concurrent use of three heating devices led to an elevation in core body temperatures (SUCRA = 69.2%) and enhanced delayed recovery (SUCRA = 88.6%) as compared to the application of a single device. Furthermore, for thermal comfort, the employment of heating blankets proved to be the most effective (SUCRA = 87.8%). CONCLUSIONS: This study showed the core body temperatures and reductions in delayed recovery were greater when three heating devices were used together as compared to use one of them alone. Heating blankets was the most effective option for improving the thermal comfort of patients. Thus, clinicians should opt for appropriate heating equipment according to the type of surgery and the characteristics and needs of patients. The choice of appropriate heating equipment will ensure surgical safety, improve patient comfort, and reduce surgical risks.

4.
Zhongguo Zhong Yao Za Zhi ; 48(4): 908-920, 2023 Feb.
Artículo en Zh | MEDLINE | ID: mdl-36872261

RESUMEN

To clarify the content characteristics of the main active components and mineral elements of Cynomorium songaricum under different habitat conditions, and further explore the relationship between the quality of C. songaricum and habitats, this study took C. songaricum from 25 different habitats in China as the research object, and measured the contents of 8 main active components and 12 mineral elements separately. Diversity analysis, correlation analysis, principal component analysis and cluster analysis were carried out. The results showed that the genetic diversity of total flavonoids, ursolic acid, ether extract, potassium(K), phosphorus(P) and zinc(Zn) in C. songaricum was high. The coefficient of variation of crude polysaccharide, ether extract, gallic acid, protocatechuic aldehyde, catechin, epicatechin, calcium(Ca), sodium(Na), magnesium(Mg), sulfur(S), iron(Fe), manganese(Mn), selenium(Se) and nickel(Ni) were all over 36%, indicating that the quality of C. songaricum was significantly affected by habitats. There were strong synergistic and weak antagonistic effects among the contents of the 8 active components, and complex antagonistic and synergistic effects among the contents of the 12 mineral elements. Principal component analysis revealed that crude polysaccharide, ursolic acid, catechin, epicatechin and total flavonoids could be used as the characteristic components to evaluate the quality of C. songaricum, and Na, copper(Cu), Mn and Ni were the characteristic elements to evaluate the quality of C. songaricum. In cluster ana-lysis, the second group with the main active components as cluster center had better quality in terms of the content of active substances, and the second group with the mineral elements as cluster center had higher utilization potential in the exploitation of mineral elements. This study could provide a basis for resource evaluation and breeding of excellent varieties of C. songaricum in different habitats, and provide a reference for cultivation and identification of C. songaricum.


Asunto(s)
Catequina , Cynomorium , Selenio , Fitomejoramiento , Éteres , Éteres de Etila , Flavonoides , Extractos Vegetales , Ácido Ursólico
5.
Langmuir ; 36(31): 9160-9174, 2020 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-32644798

RESUMEN

Six types of biochar (BSB, CSB, FSB, CFSB, MSB, and TSB) were prepared from different raw materials by loading magnesium ions (Mg2+) via an impregnation process. The adsorption kinetics and thermodynamics of heavy metals at high concentrations were analyzed. The adsorption mechanisms were investigated by zeta potential, scanning electron microscopy-energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and inductively coupled plasma-atomic absorption spectroscopy analyses. The adsorption of heavy metals by BSB, CSB, FSB, CFSB, MSB, and TSB conformed to the Langmuir model and PS-order. The maximum theoretical saturation adsorption capacities for Cd(II), Cu(II), and Pb(II) were 333.33, 238.10, 75.19, 96.15, 66.23, and 185.19 mg·g-1; 370.37, 294.12, 111.11, 169.49, 84.75, and 217.39 mg·g-1; and 302.58, 200.00, 61.73, 90.91, 54.47, and 166.67 mg·g-1, respectively. According to the analysis of the contribution of adsorption, the adsorption process was mainly controlled by cation-π interactions, ion exchange, mineral precipitation, and functional group interactions. Biochars contain ash, functional groups and load a large number of Mg2+, which can form complexes with metal ions and perform strong ion exchange; therefore, mineral precipitation and cation exchange played dominant roles in the adsorption process. The prepared Mg-loaded biochars presented in this research showed excellent adsorption properties for heavy metals and have great potential for practical application; in particular, BSB had the strongest adsorption capacity for the three heavy metal ions.

