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1.
BMC Musculoskelet Disord ; 25(1): 455, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851675

RESUMEN

BACKGROUND: Masquelet membrane induction technology is one of the treatment strategies for large bone defect (LBD). However, the angiogenesis ability of induced membrane decreases with time and autologous bone grafting is associated with donor site morbidity. This study investigates if the PRP-FG-nHA/PA66 scaffold can be used as a spacer instead of PMMA to improve the angiogenesis ability of induced membrane and reduce the amount of autologous bone graft. METHODS: Platelet rich plasma (PRP) was prepared and PRP-FG-nHA/PA66 scaffold was synthesized and observed. The sustained release of VEGFA and porosity of the scaffold were analyzed. We established a femur LBD model in male SD rats. 55 rats were randomly divided into four groups depending on the spacer filled in the defect area. "Defect only" group (n = 10), "PMMA" group (n = 15), "PRP-nHA/PA66" group (n = 15) and "PRP-FG-nHA/PA66" group (n = 15 ). At 6 weeks, the spacers were removed and the defects were grafted. The induced membrane and bone were collected and stained. The bone formation was detected by micro-CT and the callus union was scored on a three point system. RESULTS: The PRP-FG-nHA/PA66 scaffold was porosity and could maintain a high concentration of VEGFA after 30 days of preparation. The induced membrane in PRP-FG-nHA/PA66 group was thinner than PMMA, but the vessel density was higher.The weight of autogenous bone grafted in PRP-FG-nHA/PA66 group was significantly smaller than that of PMMA group. In PRP-FG-nHA/PA66 group, the bone defect was morphologically repaired. CONCLUSION: The study showed that PRP-FG-nHA/PA66 scaffold can significantly reduce the amount of autologous bone graft, and can achieve similar bone defect repair effect as PMMA. Our findings provide some reference and theoretical support for the treatment of large segmental bone defects in humans.


Asunto(s)
Fémur , Plasma Rico en Plaquetas , Ratas Sprague-Dawley , Andamios del Tejido , Animales , Masculino , Ratas , Fémur/cirugía , Fémur/patología , Factor A de Crecimiento Endotelial Vascular , Regeneración Ósea/fisiología , Neovascularización Fisiológica , Trasplante Óseo/métodos , Durapatita/química , Modelos Animales de Enfermedad , Osteogénesis/fisiología
2.
Materials (Basel) ; 16(17)2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37687469

RESUMEN

With the advancement in computational approaches and experimental, simulation, and modeling tools in recent decades, a trial-and-validation method is attracting more attention in the materials community. The development of powder metallurgy Ni-based superalloys is a vivid example that relies on simulation and experiments to produce desired microstructure and properties in a tightly controlled manner. In this research, we show an integrated approach to predicting the grain size of industrial forgings starting from lab-scale cylindrical compression by employing modeling and experimental validation. (a) Cylindrical compression tests to obtain accurate flow stress data and the hot working processing window; (b) double-cone tests of laboratory scale validation; (c) sub-scale forgings for further validation under production conditions; and (d) application and validation on full-scale industrial forgings. The procedure uses modeling and simulation to predict metal flow, strain, strain rate, temperature, and the resulting grain size as a function of thermo-mechanical processing conditions. The models are calibrated with experimental data until the accuracy of the modeling predictions is at an acceptable level, which is defined as the accuracy at which the results can be used to design and evaluate industrial forgings.

