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1.
Langmuir ; 40(6): 3181-3189, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38303628

RESUMEN

Hydrolyzed polyacrylamide (HPAM) is commonly used in polymer flooding, however, it is prone to viscosity reduction at high temperatures and high salinities, weakening its ability to improve oil recovery. In this work, sulfonated modified silicon quantum dots (S-SiQDs) were synthesized and then added to HPAM to study the improvement of rheological properties and enhanced oil recovery performance of HPAM at high temperatures and salinities. It is found that the S-SiQDs with a concentration of only 0.1 wt % can significantly increase the viscosity of HPAM from 28.5 to 39.6 mPa·s at 60 °C and 10,000 mg/L NaCl. Meanwhile, the HPAM/S-SiQDs hybrid solution always possessed higher viscosity and viscoelastic moduli than HPAM, attributed to the hydrogen bonding between HPAM and S-SiQDs. Notably, HPAM/S-SiQDs still maintained elastic behavior at harsh conditions, indicating that they formed a strong network structure. Through oil displacement experiments, it was found that the oil recovery of HPAM/S-SiQDs was higher (28.3%), while that of HPAM was only 17.2%. Thereafter, the utilization sequence of oil during the displacement process was studied with nuclear magnetic resonance experiments. Ultimately, the oil displacement mechanism of HPAM/S-SiQDs was deeply analyzed, including viscosity thickening and wetting reversal.

2.
Heliyon ; 9(9): e19648, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37809861

RESUMEN

Climate change is increasing the intensity of extreme climate events. Significant impacts of extreme climate events on human society and ecosystem have occurred in many places of the world, for example, Southwest China (SWC). In this study, the daily temperature and precipitation data from 438 meteorological stations are used to analyze the variation characteristics of extreme climate events in the SWC from 1961 to 2017. The annual extreme warm events show a significant increasing trend at 99% confidence level at most stations, and a few stations with a decreasing trend are mainly located in the southern Sichuan Province, the northern Yunnan Province and the western Guizhou Province. Meanwhile, the annual extreme cold events show a significant decreasing trend at 99% confidence level at most stations, and a few stations with an increasing trend are mainly distributed in the Sichuan Basin. Both the annual extreme heavy precipitation indexes and rainstorm indexes show nonsignificant increasing trends, but they differ greatly in the spatial distribution. These indexes in the western Tibet, Chongqing and most parts of Guizhou show significant increasing trends at 95% confidence level, while those in the central Sichuan and southeastern Yunnan show significant decreasing trends. The percentage of extreme heavy precipitation shows a significant increasing trend at 99% confidence level, especially in the northeastern Sichuan, the central-eastern Guizhou and the central Yunnan. Overall, under the background of global warming, the extreme warm events in SWC increase significantly from 1961 to 2017, and the extreme cold events decrease significantly. The variation trends of extreme precipitation events differ greatly in different regions, and the percentage of extreme heavy precipitation increases significantly.

3.
Gels ; 9(9)2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37754407

RESUMEN

To expand the applicability of gel fracturing fluids in ultra-high-temperature reservoirs, a temperature-resistant polymer was synthesized using the solution polymerization method. Subsequently, an ultra-high-temperature-resistant polymer gel was formulated by incorporating an organic zirconium crosslinking agent. A comprehensive investigation was carried out to systematically study and evaluate the steady shear property, dynamic viscoelasticity, and temperature and shear resistance performance, as well as the core damage characteristics of the polymer gel. The obtained results demonstrate that the viscosity remained at 147 mPa·s at a temperature of 200 °C with a shear rate of 170 s-1. Compared with the significant 30.9% average core damage rate observed in the guanidine gum fracturing fluid, the core damage attributed to the polymer gel was substantially mitigated, measuring only 16.6%. Finally, the gelation mechanism of the polymer gel was scrutinized in conjunction with microscopic morphology analysis. We expect that this study will not only contribute to the effective development of deep and ultradeep oil and gas reservoirs but also furnish a theoretical foundation for practical field applications.