6.
Asian-Australas J Anim Sci ; 33(11): 1797-1808, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32054193

RESUMEN

OBJECTIVE: This study assessed the effects of probiotics on cecal microbiota, gene expression of intestinal tight junction proteins, and immune response in the cecal tonsil of broiler chickens challenged with Salmonella enterica subsp. enterica. METHODS: One-day-old broiler chickens (n = 240) were randomly allocated to four treatments: negative control (Cont), multi-strain probiotic-treated group (Pro), Salmonella-infected group (Sal), and multi-strain probiotic-treated and Salmonella-infected group (ProSal). All chickens except those in the Cont and Pro groups were gavaged with 1×108 cfu/mL of S. enterica subsp. enterica 4 days after hatching. RESULTS: Our results indicated that body weight, weight gain, and feed conversion ratio of birds were significantly reduced (p<0.05) by Salmonella challenge. Chickens challenged with Salmonella decreased cecal microbial diversity. Chickens in the Sal group exhibited abundant Proteobacteria than those in the Cont, Pro, and ProSal groups. Salmonella infection downregulated gene expression of Occludin, zonula occludens-1 (ZO1), and Mucin 2 in the jejunum and Occludin and Claudin in the ileum. Moreover, the Sal group increased gene expression of interferon-γ (IFN-γ), interleukin-6 (IL-6), IL-1ß, and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF) and reduced levels of transforming growth factor-ß4 and IL-10 compared with the other groups (p<0.05). However, chickens receiving probiotic diets increased Lactobacillaceae abundance and reduced Enterobacteriaceae abundance in the ceca. Moreover, supplementation with probiotics increased the mRNA expression of Occludin, ZO1, and Mucin 2 in the ileum (p<0.05). In addition, probiotic supplementation downregulated the mRNA levels of IFN-γ (p<0.05) and LITAF (p = 0.075) and upregulated IL-10 (p = 0.084) expression in the cecal tonsil. CONCLUSION: The administration of multi-strain probiotics modulated intestinal microbiota, gene expression of tight junction proteins, and immunomodulatory activity in broiler chickens.

7.
Acta Pharmacol Sin ; 40(2): 208-215, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29891858

RESUMEN

MicroRNAs (miRNAs) are widely expressed in organisms and are implicated in the regulation of most biological functions. The present study investigated the association of plasma miRNAs with the clinical outcomes of dual antiplatelet therapy in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Plasma miRNA levels were screened using high-throughput Illumina sequencing to evaluate the antiplatelet efficacy of clopidogrel and aspirin. Six plasma miRNAs (miR-126, miR-130a, miR-27a, miR-106a, miR-21, and miR-142) were associated with clopidogrel-treated platelet aggregation. These miRNAs were validated in a prospective cohort of 1230 CAD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). High plasma miR-142 levels were associated with a high risk of major adverse cardiovascular events (MACE), with a hazard ratio (95% confidence interval) of 1.83 (1.30-2.59) at a false discovery rate of <5%. Multivariable Cox regression analysis revealed that diabetes mellitus, heart failure, calcium channel blocker application, and a high plasma miR-142 level were independent risk factors of MACE. The levels of the six plasma miRNAs were not significantly associated with bleeding events during the 3-year follow-up. In conclusion, plasma miR-142 is potential marker to predict MACE in CAD patients after PCI.


Asunto(s)
Biomarcadores/sangre , Cardiopatías/diagnóstico , Hemorragia/diagnóstico , MicroARNs/sangre , Enfermedades Vasculares/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Aspirina/efectos adversos , Aspirina/uso terapéutico , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Estudios Prospectivos
8.
Biosci Biotechnol Biochem ; 82(5): 836-847, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29517465

RESUMEN

Pteris multifida (PM) and Cortex phellodendri (CP) are medicinal foods used for gastrointestinal protection. Lactic-acid bacteria are probiotics. Salmonella Typhimurium strain ST21-infected mice were used to examine the alleviative effects of two lactic-acid bacteria (LAB) as well as aqueous extracts of PM and CP for a 4-day treatment. CP and LAB decreased fecal ST counts. CP and PM reduced the ST21 count in the blood, intestine, and liver. LAB lowered the ST21 count in the intestine and spleen. CP and LAB decreased the IFN-gamma level; PM lowered the TNF-alpha level; and both LAB and PM reduced the IL-1beta level in serum. PM and CP lowered the IgG level in serum. The data in a macrophage infection model indicate that TNF-alpha was partial involved in this alleviative effects, other mechanisms might be involved. In sum, these novel findings suggest that PM, CP, and LAB probiotics are potential anti-Salmonellae agents.