3.
Insights Imaging ; 14(1): 68, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37093321

RESUMEN

BACKGROUND: To develop an artificial intelligence (AI) model with radiomics and deep learning (DL) features extracted from CT images to distinguish benign from malignant ovarian tumors. METHODS: We enrolled 149 patients with pathologically confirmed ovarian tumors. A total of 185 tumors were included and divided into training and testing sets in a 7:3 ratio. All tumors were manually segmented from preoperative contrast-enhanced CT images. CT image features were extracted using radiomics and DL. Five models with different combinations of feature sets were built. Benign and malignant tumors were classified using machine learning (ML) classifiers. The model performance was compared with five radiologists on the testing set. RESULTS:  Among the five models, the best performing model is the ensemble model with a combination of radiomics, DL, and clinical feature sets. The model achieved an accuracy of 82%, specificity of 89% and sensitivity of 68%. Compared with junior radiologists averaged results, the model had a higher accuracy (82% vs 66%) and specificity (89% vs 65%) with comparable sensitivity (68% vs 67%). With the assistance of the model, the junior radiologists achieved a higher average accuracy (81% vs 66%), specificity (80% vs 65%), and sensitivity (82% vs 67%), approaching to the performance of senior radiologists. CONCLUSIONS:  We developed a CT-based AI model that can differentiate benign and malignant ovarian tumors with high accuracy and specificity. This model significantly improved the performance of less-experienced radiologists in ovarian tumor assessment, and may potentially guide gynecologists to provide better therapeutic strategies for these patients.

4.
Front Neurol ; 13: 976695, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36388226

RESUMEN

Objective: To explore the value of color Doppler ultrasonography (CDU) to predict preoperatively and evaluate postoperatively the collateral development of two common revascularizations in patients with moyamoya disease (MMD). Methods: We prospectively enrolled 49 patients with MMD who underwent unilateral superficial temporal artery (STA) -middle cerebral artery (MCA) anastomosis or encephalo-duro-arterio-synangiosis (EDAS). The parameters of the extracranial arteries, including STA, internal carotid artery (ICA), external carotid artery (ECA), and vertebral artery (VA), were performed before and at 3-6 months after surgery. DSA results were used to assess surgical collateral development. Results: To predict good collateral development before STA-MCA anastomosis, the preoperative D > 1.75 mm in the STA had the highest area under the Receiver Operating Characteristic curve (AUC). To predict good collateral development before EDAS, the preoperative EDV > 12.00 cm/s in the STA had the highest AUC. To evaluate the good collateral development after STA-MCA anastomosis, the postoperative EDV > 16.50 cm/s in the STA had the highest AUC. To evaluate the good collateral development after EDAS, an increase of D of 0.15 mm in the STA had the highest AUC. Logistic regression analysis showed that the preoperative RI and EDV in the STA were highly correlated with collateral development. Besides, the preoperative RI was an independent risk factor for collateral development. Conclusion: CDU could predict preoperatively and evaluate postoperatively the collateral development of STA-MCA anastomosis and EDAS surgery postoperatively by detecting ultrasound parameters of the STA.

5.
Tissue Eng Regen Med ; 19(6): 1321-1336, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36074328

RESUMEN

BACKGROUND: In the present study, a novel tissue engineering bone graft including platelet rich plasma gel (PRP gel), human umbilical mesenchymal stem cells (HUMSCs) and nanohydroxyapatite/polyamide 66 (nHA-PA66) was constructed. We explored whether the composite scaffolds could enhance the angiogenesis and bone repair capacity in rat femoral large bone defect (LBD). This study aimed to provide evidence for the clinical application of the composite scaffold in LBD treatment. METHODS: PRP was prepared, the platelets and growth factors were measured. HUMSCs were isolated and identified. the osteogenic capacity of PRP in vitro was measured. Then HUMSCs-PRP-gel/nHA-PA66 composite scaffolds were synthesized and observed. The proliferation and osteogenesis differentiation of HUMSCs on the composite scaffold was measured. The angiogenic capacity of PRP in vitro was measured by capillary-like tube formation assay. Finally, the angiogenesis and bone repair capacity of the composite scaffolds was measured in rat LBD. RESULTS: PRP contained high level of platelets and growth factors after activation, and promoted osteogenic and angiogenic differentiation in vitro. The HUMSCs-PRP-gel/nHA-PA66 composite scaffold was porosity and promoted the proliferation and osteogenesis differentiation of HUMSCs. At 12th weeks, more micro-vessels and new bone were formed around the composite scaffolds compared with other groups, the defect was almost repaired. CONCLUSION: Our study for the first time identified that the combination of PRP gel, HUMSCs and nHA-PA66 scaffold could significantly promote angiogenesis and bone regeneration in rat LBD, which may have implications for its further application in clinical LBD treatment.