4.
Cancer Commun (Lond) ; 43(8): 909-937, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37434399

RESUMEN

BACKGROUND: Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2 (HER2)-positive gastric cancer. However, the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit, and there is currently no effective reversal measure. Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves, while the understanding of the mechanisms of environment-mediated drug resistance is relatively lacking. This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients. METHODS: Trastuzumab-sensitive and trastuzumab-resistant HER2-positive tumor tissues and cells were collected for transcriptome sequencing. Bioinformatics were used to analyze cell subtypes, metabolic pathways, and molecular signaling pathways. Changes in microenvironmental indicators (such as macrophage, angiogenesis, and metabolism) were verified by immunofluorescence (IF) and immunohistochemical (IHC) analyses. Finally, a multi-scale agent-based model (ABM) was constructed. The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM. RESULTS: Based on transcriptome sequencing, molecular biology, and in vivo experiments, we found that the level of glutamine metabolism in trastuzumab-resistant HER2-positive cells was increased, and glutaminase 1 (GLS1) was significantly overexpressed. Meanwhile, tumor-derived GLS1 microvesicles drove M2 macrophage polarization. Furthermore, angiogenesis promoted trastuzumab resistance. IHC showed high glutamine metabolism, M2 macrophage polarization, and angiogenesis in trastuzumab-resistant HER2-positive tumor tissues from patients and nude mice. Mechanistically, the cell division cycle 42 (CDC42) promoted GLS1 expression in tumor cells by activating nuclear factor kappa-B (NF-κB) p65 and drove GLS1 microvesicle secretion through IQ motif-containing GTPase-activating protein 1 (IQGAP1). Based on the ABM and in vivo experiments, we confirmed that the combination of anti-glutamine metabolism, anti-angiogenesis, and pro-M1 polarization therapy had the best effect in reversing trastuzumab resistance in HER2-positive gastric cancer. CONCLUSIONS: This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism, M2 macrophage polarization, and pro-angiogenic function of macrophages, leading to acquired trastuzumab resistance in HER2-positive gastric cancer. A combination of anti-glutamine metabolism, anti-angiogenesis, and pro-M1 polarization therapy may provide a new insight into reversing trastuzumab resistance.


Asunto(s)
Glutamina , Neoplasias Gástricas , Animales , Ratones , Humanos , Trastuzumab/farmacología , Trastuzumab/uso terapéutico , Ratones Desnudos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Resistencia a Antineoplásicos , Macrófagos/metabolismo , Microambiente Tumoral
5.
J Psychol ; 157(1): 32-47, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36279261

RESUMEN

The present study tested the mediating role of self-esteem and the moderating role of mindfulness in the association between upward social comparison on social network sites (SNSs) and adolescent materialism. A sample of 880 Chinese adolescents completed measures of upward social comparison on SNSs, materialism, self-esteem, mindfulness, and demographic information. Results showed that self-esteem mediated the link between upward social comparison on SNSs and adolescent materialism. That is, upward social comparison on SNSs was positively associated with adolescent materialism through the decreased self-esteem. Moreover, mindfulness acted as an important moderator in the mediation model. Both the direct association between upward social comparison on SNSs and materialism and the indirect association via self-esteem were moderated by mindfulness. These two associations were both weaker for adolescents with higher mindfulness than for those with lower mindfulness. These findings would advance our understanding of how and when upward social comparison on SNSs is associated with adolescent materialism. Limitations and implications of the present study are discussed.


Asunto(s)
Atención Plena , Adolescente , Humanos , Comparación Social , Autoimagen , Pueblo Asiatico
6.
Amino Acids ; 54(11): 1437-1450, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36224443

RESUMEN

2-Pyrrolidone is widely used in the textile and pharmaceutical industries. Here, we established a 2-pyrrolidone biosynthesis pathway in Corynebacterium glutamicum, by expressing glutamate decarboxylase (Gad) mutant and ß-alanine CoA transferase (Act) which activates spontaneous dehydration cyclization of GABA to form 2-pyrrolidone. Also, the 5' untranslated regions (UTR) strategy was used to increase the expression of protein. Furthermore, considering the importance of acetyl-CoA in the 2-pyrrolidone synthesis pathway, the acetyl-CoA synthetase (acsA) gene was introduced to convert acetate into acetyl-CoA thus achieving the recyclability of the economy. Finally, the fed-batch fermentation of the final strain in a 5 L bioreactor produced 10.5 g/L 2-pyrrolidone within 78 h, which increased by 42.5% by altering the level of gene expression. This is the first time to build the basic chemical 2-pyrrolidone from glucose in one step in C. glutamicum.