9.
Biochem Biophys Res Commun ; 491(1): 8-14, 2017 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-28647361

RESUMEN

Apolipoprotein O (ApoO) was recently observed in the cellular mitochondrial inner membrane, which plays a role in mitochondrial function and is associated with myocardiopathy. Empirical information on the physiological functions of apoO is therefore limited. In this study, we aimed to elucidate the effect of apoO on hepatic fatty acid metabolism. An adenoviral vector expressing hApoO was constructed and introduced into chow diet and high-fat diet induced mice and the L02 human hepatoma cell line. High levels of hApoO mRNA and protein were detected in the liver, and the expression of lipid metabolism genes was significantly altered compared with negative controls. The liver function indices (serum ALT and AST) were clearly elevated, and the ultrastructure of cellular mitochondria was distinctly altered in the liver after apoO overexpression. Further, mitochondrial membrane potential decreased with hApoO treatment in L02 cells. These results establish a link between apoO and lipid accumulation and could suggest a new pathway for regulating non-alcoholic fatty liver disease progression.


Asunto(s)
Apolipoproteínas/metabolismo , Hepatocitos/metabolismo , Metabolismo de los Lípidos/fisiología , Lipocalinas/metabolismo , Hígado/metabolismo , Mitocondrias Hepáticas/metabolismo , Animales , Apolipoproteínas/genética , Apolipoproteínas M , Células Cultivadas , Femenino , Hepatocitos/patología , Humanos , Lipocalinas/genética , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mitocondrias Hepáticas/patología
10.
Zhongguo Zhong Yao Za Zhi ; 42(12): 2334-2338, 2017 Jun.
Artículo en Zh | MEDLINE | ID: mdl-28822189

RESUMEN

The content of elements in fifteen different regions of Nitraria roborowskii samples were determined by inductively coupled plasma-atomic emission spectrometry(ICP-OES), and its elemental characteristics were analyzed by principal component analysis. The results indicated that 18 mineral elements were detected in N. roborowskii of which V cannot be detected. In addition, contents of Na, K and Ca showed high concentration. Ti showed maximum content variance, while K is minimum. Four principal components were gained from the original data. The cumulative variance contribution rate is 81.542% and the variance contribution of the first principal component was 44.997%, indicating that Cr, Fe, P and Ca were the characteristic elements of N. roborowskii.Thus, the established method was simple, precise and can be used for determination of mineral elements in N.roborowskii Kom. fruits. The elemental distribution characteristics among N.roborowskii fruits are related to geographical origins which were clearly revealed by PCA. All the results will provide good basis for comprehensive utilization of N.roborowskii.


Asunto(s)
Frutas/química , Minerales/análisis , Streptophyta/química , Oligoelementos/análisis , Análisis de Componente Principal , Análisis Espectral
11.
Int J Syst Evol Microbiol ; 65(Pt 1): 101-106, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25281727