Asunto(s)
Células Madre Mesenquimatosas , Plasma Rico en Plaquetas , Humanos , Ratas , Animales , Nylons , Proliferación Celular , Regeneración Ósea , Plasma Rico en Plaquetas/metabolismo , Células Madre Mesenquimatosas/metabolismo
6.
Sci Total Environ ; 835: 155441, 2022 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-35469881

RESUMEN

With the rapid development of the mining industry, the pollution of heavy metal(loid)s in soils near copper (Cu) mining sites is a significant concern worldwide. However, the pollution status and probabilistic health risks of heavy metal(loid)s of soils associated with Cu mines, have rarely been studied on a global scale. In this study, eight heavy metal(loid) concentrations in soil samples taken near 102 Cu mining sites worldwide were obtained through a literature review. Based on this database, the heavy metal(loid) pollution and ecological risk in soils near Cu mines were evaluated. Most of the study sites exceeded the moderately to heavily polluted levels of Cu and Cd; compared to other regions, higher pollution levels were observed at sites in Oman, China, Australia, and the United Kingdom. Soil pollution by Cd, Pb, and Zn at agricultural sites was higher than that in non-agricultural sites. In addition, these heavy metal(loid)s produced a high ecological risk to soils around Cu mining sites in which the contribution of Cd, Cu, and As reached up to 46.5%, 21.7%, and 18.4%, respectively. The mean hazard indices of the eight heavy metal(loid)s were 0.209 and 0.979 for adults and children, respectively. The Monte Carlo simulation further predicted that 1.40% and 29.9% of non-carcinogenic risk values for adults and children, respectively, exceeded the safe level of 1.0. Moreover, 84.5% and 91.0% of the total cancer risk values for adults and children, respectively, exceeded the threshold of 1E-04. Arsenic was the main contributor to non-carcinogenic risk, while Cu had the highest exceedance of carcinogenic risk. Our findings indicate that the control of Cu, Cd, and As should be prioritized because of their high incidence and significant risks in soils near Cu mines. These results provide valuable inputs for policymakers in designing effective strategies for reducing the exposure of heavy metal(loid)s in this area worldwide.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Adulto , Cadmio/análisis , Niño , China , Cobre/análisis , Monitoreo del Ambiente , Contaminación Ambiental/análisis , Humanos , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis
7.
Inorg Chem ; 61(15): 5737-5743, 2022 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-35385262

RESUMEN

Xe/Kr separation is industrially important but remains a daunting issue in chemical separations. Herein, a fluorinated metal-organic framework (MOF), [Ni2(µ2-O)(TFBPDC)(tpt)2]n (named JXNU-13-F), built from 3,3',5,5'-tetrakis(fluoro)biphenyl-4,4'-dicarboxylic (TFBPDC2-) and 2,4,6-tri(4-pyridinyl)-1,3,5-triazine (tpt) ligands is provided. JXNU-13-F displays a three-dimensional (3D) framework constructed from distorted octahedral cages and an impressive Xe capacity of 144 cm3 g-1 at 273 K and 1 bar, ranking among top MOFs. The high Xe uptake and moderate Xe/Kr adsorption selectivity endow JXNU-13-F with efficient Xe/Kr separation demonstrated by experimental column breakthrough tests. The comparative studies of gas adsorption between isostructural JXNU-13-F and JXNU-13 (the nonfluorinated analogue ([Ni2(µ2-O)(BPDC))(tpt)2]n with biphenyl-4,4'-dicarboxylic (BPDC2-)) revealed that the F groups serve as the innocent groups during the Xe and Kr adsorption in JXNU-13-F. Thus, a combination of highly hydrophobic and π-electron-rich pore surfaces made of aromatic rings with strong interactions with the Xe atom possessing large polarizability and appropriate pore sizes that match well Xe having a large atom diameter has resulted in high Xe uptake and effective Xe/Kr separation characteristics of JXNU-13-F.