Asunto(s)
Corynebacterium glutamicum , Corynebacterium glutamicum/metabolismo , Vías Biosintéticas , Acetilcoenzima A/metabolismo , Ingeniería Metabólica
7.
Cancer Res ; 82(8): 1503-1517, 2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35255118

RESUMEN

Trastuzumab is the only approved targeted drug for first-line treatment of HER2-positive advanced gastric cancer, but the high rate of primary resistance and rapid emergence of secondary resistance limit its clinical benefits. We found that trastuzumab-resistant (TR) gastric cancer cells exhibited high glycolytic activity, which was controlled by hexokinase 2 (HK2)-dependent glycolysis with a circadian pattern [higher at zeitgeber time (ZT) 6, lower at ZT18]. Mechanistically, HK2 circadian oscillation was regulated by a transcriptional complex composed of PPARγ and the core clock gene PER1. In vivo and in vitro experiments demonstrated that silencing PER1 disrupted the circadian rhythm of PER1-HK2 and reversed trastuzumab resistance. Moreover, metformin, which inhibits glycolysis and PER1, combined with trastuzumab at ZT6, significantly improved trastuzumab efficacy in gastric cancer. Collectively, these data introduce the circadian clock into trastuzumab therapy and propose a potentially effective chronotherapy strategy to reverse trastuzumab resistance in gastric cancer. SIGNIFICANCE: In trastuzumab-resistant HER2-positive gastric cancer, glycolysis fluctuates with a circadian oscillation regulated by the BMAL1-CLOCK-PER1-HK2 axis, which can be disrupted with a metformin-based chronotherapy to overcome trastuzumab resistance.


Asunto(s)
Hexoquinasa , Metformina , Proteínas Circadianas Period , Neoplasias Gástricas , Ritmo Circadiano/genética , Hexoquinasa/genética , Humanos , Proteínas Circadianas Period/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Trastuzumab/farmacología , Trastuzumab/uso terapéutico
8.
Cancer Immunol Res ; 10(2): 182-199, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34933913

RESUMEN

Metastatic microsatellite-stable (MSS) colorectal cancer rarely responds to immune checkpoint inhibitors (ICI). Metabolism heterogeneity in the tumor microenvironment (TME) presents obstacles to antitumor immune response. Combining transcriptome (The Cancer Genome Atlas MSS colorectal cancer, n = 383) and digital pathology (n = 96) analysis, we demonstrated a stroma metabolism-immune excluded subtype with poor prognosis in MSS colorectal cancer, which could be attributed to interaction between chondroitin-6-sulfate (C-6-S) metabolites and M2 macrophages, forming the "exclusion barrier" in the invasive margin. Furthermore, C-6-S derived from cancer-associated fibroblasts promoted co-nuclear translocation of pSTAT3 and GLI1, activating the JAK/STAT3 and Hedgehog pathways. In vivo experiments with C-6-S-targeted strategies decreased M2 macrophages and reprogrammed the immunosuppressive TME, leading to enhanced response to anti-PD-1 in MSS colorectal cancer. Therefore, C-6-S-induced immune exclusion represents an "immunometabolic checkpoint" that can be exploited for the application of combination strategies in MSS colorectal cancer ICI treatment.


Asunto(s)
Sulfatos de Condroitina , Neoplasias Colorrectales , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Proteínas Hedgehog/genética , Humanos , Repeticiones de Microsatélite , Sulfatos , Microambiente Tumoral
9.
ACS Synth Biol ; 9(7): 1855-1863, 2020 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-32551572

RESUMEN

l-Proline takes a significant role in the pharmaceutical and chemical industries as well as graziery. Typical biosynthesis of l-proline is from l-glutamate, involving three enzyme reactions as well as a spontaneous cyclization. Alternatively, l-proline can be also synthesized in l-ornithine and/or l-arginine producing strains by an ornithine aminotransferase (OCD). In this study, a strategy of directed evolution combining rare codon selection and pEvolvR was developed to screen OCD with high catalytic efficiency, improving l-proline production from l-arginine chassis cells. The mutations were generated by CRISPR-assisted DNA polymerases and were screened by growth-coupled rare codon selection system. OCDK205G/M86K/T162A from Pseudomonas putida was identified with 2.85-fold increase in catalytic efficiency for the synthesis of l-proline. Furthermore, we designed and optimized RBS for the BaargI and Ppocd coupling cascade using RedLibs, as well as sRNA inhibition of argF to moderate l-proline biosynthesis in l-arginine overproducing Corynebacterium crenatum. The strain PS6 with best performance reached 15.3 g/L l-proline in the shake flask and showed a titer of 38.4 g/L in a 5 L fermenter with relatively low concentration of residual l-ornithine and/or l-arginine.