RESUMEN

A Gram-reaction-positive, catalase-negative, facultatively anaerobic, rod-shaped lactic acid bacterium, designated strain S215(T), was isolated from fermented soybean meal. The organism produced d-lactic acid from glucose without gas formation. 16S rRNA gene sequencing results showed that strain S215(T) had 98.74-99.60 % sequence similarity to the type strains of three species of the genus Lactobacillus (Lactobacillus farciminis BCRC 14043(T), Lactobacillus futsaii BCRC 80278(T) and Lactobacillus crustorum JCM 15951(T)). A comparison of two housekeeping genes, rpoA and pheS, revealed that strain S215(T) was well separated from the reference strains of species of the genus Lactobacillus. DNA-DNA hybridization results indicated that strain S215(T) had DNA related to the three type strains of species of the genus Lactobacillus (33-66 % relatedness). The DNA G+C content of strain S215(T) was 36.2 mol%. The cell walls contained peptidoglycan of the d-meso-diaminopimelic acid type and the major fatty acids were C18 : 1ω9c, C16 : 0 and C19 : 0 cyclo ω10c/C19 : 1ω6c. Phenotypic and genotypic features demonstrated that the isolate represents a novel species of the genus Lactobacillus, for which the name Lactobacillus formosensis sp. nov. is proposed. The type strain is S215(T) ( = NBRC 109509(T) = BCRC 80582(T)).


Asunto(s)
Fermentación , Glycine max/microbiología , Lactobacillus/clasificación , Filogenia , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Genes Bacterianos , Ácido Láctico , Lactobacillus/genética , Lactobacillus/aislamiento & purificación , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Peptidoglicano/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
12.
J Sci Food Agric ; 94(3): 576-84, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23824609

RESUMEN

BACKGROUND: Lactobacillus, which has great adhesion ability to intestinal mucosa and is able to hydrolyse plant cell walls, can be used more efficiently as a feed additive. To increase the adhesion ability and display a fungal xylanase on the cell surface of Lactobacillus casei, the Listeria monocytogenes cell-wall-anchoring protein gene, mub, was introduced into L. casei ATCC 393 cells and used as a fusion partner to display the rumen fungal xylanase XynCDBFV on the cell surface of the transformed strains. RESULTS: The transformed strain L. casei pNZ-mub, which harboured mub gene, displayed recombinant Mub on its cell surface and showed greater adhesion ability to Caco-2 cells than the parental strain. The transformed strain L. casei pNZ-mub/xyn, which harboured mub-xynCDBFV fusion gene, acquired the capacity to break down oat spelt xylan and exhibited greater competition ability against the adhesion of L. monocytogenes to Caco-2 cells, in comparison with the parental strain. CONCLUSION: Mub has a potential to be used as a fusion partner to display heterologous proteins on the cell surface of Lactobacillus. Moreover, this is the first report of the successful display of xylanase on the cell surface of Lactobacillus.


Asunto(s)
Adhesión Bacteriana , Proteínas Bacterianas/metabolismo , Genes Bacterianos , Mucosa Intestinal/metabolismo , Lacticaseibacillus casei/enzimología , Listeria monocytogenes/enzimología , Xilosidasas/metabolismo , Animales , Avena/metabolismo , Proteínas Bacterianas/genética , Células CACO-2 , Pared Celular/metabolismo , Aditivos Alimentarios , Proteínas Fúngicas/metabolismo , Humanos , Lacticaseibacillus casei/genética , Listeria monocytogenes/genética , Probióticos , Proteínas Recombinantes/metabolismo , Rumen , Transformación Genética , Xilanos/metabolismo , Xilosidasas/genética
13.
Geriatr Gerontol Int ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38925596

RESUMEN

AIM: This study utilized latent profile analysis to investigate care needs subgroups among older adults with urinary incontinence. METHODS: The "Elderly Urinary Incontinence Care Needs Inventory" surveyed 510 participants in two Guangzhou City hospitals from July 2022 to June 2023. Latent profile analysis created a classification model, and variance and correlation analysis assessed influencing factors. RESULTS: A total of 510 older adults with urinary incontinence participated. The standardized total care needs score was 78.77 ± 5.03, with variations across dimensions: social participation needs scored (71.16 ± 10.32), daily life care needs (78.80 ± 5.51), medical care needs (77.33 ± 12.17), psychological comfort needs (76.97 ± 6.51) and health education needs scored highest (82.67 ± 6.77). Three distinct profiles emerged: "medium," "high SPN-PCN" and "high DLCN-MCN-HEN". The majority belonged to the "high SPN-PCN" profile. Significant correlations were found with age, education, leaks and frequency of micturitions. CONCLUSION: Research findings showed the existence of three distinct categories, with a notable majority of participants belonging to the "high SPN-PCN" group. The significance of having these classes identified lies in the move away from a one-size-fits-all approach to a more nuanced understanding of care needs. Customized nursing interventions can be devised based on specific factors, such as age, education level, urinary incontinence-related symptoms and potential category. For instance, for the "high SPN-PCN" group, our nursing strategy can encompass heightened psychological support and expanded opportunities for social engagement.Furthermore, in the training and education of healthcare professionals, recognizing and meeting the needs of each potential category of older adults might require more attention. Geriatr Gerontol Int 2024; ••: ••-••.