8.
Environ Geochem Health ; 44(11): 3765-3777, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35037140

RESUMEN

Since toxic element pollution is widespread in soils near gold mines due to increasing mining activities, the adverse effects of potentially toxic elements (PTEs) in the soils on ecological systems and human health cannot be ignored. However, assessments of PTE pollution in soils and their ecological-health risks on a national scale are still limited. Here, the concentrations of eight PTEs in soils near gold mines throughout China were obtained from published articles. Based on these data, the pollution levels and ecological-health risks of the eight PTEs in soils were comprehensively estimated. The results showed that the average contents of As, Cr, Cd, Pb, Hg, Cu, Ni, and Zn were 81.62, 79.82, 1.04, 206.03, 2.05, 40.82, 71.82, and 130.42 mg kg-1, respectively, which exceeded the corresponding background values for soils. Most of the examined soils were heavily polluted by Hg and Cd, and higher pollution levels were found in the Henan and Shaanxi Provinces than in other regions. The average potential ecological risk value of all PTEs was 2534.71, indicating the presence of very high risks. Contribution of Hg to the potential ecological risk was more than 80%. For adults, all hazard index (HI) values of noncarcinogenic risks were below the safe level of 1.00. For children, none of the HI values exceeded the safe level, with the exception of As (HI = 1.81); nevertheless, four PTEs (As, Cr, Cu, and Ni) presented unacceptable carcinogenic risks. This study provides scientific basis for controlling PTE contamination and reducing the health risks in soils near gold mines worldwide.


Asunto(s)
Mercurio , Metales Pesados , Contaminantes del Suelo , Niño , Adulto , Humanos , Suelo , Metales Pesados/toxicidad , Metales Pesados/análisis , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Oro/toxicidad , Oro/análisis , Cadmio/análisis , Plomo/análisis , Monitoreo del Ambiente/métodos , Medición de Riesgo , Mercurio/análisis , China
9.
Sci Total Environ ; 816: 151556, 2022 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-34752878

RESUMEN

Soil pollution by potentially toxic trace elements (PTEs) near uranium (U) mines arouses a growing interest worldwide. However, nearly all studies have focused on a single site or only a few sites, which may not fully represent the soil pollution status at the global scale. In this study, data of U, Cd, Cr, Pb, Cu, Zn, As, Mn, and Ni contents in U mine-associated soils were collected and screened from published articles (2006-2021). Assessments of pollution levels, distributions, ecological, and human health risks of the nine PTEs were analysed. The results revealed that the average contents of the U, Cd, Cr, Pb, Cu, Zn, As, Mn, and Ni were 39.88-, 55.33-, 0.88-, 3.81-, 3.12-, 3.07-, 9.26-, 1.83-, and 1.17-fold greater than those in the upper continental crust, respectively. The pollution assessment showed that most of the studied soils were heavily polluted by U and Cd. Among them, the U mine-associated soils in France, Portugal, and Bulgaria exhibited significantly higher pollution levels of U and Cd when compared to other regions. The average potential ecological risk value for all PTEs was 3358.83, which indicated the presence of remarkably high risks. Among the PTEs, Cd and U contributed more to the potential ecological risk than the other elements. The health risk assessment showed that oral ingestion was the main exposure route for soil PTEs; and the hazard index (HI) values for children were higher than those for adult males and females. For adult males and females, all hazard index values for the noncarcinogenic risks were below the safe level of 1.00. For children, none of the HI values exceeded the safe level, with the exception of U (HI = 3.56) and As (HI = 1.83), but Cu presented unacceptable carcinogenic risks. This study provides a comprehensive analysis that demonstrates the urgent necessity for treating PTE pollution in U mine-associated soils worldwide.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Oligoelementos , Uranio , Adulto , Niño , China , Monitoreo del Ambiente , Humanos , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis
10.
Pharmacol Res ; 159: 105010, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32544428