Asunto(s)
Corynebacterium/enzimología , Corynebacterium/genética , Evolución Molecular Dirigida/métodos , Ornitina-Oxo-Ácido Transaminasa/metabolismo , Prolina/biosíntesis , Pseudomonas putida/enzimología , Pseudomonas putida/genética , Amoníaco-Liasas , Arginina/biosíntesis , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biocatálisis , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Codón , ADN Polimerasa Dirigida por ADN , Ingeniería Metabólica/métodos , Proteínas Mutantes/metabolismo , Mutación , Ornitina/biosíntesis , Ornitina-Oxo-Ácido Transaminasa/genética , Plásmidos/genética
10.
Sci Adv ; 6(21): eaba2383, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32494747

RESUMEN

Trans-4-hydroxy-l-proline is produced by trans-proline-4-hydroxylase with l-proline through glucose fermentation. Here, we designed a thorough "from A to Z" strategy to significantly improve trans-4-hydroxy-l-proline production. Through rare codon selected evolution, Escherichia coli M1 produced 18.2 g L-1 l-proline. Metabolically engineered M6 with the deletion of putA, proP, putP, and aceA, and proB mutation focused carbon flux to l-proline and released its feedback inhibition. It produced 15.7 g L-1 trans-4-hydroxy-l-proline with 10 g L-1 l-proline retained. Furthermore, a tunable circuit based on quorum sensing attenuated l-proline hydroxylation flux, resulting in 43.2 g L-1 trans-4-hydroxy-l-proline with 4.3 g L-1 l-proline retained. Finally, rationally designed l-proline hydroxylase gave 54.8 g L-1 trans-4-hydroxy-l-proline in 60 hours almost without l-proline remaining-the highest production to date. The de novo engineering carbon flux through rare codon selected evolution, dynamic precursor modulation, and metabolic engineering provides a good technological platform for efficient hydroxyl amino acid synthesis.

11.
Huan Jing Ke Xue ; 40(9): 3886-3897, 2019 Sep 08.
Artículo en Chino | MEDLINE | ID: mdl-31854850

RESUMEN

Based on the latest monthly data of moderate resolution imaging spectroradiometer (MODIS)/Terra C6.1 aerosol optical depth (AOD), the temporal-spatial distribution and variability trend in AOD over China during 2001-2017 are analyzed to explore the distribution and variation characteristics of AOD in China. Regarding the spatial characteristics, the first prominent high-value center of the annual mean AOD was located in the industrially and economically developed areas of the North China Plain, Central China, the Yangtze River Delta region, the Pearl River Delta region, and the Sichuan Basin. The second prominent high-value center of the annual mean AOD was located in the dust aerosol-dominated areas of Taklimakan Desert. Two low-value centers of the annual mean AOD were located in the eastern part of Inner Mongolia to the north of Northeast China and the Tibet Plateau. Regarding the temporal characteristics, the AOD value peaked in eight areas in spring and summer. The annual mean AOD values in the Taklimakan Desert, Sichuan Basin, and Pearl River Delta peaked from March to May, and those in the North China Plain, Central China, and Yangtze River Delta peaked from May to July. The trend characteristics showed that during 2001-2006, the AOD in Northwest China and Inner Mongolia showed a downtrend, and that in the east-central China and the eastern part of southwest China showed a growth trend. During 2007-2012, the trend of AOD in the Tibetan Plateau and the Taklimakan Desert changed from decreasing to increasing. The growth trend of AOD in the North China Plain and the Sichuan Basin was weakened, and the AOD in the Yangtze River Delta showed a weak downward trend. During 2013-2017, the AOD in most areas of China showed a significant downward trend.