14.
Gene ; 926: 148559, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-38740352

RESUMEN

The most prevalent glycoprotein on the influenza virus envelope is called hemagglutinin (HA), yet little is known about its involvement in the pathophysiology and etiology of severe influenza pneumonia. Here, after stimulating human bronchial epithelial cells (16-HBE) and mice with HA of H1N1 for 12 h, we investigated the proliferation, migration, inflammatory cytokines expression, and apoptosis in 16-HBE and the pathological damage in mouse lung tissue. The expression of inflammatory cytokines plasminogen activator inhibitor 1(PAI-1), urokinase-type (uPA) and tissue-type (tPA) plasminogen activators, and apoptosis were all enhanced by HA, which also prevented the proliferation and migration of bronchial epithelial cells. HA enhanced up-regulated PAI-1, uPA, and tPA protein expression within mouse lung tissue and caused lung injury. In conclusion, HA alone, but not the whole H1N1 virus, induces lung tissue injury by inhibiting cell proliferation and migration, while promoting the expression of inflammatory cytokines and apoptosis.


Asunto(s)
Apoptosis , Proliferación Celular , Glicoproteínas Hemaglutininas del Virus de la Influenza , Subtipo H1N1 del Virus de la Influenza A , Animales , Humanos , Ratones , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Movimiento Celular , Citocinas/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/virología , Pulmón/metabolismo , Pulmón/virología , Pulmón/patología , Línea Celular , Neumonía Viral/virología , Neumonía Viral/metabolismo , Neumonía Viral/patología , Gripe Humana/metabolismo , Gripe Humana/virología , Activador de Plasminógeno de Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/virología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Inhibidor 1 de Activador Plasminogénico/genética , Neumonía/metabolismo , Neumonía/virología
15.
Clin Cancer Res ; 30(9): 1878-1888, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38451195

RESUMEN

PURPOSE: Disruption of lipid bilayer asymmetry is a common feature observed in cancer cells and offers novel routes for therapeutic targeting. We used the natural immune receptor TIM-4 to interrogate for loss of plasma membrane phospholipid polarity in primary acute myelogenous leukemia (AML) samples and evaluated the anti-leukemic activity of TIM-4-L-directed T-cell therapy in preclinical AML models. EXPERIMENTAL DESIGN: We performed FACS analysis on 33 primary AML bone marrow specimens and correlated TIM-4-L expression frequency and intensity with molecular disease characteristics. Using Kasumi-1 and MV-4-11 AML cell lines, we further tested the anti-leukemic effects of TIM-4-L-directed engineered T cells in vitro and in vivo. RESULTS: We found that 86% of untreated AML blasts displayed upregulation of cell surface TIM-4-L. These observations were agnostic to AML genetic classification, as samples with mutations in TP53, ASXL1, and RUNX1 displayed TIM-4-L upregulation similar to that seen in favorable and intermediate subtypes. TIM-4-L dysregulation was also stably present in AML cell lines. To evaluate the potential of targeting upregulated TIM-4-L with adoptive T-cell therapy, we constructed TIM-4-L-directed engineered T cells, which demonstrated potent anti-leukemic effects, effectively eliminating AML cell lines with a range of endogenous TIM-4-L expression levels both in vitro and in vivo. CONCLUSIONS: These results highlight TIM-4-L as a highly prevalent target on AML across a range of genetic classifications and novel target for T-cell-based therapy in AML. Further investigations into the role of TIM-4-L in AML pathogenesis and its potential as an anti-leukemic target for clinical development are warranted.