RESUMEN

AMD3100 (plerixafor), a CXCR4 antagonist, has opened a variety of avenues for potential therapeutic approaches in different refractory diseases. The CXCL12/CXCR4 axis and its signaling pathways are involved in diverse disorders including HIV-1 infection, tumor development, non-Hodgkin lymphoma, multiple myeloma, WHIM Syndrome, and so on. The mechanisms of action of AMD3100 may relate to mobilizing hematopoietic stem cells, blocking infection of X4 HIV-1, increasing circulating neutrophils, lymphocytes and monocytes, reducing myeloid-derived suppressor cells, and enhancing cytotoxic T-cell infiltration in tumors. Here, we first revisit the pharmacological discovery of AMD3100. We then review monotherapy of AMD3100 and combination use of AMD3100 with other agents in various diseases. Among those, we highlight the perspective of AMD3100 as an immunomodulator to regulate immune responses particularly in the tumor microenvironment and synergize with other therapeutics. All the pre-clinical studies support the clinical testing of the monotherapy and combination therapies with AMD3100 and further development for use in humans.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Antineoplásicos/uso terapéutico , Bencilaminas/uso terapéutico , Ciclamas/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Receptores CXCR4/antagonistas & inhibidores , Animales , Fármacos Anti-VIH/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Bencilaminas/efectos adversos , Ciclamas/efectos adversos , Contaminación de Medicamentos , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , Humanos , Neoplasias/inmunología , Neoplasias/metabolismo , Enfermedades de Inmunodeficiencia Primaria/tratamiento farmacológico , Enfermedades de Inmunodeficiencia Primaria/inmunología , Enfermedades de Inmunodeficiencia Primaria/metabolismo , Receptores CXCR4/metabolismo , Transducción de Señal , Microambiente Tumoral , Verrugas/tratamiento farmacológico , Verrugas/inmunología , Verrugas/metabolismo
11.
Pharmacol Res ; 157: 104843, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32360582

RESUMEN

Both antitumor and protumor property of mesenchymal stem cells (MSCs) have been demonstrated. We hypothesize that this contradiction is due to the heterogeneity of MSC subsets and that extracellular vesicles (EVs) from distinct MSC subsets can transfer the corresponding antitumor activities. Here we evaluated the antitumor activities of two subsets of adipose-derived mesenchymal stem cells (ADSCs) and ADSC-derived EVs (ADSC-EVs) in immunocompetent syngeneic mouse models of breast cancer. We identified CD90high and CD90low ADSC subsets and demonstrated that CD90high ADSCs could be converted into CD90low ADSCs by stimulation with LPS. CD90low ADSCs and its derived EVs significantly inhibited tumor growth in tumor-bearing mice. Benefit of tumor control were associated with decreased tumor cell proliferation and migration, and enhanced tumor cell apoptosis mediated by ADSC-EVs. Antioncogenic miRNA-16-5p loaded CD90low ADSC-EVs further significantly enhanced antitumor activities. Taken together, this study represents the first attempt to apply our newly identified antitumor ADSCs and its derived EVs in preclinical treatment of breast cancer. This study also provides the evidence that EVs can serve as a novel and effective therapeutics or drug delivery vesicle. This new therapeutic approach could be potentially applicable to breast cancer and many other types of cancer.


Asunto(s)
Neoplasias de la Mama/terapia , Vesículas Extracelulares/trasplante , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Tejido Adiposo/citología , Animales , Apoptosis , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Vesículas Extracelulares/inmunología , Vesículas Extracelulares/metabolismo , Femenino , Células Madre Mesenquimatosas/inmunología , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , Invasividad Neoplásica , Fenotipo , Antígenos Thy-1/metabolismo , Carga Tumoral
12.
Nanotechnology ; 31(1): 015501, 2020 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-31530749