12.
Sci Total Environ ; 657: 498-508, 2019 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-30550913

RESUMEN

The alpine wetlands on the Tibetan Plateau (TP) are ecosystems vulnerable to global climate change. It has been recognized that future climate change may have a significant impact on methane (CH4) emissions from the plateau, while less attention has been paid to predicting temporal and spatial variations in CH4 emissions from TP natural wetlands. In this study, we used an integrated model framework based on the CH4MODwetland, TOPMODEL and TEM models to predict CH4 emissions from potential natural wetlands on the TP under IPCC AR5 scenarios from 2006 to 2100. The model estimates suggest that the mean area-weighted CH4 fluxes will increase from 4.45 ±â€¯0.42 g m-2 yr-1 in 2006 to 4.79 ±â€¯0.72, 5.99 ±â€¯0.85 and 11.53 ±â€¯1.33 g m-2 yr-1 under 3 Representative Concentration Pathway scenarios (RCP 2.6, RCP 4.5 and RCP 8.5 scenarios), respectively, by 2100. The dominant drivers stimulating CH4 emissions are air temperature, precipitation and net primary productivity (NPP). Spatially, CH4 fluxes and emissions showed a decreasing trend from south to north and from east to west. In response to climate change, a total of 0.42 ±â€¯0.06, 0.54 ±â€¯0.09 and 1.01 ±â€¯0.12 Tg yr-1 of CH4 emissions will be emitted from the TP's potential natural wetlands by the end of this century under the RCP 2.6, RCP 4.5 and RCP 8.5 scenarios, respectively.

13.
Games Health J ; 4(3): 202-10, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26182065

RESUMEN

OBJECTIVE: This four-stage study culminated in a game interface designed to calibrate people's perceptions of net risk (combining frequency and severity), in contexts where risks are elevated from their accepted, "typical" values, as when avalanche threats elevate the risks of "skiing" above levels skiers normally accept. Risk prompts are displayed dynamically, in naturalistic language, and not, for example, as static displays of dollar amounts or probabilities. Individual differences are measured. MATERIALS AND METHODS: In Stage 1 (pilot), focus groups (n=9) piloted procedures, visual prompts, and examples of contexts where risks elevated from the "usual," for use in upcoming stages. In Stage 2 (exploratory), participants (primarily students; n=119; mean age, 20.1 years; 64 percent male) were assigned to risk contexts, answered demographic and risk-history questions, and then matched risk-description prompts to perceived "appropriate" levels along an ordinal risk scale. Descriptive measures and graphs showed response distributions; chi-squared analyses compared responses for different demographics. In Stage 3 (manipulating "cards"), participants (n=80; mean age, 37 years; 60 percent male) matched naturalistic risk prompts with ordinal risk positions. Regressions compared cards' placements with their "expected" (per exploratory Stage 2) placements. In Stage 4, the interface was coded in the Unity(®) (implemented at Business and IT Capstone, University of Ontario Institute of Technology, Oshawa, ON, Canada) development environment. RESULTS: In Stage 1, ambiguities in draft wordings/displays for Stage 2 were identified and corrected. Three risk contexts emerged: traffic/hidden intersection; skiing/avalanche; and swimming/drowning. In Stage 2, for traffic and skiing contexts, responses relating ordinal risk categories to realistic examples were observed to cluster around values potentially usable as markers. No associations appeared with demographic variables. In Stage 3, actual and "expected" ordinal-risk-category assignments for naturalistic risk markers were well correlated. "Approximate mappings" between markers and categories appeared stable. In Stage 4, the interface design incorporated the "approximate mappings"-yet also incorporated a "tuning phase," for measuring and recording individual differences. CONCLUSIONS: The interface can capture individual differences in risk perception on two key dimensions (frequency and severity)-viewed in dynamic, naturalistic scenarios, where risk levels are increased.


Asunto(s)
Percepción , Medición de Riesgo , Interfaz Usuario-Computador , Juegos de Video , Adulto , Conducción de Automóvil/psicología , Toma de Decisiones , Femenino , Juegos Recreacionales , Humanos , Masculino , Recreación/psicología , Riesgo , Asunción de Riesgos , Esquí/psicología , Natación/psicología , Adulto Joven
14.
Zhonghua Yi Xue Za Zhi ; 94(26): 2004-7, 2014 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-25312658