Asunto(s)
Leucemia Mieloide Aguda , Proteínas de la Membrana , Linfocitos T , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/metabolismo , Ratones , Animales , Linfocitos T/inmunología , Linfocitos T/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Inmunoterapia Adoptiva/métodos
16.
Arch Microbiol ; 195(9): 655-60, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23912616

RESUMEN

Enterococcus sp. 812, isolated from fresh broccoli, was previously found to produce a bacteriocin active against a number of Gram-positive bacteria, including Listeria monocytogenes. Bacteriocin activity decreased slightly after autoclaving (121 °C for 15 min), but was inactivated by protease K. Mass spectrometry analysis revealed the bacteriocin mass to be approximately 4,521.34 Da. N-terminal amino acid sequencing yielded a partial sequence, NH2-ATYYGNGVYXDKKKXWVEWGQA, by Edman degradation, which contained the consensus class IIa bacteriocin motif YGNGV in the N-terminal region. The obtained partial sequence showed high homology with some enterococcal bacteriocins; however, no identical peptide or protein was found. This peptide was therefore considered to be a novel bacteriocin produced by Enterococcus sp. 812 and was termed enterocin T.


Asunto(s)
Bacteriocinas/aislamiento & purificación , Bacteriocinas/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Bacteriocinas/química , Enterococcus/química , Enterococcus/metabolismo , Bacterias Grampositivas , Alineación de Secuencia
17.
Lipids Health Dis ; 12: 186, 2013 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-24341743

RESUMEN

BACKGROUND: Apolipoprotein O (apoO) is a new member of the apolipoprotein family. However, data on its physiological functions are limited and inconsistent. Using a microarray expression analysis, this study explored the function of apoO in liver cells. METHODS: HepG2 cells were treated either with oleic acid or tumor necrosis factor-α for 24 h. mRNA and protein expression of apoO were assessed by quantitative real-time PCR (qRT-PCR) and Western blot respectively. An efficient lentiviral siRNA vector targeting the human apoO gene was designed and constructed. The gene expression profile of HepG2 human hepatocellular carcinoma cells transfected with the apoO silencing vector was investigated using a whole-genome oligonucleotide microarray. The expression levels of some altered genes were validated using qRT-PCR. RESULTS: ApoO expression in HepG2 cells was dramatically affected by lipid and inflammatory stimuli. A total of 282 differentially expressed genes in apoO-silenced HepG2 cells were identified by microarray analysis. These genes included those participating in fatty acid metabolism, such as ACSL4, RGS16, CROT and CYP4F11, and genes participating in the inflammatory response, such as NFKBIZ, TNFSF15, USP2, IL-17, CCL23, NOTCH2, APH-1B and N2N. The gene Uncoupling protein 2 (UCP2), which is involved in both these metabolic pathways, demonstrated significant changes in mRNA level after transfection. CONCLUSIONS: It is likely that apoO participates in fatty acid metabolism and the inflammatory response in HepG2 cells, and UCP2 may act as a mediator between lipid metabolism and inflammation in apoO-silenced HepG2 cells.


Asunto(s)
Apolipoproteínas/genética , Canales Iónicos/genética , Proteínas Mitocondriales/genética , Ácido Oléico/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Apolipoproteínas/antagonistas & inhibidores , Apolipoproteínas/metabolismo , Ácidos Grasos/metabolismo , Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica , Células Hep G2 , Humanos , Inflamación/genética , Canales Iónicos/metabolismo , Metabolismo de los Lípidos/genética , Análisis por Micromatrices , Proteínas Mitocondriales/metabolismo , Anotación de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proteína Desacopladora 2
18.
J Sci Food Agric ; 93(1): 166-72, 2013 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-22696120

RESUMEN

BACKGROUND: Echinacea purpurea L. (EP) is a popular herbal antioxidant and immunomodulator. The present study was conducted to evaluate the effects of EP on meat quality and oxidative status in broilers. Two hundred and fifty (1-day-old) male broilers (Arbor Acres) were randomly allocated to five groups including the control (corn-soybean meal diet) and 0.1, 0.5, 1.0 and 2.0% EP powder groups, with two replicates per treatment group. RESULTS: The results indicated that the addition of 0.5% and 1.0% EP significantly increased water-holding capacity and decreased storage loss of breast and thigh fillets at 35 days old. For fillet colour, L* (lightness) values were lower, and a* (redness) and b* (yellowness) values were higher with EP supplementation. Lower crude fat contents were observed in EP groups in comparison with control at 35 days of age in breast and thigh fillets, respectively. Production of malondialdehyde was slightly reduced in serum of EP supplemented birds compared to the control group. Results for Trolox equivalent antioxidant capacity, catalase and superoxide dismutase were significantly higher for the 0.5, 1.0 and 2.0% EP supplemental groups than control group in serum. Liver and spleen tissues results showed that the antioxidative enzymes activities were higher with EP powder at 35 days of age. CONCLUSION: Dried EP can be used as a feed additive to improve the meat quality and oxidative status in Arbor Acres broilers.