RESUMEN

Here we develop a magnetoelastic (ME) nano-biosensor based on the competitive strategy for the detection of a carcinoembryonic antigen (CEA). Specifically, the gold-coated ME material provided a platform and the thiolated single-stranded DNA (HS-DNA) containing a half-complementary sequence towards the CEA aptamer was modified on the surface via Au-S bonding. DNA-templated silver nanoclusters (DNA-AgNCs) containing another half-complementary sequence towards the aptamer were used to amplify the signals by about 2.1 times, compared to those obtained using just the aptamer. CEA aptamers as a bio-recognition element were employed to link HS-DNA and DNA-AgNCs through DNA hybridization. The CEA aptamer preferentially combined with CEA rather than hybridized with DNA. Due to the magnetostrictive nature of the ME materials, the resonant frequency of the nano-biosensor would increase along with the release of DNA-AgNCs and CEA aptamers. The modification process was demonstrated by UV-vis spectra, x-ray photoelectron spectroscopy (XPS), Raman spectroscopy, transmission electron microscope (TEM) and an atomic force microscope (AFM). The nano-biosensor has a linear response to the logarithmic CEA concentrations ranging from 2 pg ml-1 to 6.25 ng ml-1, with a limit of detection (LOD) of 1 pg ml-1 and a sensitivity of 105.05 Hz/ng · ml-1. This study provides a low-cost, highly sensitive and wireless method for selective detection of CEA.


Asunto(s)
Aptámeros de Nucleótidos/química , Antígeno Carcinoembrionario/análisis , ADN de Cadena Simple/química , Técnicas Biosensibles/métodos , Humanos , Límite de Detección , Nanopartículas del Metal , Microscopía de Fuerza Atómica , Microscopía Electrónica de Transmisión , Plata/química , Espectrometría Raman
13.
Fitoterapia ; 137: 104191, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31163200

RESUMEN

8,2'-Diprenylquercetin 3-methyl ether, a natural product with prominent anti-breast cancer activity, is the main active constituent of Sinopodophylli Fructus. A high-performance liquid chromatography with a diode array detector coupled with electrospray ionization ion trap time-of-flight multistage mass spectrometry (HPLC-DAD-ESI-IT-TOF-MSn) method was established and applied to profile and identify the metabolites of 8,2'-diprenylquercetin 3-methyl ether as well as study their distribution in rat organs for the first time. A total of 100 new metabolites were tentatively identified in rats. The metabolic reactions of 8,2'-diprenylquercetin 3-methyl ether in rats in vivo were hydroxylation, methylation, glucuronidation, dehydrogenation, sulfation, polymerization and cysteine conjugation as well as the specific reactions of leucine/isoleucine, proline, and vitamin C conjugation. The detected metabolites included 77 in faeces, 50 in urine, 11 in plasma, 50 in the small intestine, 32 in the stomach, 23 in the liver, 9 in the lungs, 9 in the spleen, 8 in the heart, and 6 in the kidneys. The results indicated that the small intestine, stomach, and liver were the major organs for the distribution of 8,2'-diprenylquercetin 3-methyl ether metabolites. Furthermore, 27 metabolites showed various bioactivities predicted by the analysis of "PharmMapper", among which 9 metabolites showed anti-cancer activity. These results are very useful for understanding the metabolism and pharmacological actions as well as the effective forms and toxic actions of 8,2'-diprenylquercetin 3-methyl ether in vivo; moreover, they will lay the foundation for further studies on the metabolism of prenylflavonoid compounds.


Asunto(s)
Quercetina/análogos & derivados , Animales , Berberidaceae/química , Cromatografía Líquida de Alta Presión , Frutas/química , Masculino , Estructura Molecular , Quercetina/metabolismo , Ratas , Ratas Sprague-Dawley , Espectrometría de Masa por Ionización de Electrospray , Distribución Tisular
14.
J Autoimmun ; 102: 96-113, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31130368