RESUMEN

OBJECTIVE: To explore the expression levels and roles of Krüpple-like factor 5 (KLF5) in tumor necrosis factor α (TNFα)-induced SK-BR-3 breast cancer cells. METHODS: SK-BR-3 breast cancer cells were stimulated by TNFα at different concentrations (0, 1, 5, 10, 20 µg/L) for specified durations (0, 6, 12, 24, 36 h). Western blot was performed to detect KLF5 protein levels. Then Western blot and quantitative real-time PCR (qRT-PCR) were used to detect the expression levels of apoptosis genes. Flow cytometry and qRT-PCR were used to observe the effects of exogenous KLF5 on TNFα-induced apoptosis of SK-BR-3 breast cancer cell. RESULTS: KLF5 expression levels significantly decreased in TNFα-stimulated SK-BR-3 breast cancer cells in a concentration- and time-dependent manner. Quantitative RT-PCR results showed that TNFα up-regulate apoptosis gene caspase 3, caspase 9 and bax expression levels and down-regulate bcl-1 level in SK-BR-3 cells. Adenovirus expression vectors of pAd-GFP and pAd-GFP-KLF5 were constructed and used to infect SK-BR-3 breast cancer cells. Over-expression of GFP-KLF5 inhibited apoptosis in TNFα-stimulated SK-BR-3 breast cancer cells. CONCLUSION: TNFα reduces KLF5 expression in SK-BR-3 breast cancer cells and KLF5 participates in TNFα-induced SK-BR-3 cell apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Factores de Transcripción de Tipo Kruppel/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/farmacología , Línea Celular Tumoral , Humanos
15.
Chin Med J (Engl) ; 127(7): 1328-33, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24709189

RESUMEN

BACKGROUND: Adoptive cell transfer (ACT) immunotherapy has been used clinically for years to treat malignancies. Improving the killing efficiency of effector cells, such as tumor-specific cytotoxic T lymphocytes (CTLs), is an important component for enhancing the clinical response of cancer immunotherapy. Hence, we explored a novel method for preparing cancer-specific CTLs using naive T lymphocytes. METHODS: C57BL/6 mice bearing B16 melanoma tumors were pretreated with cyclophosphamide (CTX) by peritoneal injection. The immunosuppressive influence of CTX on tumor regression and the tumor microenvironment was assessed. Naive T cells and T cell pools were isolated via negative selection using immunomagnetic beads. The proliferative potential and cytokine production of different T cell subpopulations were evaluated in vitro. Tumor-specific CTLs derived from naive T cells (naive CD4+ T cells: naive CD8+ T cells = 2:1) and pooled T cells were generated in vitro, respectively. B16 melanoma-bearing C57BL/6 mice were pretreated with CTX, followed by ACT immunotherapy using dendritic cell-induced CTLs. The homing abilities of the effector cells and interleukin-2 (IL-2), interferon-γ, granzyme B, and perforin mRNA levels in tumor tissues were evaluated, and the change in tumor volume was measured. RESULTS: Mice receiving CTX peritoneal pretreatment injections did not display tumor regression compared with control mice. However, a significant downregulation of splenic Tregs and tumor growth factor-ß1 (TGF-ß1) and interleukin-10 (IL-10) serum levels was observed (P < 0.05). Naive T cells showed a stronger proliferative capacity and elevated cytokine production than did pooled T cells (P < 0.05). In addition, effector cells generated from naive T cells displayed more potent antitumor activity in vivo than those derived from pooled T cells (P < 0.05). CONCLUSION: Effector cells derived from the naive T cells possess a stronger proliferative potential, homing capacity, and enhanced cytokine production, which leads to a superior antitumor response.


Asunto(s)
Inmunoterapia Adoptiva/métodos , Melanoma Experimental/terapia , Animales , Línea Celular Tumoral , Células Cultivadas , Femenino , Citometría de Flujo , Ratones Endogámicos C57BL
16.
Zhonghua Yi Xue Za Zhi ; 93(30): 2385-7, 2013 Aug 13.
Artículo en Chino | MEDLINE | ID: mdl-24300208

RESUMEN

OBJECTIVE: To explore the effects of low-dose radiation on the expression of immunogenic membrane molecules calreticulin (CRT) and MHC-I/II on the surface of human renal clear cell carcinoma 786-0 cells. METHODS: The inhibitory activity of low-dose radiation on cell line 786-0 was examined by CCK-8 assay. And the post-radiation membrane expressions of CRT, MHC-I and MHC-II were measured by flow cytometry while CRT was visualized by immunofluorescence photography. RESULTS: The inhibition rates on the proliferative capacities of four 786-0 cell lines rose with the incremental radiation doses of 0, 6, 12 and 24 Gy. And the CRT expression levels of each experimental group was significantly higher than that of the control group (P < 0.001). Along with incremental doses of irradiation, the average calreticulin fluorescence intensities increased gradually initially and then there was a downward trend. The membrane expressions of MHC-I and MHC-II of each experimental group was significantly higher than those of the control group (P < 0.05). As the irradiation dose increased, the average MHC-I fluorescence intensities increased gradually in a dose-dependent manner. CONCLUSION: The low-dose radiotherapy may up-regulate CRT and MHC class I/II related with the immunogenicity of tumor cells to induce immune response against tumors.