Asunto(s)
Antioxidantes/farmacología , Color , Suplementos Dietéticos , Echinacea , Peroxidación de Lípido/efectos de los fármacos , Carne/análisis , Preparaciones de Plantas/farmacología , Animales , Antioxidantes/metabolismo , Catalasa/sangre , Pollos , Grasas de la Dieta/análisis , Humanos , Hígado/metabolismo , Malondialdehído/sangre , Carne/normas , Bazo/metabolismo , Superóxido Dismutasa/metabolismo , Agua
19.
Artículo en Zh | MEDLINE | ID: mdl-24148961

RESUMEN

OBJECTIVE: To study the occupational exposure limit of dimethoxymethane (DMM) in workplace air. METHODS: Literature research was conducted on DMM; information on its physicochemical properties, toxicology, and occupational epidemiology was collected. Upon analyzing these data, an occupational exposure limit of DMM in workplace air was proposed according to the guidelines and principles of developing occupational exposure limits for harmful factors in workplaces. RESULTS: A total of 165 air samples were collected from DMM manufacturers, 14 of which had a DMM concentration over 3000 mg/m(3), accounting for 8.48% of all samples. Compared with the control group, the exposed employees had a significantly increased incidence of discomfort symptoms when exposed to more than 6000 mg/m(3) DMN (P < 0.01).No significant differences in the constituent ratios of abnormal results in physical examinations were found between the exposure groups and control group (P > 0.05). CONCLUSION: We recommend to set the permissible concentration-time weighed average to 3100 mg/m(3) as the occupational exposure limit of DMM in workplace air in China. This occupational exposure limit standard meets the relevant requirements of toxicology and occupational epidemiology, as well as fits well with our country's current economical and technological levels. This standard has high applicability in China's domestic settings.


Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Éteres Metílicos/análisis , Exposición Profesional/análisis , China , Humanos , Exposición por Inhalación , Valores Limites del Umbral , Lugar de Trabajo
20.
Am J Respir Cell Mol Biol ; 46(6): 797-806, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22281985

RESUMEN

Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2(-/-)) mice. Rats injected with a polyclonal antibody to CCL-2 showed higher levels of albumin and IL-6 in the bronchoalveolar lavage and myeloperoxidase in the lung tissue after LC. Closed-chest bilateral LC demonstrated CCL-2 localization in alveolar macrophages (AMs) and epithelial cells. Subsequent experiments performed using a murine model of LC showed that the extent of injury, assessed by pulmonary compliance and albumin levels in the bronchoalveolar lavage, was higher in the CCR2(-/-) mice when compared with the wild-type (WT) mice. We also found increased release of IL-1ß, IL-6, macrophage inflammatory protein-1, and keratinocyte chemoattractant, lower recruitment of AMs, and higher neutrophil infiltration and phagocytic activity in CCR2(-/-) mice at 24 hours. However, impaired phagocytic activity was observed at 48 hours compared with the WT. Production of CCL-2 and macrophage chemoattractant protein-5 was increased in the absence of CCR2, thus suggesting a negative feedback mechanism of regulation. Isolated AMs in the CCR2(-/-) mice showed a predominant M1 phenotype compared with the predominant M2 phenotype in WT mice. Taken together, the above results show that CCL-2 is functionally important in the down-modulation of injury and inflammation in LC.


Asunto(s)
Quimiocina CCL2/fisiología , Contusiones/fisiopatología , Inflamación/fisiopatología , Lesión Pulmonar/fisiopatología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Fagocitosis , Ratas , Ratas Long-Evans
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