RESUMEN

The subset of regulatory T (Treg) cells, with its specific transcription Foxp3, is a unique cell type for the maintenance of immune homeostasis by controlling effector T (Teff) cell responses. Although it is common that a defect in Treg cells with Treg/Teff disorder causes autoimmune diseases; however, the precise mechanisms are not thoroughly revealed. Here, we report that miR-34a could attenuate human and murine Foxp3 gene expression via targeting their 3' untranslated regions (3' UTR). The human miR-34a, increased in peripheral blood mononuclear cells (PBMCs) and CD4+ T cells from rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) patients, displayed a positive correlation with some serum markers of inflammation including rheumatoid factor (RF), anti-streptolysin antibody (ASO), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as Th17 signature gene RORγt, but inversely correlated with the mRNA expression levels of FOXP3. In addition, murine miR-34a levels were downregulated in TGF-ß-induced Treg cells but upregulated in Th17 cells induced in vitro compared to activated CD4+ T cells. It has also been demonstrated that elevated miR-34a disrupting Treg/Th17 balance in vivo contributed to the progress of pathogenesis of collagen induced arthritis (CIA) mice. Furthermore, IL-6 and TNF-α were responsible for the upregulation of miR-34a and downregulation of Foxp3, which was reverted by the addition of NF-κB/p65 inhibitor BAY11-7082, thus indicating that NF-κB/p65 inhibited Foxp3 expression in an miR-34a-dependent manner. Finally, IL-6 or TNF-α-activated p65 could bind to the miR-34a promotor and enhance its activity, resulting in upregulation of its transcription. Taken together, we show that NF-κB activated by inflammatory cytokines, such as IL-6 and TNF-α, ameliorates Foxp3 levels via regulating miR-34a expression, which provides a new mechanistic and therapeutic insight into the ongoing of autoimmune diseases.


Asunto(s)
Artritis Reumatoide/inmunología , Factores de Transcripción Forkhead/metabolismo , Interleucina-6/inmunología , Lupus Eritematoso Sistémico/inmunología , MicroARNs/genética , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/inmunología , Regiones no Traducidas 3'/genética , Adulto , Anciano , Animales , Antiestreptolisina/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Línea Celular , Femenino , Células HEK293 , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/sangre , Regiones Promotoras Genéticas , Factor Reumatoide/sangre , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Células Th17/citología , Células Th17/inmunología , Factor de Transcripción ReIA/antagonistas & inhibidores
15.
Oncol Rep ; 39(3): 1197-1206, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29328463

RESUMEN

Increasing evidence has experimentally proved the competitive endogenous RNA (ceRNA) hypothesis that long non-coding RNA (lncRNA) can affect the expression of RNA targets by competitively combining microRNA (miRNA) via miRNA response elements. However, an extensive ceRNA network of thyroid carcinoma in a large cohort has not been evaluated. We analyzed the RNAseq and miRNAseq data of 348 cases of primary papillary thyroid cancer (PTC) patients with clinical information downloaded from The Cancer Genome Atlas (TCGA) project to search for potential biomarkers or therapeutic targets. A computational approach was applied to build an lncRNA-miRNA-mRNA regulatory network of PTC. In total, 780 lncRNAs were detected as collectively dysregulated lncRNAs in all 3 PTC variants compared with normal tissues (fold change >2 and false discovery rate <0.05). The interactions among 45 lncRNAs, 13 miRNAs and 86 mRNAs constituted a ceRNA network of PTC. Nine out of the 45 aberrantly expressed lncRNAs were related to the clinical features of PTC patients. However, the expression levels of 3 lncRNAs (LINC00284, RBMS3-AS1 and ZFX-AS1) were identified to be tightly correlated with the patients overall survival (log-rank, P<0.05). The present study identified a list of specific lncRNAs associated with PTC progression and prognosis. This complex ceRNA interaction network in PTC may provide guidance for better understanding the molecular mechanisms underlying PTC.