Asunto(s)
Calreticulina/genética , Carcinoma de Células Renales/inmunología , Genes MHC Clase II/genética , Genes MHC Clase I/genética , Calreticulina/metabolismo , Humanos , Dosificación Radioterapéutica , Células Tumorales Cultivadas/inmunología , Células Tumorales Cultivadas/efectos de la radiación
17.
Chin Med J (Engl) ; 125(5): 794-800, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22490577

RESUMEN

BACKGROUND: Adoptive transfer of allogeneic tumor-specific T cells often results in severe graft-versus-host disease (GVHD). Here, we sought to maximize graft-versus-tumor and minimize GVHD by using haploidentical T cells in pre-irradiated B16-melanoma bearing mice. METHODS: C57BL/6 mice bearing B16-melanoma tumors were irradiated with 0, 5, or 7 Gy total body irradiation (TBI), or 7 Gy TBI plus bone marrow transplantation. Tumor areas were measured every 3 days to assess the influence of irradiation treatment on tumor regression. B16-melanoma bearing mice were irradiated with 7 Gy TBI; sera and spleens were harvested at days 1, 3, 5, 7, 9, 11, and 13 after irradiation. White blood cell levels were measured and transforming growth factor ß1 (TGF-b1) and interleukin 10 (IL-10) levels in serum were detected using enzyme-linked immunosorbent assay (ELISA) kits. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry were performed to test TGF-b1, IL-10 and Foxp3 mRNA levels and the proportion of CD4+CD25+Foxp3+ T-regulatory cells (Tregs) in spleens. B16-melanoma bearing C57BL/6 mice were irradiated with 7 Gy TBI followed by syngeneic (Syn1/Syn2) or haploidentical (Hap1/Hap2), dendritic cell-induced cytotoxic T lymphocytes (DC-CTLs) treatment, tumor areas and system GVHD were observed every 3 days. Mice were killed 21 days after the DC-CTLs adoptive transfer; histologic analyses of eyes, skin, liver, lungs, and intestine were then performed. RESULTS: Irradiation with 7 Gy TBI on the B16-melanoma-bearing mice did not influence tumor regression compared to the control group; however, it down-regulated the proportion of Tregs in spleens and the TGF-b1 and IL-10 levels in sera and spleens, suggesting inhibition of autoimmunity and intervention of tumor microenvironment. Adoptive transfer of haploidentical DC-CTLs significantly inhibited B16-melanoma growth. GVHD assessment and histology analysis showed no significant difference among the groups. CONCLUSION: Adoptive transfer of haploidentical tumor-specific T cells in irradiation-pretreated B16-melanoma bearing mice preserved antitumor capacity without causing a GVHD response.


Asunto(s)
Melanoma Experimental/terapia , Linfocitos T/inmunología , Animales , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Enfermedad Injerto contra Huésped , Inmunoterapia Adoptiva/métodos , Masculino , Melanoma Experimental/metabolismo , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena en Tiempo Real de la Polimerasa , Linfocitos T Reguladores/inmunología
18.
Zhonghua Yi Xue Za Zhi ; 90(36): 2545-8, 2010 Sep 28.
Artículo en Chino | MEDLINE | ID: mdl-21092460