Asunto(s)
Adenocarcinoma Folicular/genética , Biomarcadores de Tumor/genética , Carcinoma Papilar/genética , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , ARN Largo no Codificante/genética , Neoplasias de la Tiroides/genética , Adenocarcinoma Folicular/patología , Carcinoma Papilar/patología , Estudios de Casos y Controles , Estudios de Cohortes , Bases de Datos Genéticas , Femenino , Estudios de Seguimiento , Humanos , Masculino , MicroARNs , Persona de Mediana Edad , Pronóstico , ARN Mensajero , Tasa de Supervivencia , Neoplasias de la Tiroides/patología
16.
Int J Surg ; 25: 128-33, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26703380

RESUMEN

Liver transplantation is associated with a significantly increased risk of de novo malignancies, but for renal cancer this risk is less clear. We therefore performed a meta-analysis of published studies to determine whether renal cancer risk in liver transplant recipients (LTRs) was increased. To obtain a more precise conclusion, a systematic search was performed in PubMed and Web of Science databases until June 10, 2015. Standardized incidence ratio (SIR) corresponding 95% confidence interval (CI) were used to estimate risk of renal cancer in LTRs. Heterogeneity test, sensitivity analysis, and publishing bias were also performed. We identified 8 eligible studies and performed a meta-analysis on data of 49,654 LTRs with a total follow-up of 121,514.6 patient-years. The SIR for renal cancer was identified a 3.275-fold higher SIR (95% CI: 1.857-5.777; P < 0.001) in LTRs compared with the general population. This systematic review and meta-analysis demonstrated that the LTRs was associated with a significant increase in the incidence of renal cancer. Such association suggests that yearly routine post-transplant surveillance is need for renal cancer in LTRs.


Asunto(s)
Neoplasias Renales/etiología , Trasplante de Hígado/efectos adversos , Adulto , Femenino , Humanos , Incidencia , Neoplasias Renales/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(5): 1277-82, 2011 Oct.
Artículo en Chino | MEDLINE | ID: mdl-22040988

RESUMEN

The purpose of this study was to assess the efficacy and toxicity of HAI regimen [(homoharringtonine 2.5 mg/(m(2)×d), days 1 - 7; cytarabine 150 mg/(m(2)×d), days 1 - 7; idarubicin 9 mg/(m(2)×d), days 1 - 7)] for induction treatment of newly diagnosed acute myeloid leukemia (AML) (except acute promyelocytic leukemia). 31 patients with newly diagnosed AML, aged 39 (14 - 58) years, were enrolled in this clinical study. The complete remission (CR) rate, especially after one course, the overall survival (OS) rate and relapse free survival (RFS) rate were estimated. The outcomes were compared between different prognostic groups according to World Health Organization (WHO) classification, genetics and initial WBC count. Safety was evaluated using standard WHO criteria. The results showed that 26 patients (84%) achieved CR after 1 course of induction. The CR rate for the patients with favorable, intermediate and unfavorable cytogenetics was 90%, 88% and 60% respectively. All 7 patients with a high initial WBC count (≥ 100×10(9)/L) obtained CR, while 19 out of 24 without a high initial WBC count obtained CR. With a median follow-up of 15(range 2-56) months, the estimated 3-year OS rate for all patients and the patients with CR was 44% and 52% respectively. The 3-year RFS rate was 51%. The patients receiving induction chemotherapy died of the chemotherapy. Profound myelosuppression was seen in all patients after the HAI induction with the median duration of neutropenia (ANC < 0.2×10(9)/L) of 16 (6 - 24) days. As the most common toxicity, severe infections (grade III-IV) involved in all the patients and the duration of febris was 6 (1 - 36) days. The incidence of septemia and invasive fungus infection were 19.4% and 45.2% respectively. The incidence of non-infection fever, increased glutamic-pyruvic transaminase (GPT), diarrhea, increased bilirubin and oral cavity mucositis were 6.5%, 6.5%, 3.2%, 3.2%, 3.2% respectively, as the more frequent severe non-hematological toxicities. It is concluded that HAI regimen is a high efficient induction schedule for the newly diagnosed AML, and archive the higher CR rate after one course than DNR/Ara-C standard induction regimen. Side effects are acceptable, except severe infection.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Inducción , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Femenino , Harringtoninas/administración & dosificación , Harringtoninas/uso terapéutico , Homoharringtonina , Humanos , Idarrubicina/administración & dosificación , Idarrubicina/uso terapéutico , Masculino , Persona de Mediana Edad , Adulto Joven
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