RESUMEN

OBJECTIVE: to analyze the relationship between the expression of SM22α and the lymph node (LN) metastasis of breast cancer and to investigate its molecular mechanisms. METHODS: reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the expression of SM22α in breast cancer tissue and adjacent normal breast tissue. RT-PCR and Western blot were employed to investigate the SM22α mRNA and protein level in tissues of breast fibroadenoma, breast cancer without LN metastasis and breast cancer with LN metastasis. RT-PCR and zymography were used to detect the MMP2 and MMP9 expression and activity and TIMP1 expression level in breast fibroadenoma, breast cancer samples without LN metastasis and those with LN metastasis respectively. RESULTS: the expression level of SM22α mRNA in breast cancer was significantly lower than that in breast fibroadenoma or adjacent normal breast tissue (5.1% ± 2.4% vs 15.1% ± 5.3% vs 30.1% ± 5.1%, P < 0.01). The protein and mRNA expression level of SM22α in breast cancer samples with LN metastasis were significant lower than those of breast cancer without LN metastasis (6.2% ± 3.1% vs 10.1% ± 4.1%, P < 0.01). Both the expression and activity of MMP2 and MMP9 in breast cancer samples with LN metastasis were significant higher than those without LN metastasis (P < 0.01). A strong negative correlation was found between SM22α protein level and MMP2 activity (r = -0.848; n = 27; P < 0.01) or MMP9 activity (r = -0.916; n = 27; P < 0.01) in breast cancer tissue. CONCLUSION: a down-regulation of SM22α in breast cancer is correlated with LN metastasis. SM22α may inhibit the LN metastasis through a negative regulation of MMP2 and MMP9 in breast cancer.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Metástasis Linfática/patología , Proteínas de Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ganglios Linfáticos/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Pronóstico , ARN Mensajero/genética
19.
Gerontologist ; 48(5): 603-11, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18981277

RESUMEN

PURPOSE: This study evaluated the social facilitation of elderly patients' food intake beyond the presence of mealtime companions by assessing various relationships. The study examined the relationships between patients' intake and (a) the number of interpersonal exchanges with mealtime fellows, (b) the nature of behaviors expressed by the patients themselves and their fellows, and (c) the degree of complementarity between these. DESIGN AND METHODS: Interpersonal exchanges and intake were observed on repeated mealtime occasions (n = 1,477) nested within 32 geriatric patients (21 women, 11 men; age, M = 78.8 years). Participants' intake was estimated from plate leftovers. Interpersonal behaviors were examined for both participants and patients with whom they interacted in terms of agency and communion dimensions, following the interpersonal circumplex model of human interaction. With the use of multilevel regression analyses, the number, nature, and complementarity of behaviors that participants engaged in and were exposed to on a given meal were computed to test their impact on intake. RESULTS: The total amount of interaction between patients was positively related to intake. The effect was significant for both participants' own behaviors and those to which they were exposed, and it varied with the nature of the interaction; effects were significant in terms of frequency and complementarity for communal behaviors, and complementarity only for agentic behaviors. Effects could only partly be explained by meal duration effects. IMPLICATIONS: The results provide support for the effect of the number, nature, and complementarity of mealtime interpersonal behaviors on the food intake of elderly patients, and they may inspire new approaches to ensure adequate intake in this malnutrition-prone population.


Asunto(s)
Ingestión de Alimentos , Hospitalización , Relaciones Interpersonales , Anciano , Anciano de 80 o más Años , Canadá , Femenino , Humanos , Masculino , Observación , Instituciones Residenciales
20.
Can J Nurs Res ; 39(1): 98-115, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17450707

RESUMEN

It is proposed that computers could be used to examine patients' subjective experience in the face of cancer threat. This study provides initial validation of a computer-based stress task by examining the psychological, autonomic, and endocrine aspects of an individual's subjective experience of cancer threat surrounding mammography screening. A repeated measures design was used. A total of 38 healthy women performed a stress task (pertaining to mammography) and a control task (pertaining to osteoporosis prevention) on separate days during which psychological, autonomic, and endocrine reactions were monitored. Compared with the control task, the stress task induced higher autonomic responses (skin conductance and heart rate variability) and endocrine responses (salivary cortisol) but not psychological distress. Further, both the autonomic (skin conductance) and endocrine responses to cancer threat were moderated by mastery, a trait known to have a stress-buffering effect. Yet such a moderating effect was not observed for psychological indices of stress--that is, mood. Implications for nursing research and interventions are discussed.


Asunto(s)
Síntomas Afectivos , Neoplasias de la Mama/psicología , Hidrocortisona/metabolismo , Imágenes en Psicoterapia , Estrés Psicológico/psicología , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/enfermería , Femenino , Humanos , Mamografía/psicología , Persona de Mediana Edad , Sistemas Neurosecretores/fisiología , Saliva/metabolismo , Estrés Psicológico/enfermería , Estrés Psicológico/fisiopatología
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