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1.
Biochem Pharmacol ; 174: 113830, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32001235

RESUMO

High glucose-induced endothelial dysfunction is a critical initiating factor in the development of diabetic vascular complications. Omentin-1 has been regarded as a novel biomarker of endothelial function in subjects with type-2 diabetes (T2D); however, it is unclear whether omentin-1 has any direct effect in ameliorating high glucose-induced endothelial dysfunction. In the present study, we analyzed the effect of omentin-1 on high glucose-induced endothelial dysfunction in isolated mouse aortas and mouse aortic endothelial cells (MAECs). Vascular reactivity in aortas was measured using wire myography. The expression levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor δ (PPARδ), Akt, endothelial nitric-oxide synthase (eNOS), and endoplasmic reticulum (ER)-stress markers in MAECs were determined by Western blotting. The production of reactive oxygen species (ROS) and nitric oxide (NO) was assessed by diluted fluoroprobe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM DA), respectively. We found that ex vivo treatment with omentin-1 reversed impaired endothelial-dependent relaxations (EDR) in mouse aortas after high-glucose insult. Elevated ER-stress markers, oxidative stress, and reduction of NO production induced by high glucose in MAECs were reversed by omentin-1 treatment. Omentin-1 also effectively reversed tunicamycin-induced ER stress responses in MAECs, as well as ameliorated impairment of endothelial-dependent relaxation in mouse aortas. Moreover, omentin-1 increased AMPK phosphorylation with a subsequent increase in PPARδ expression, while also restoring the decreased phosphorylation of Akt and eNOS. The effects of omentin-1 were abolished by cotreatment of compound C (AMPK inhibitor) and GSK0660 (PPARδ antagonist). These data indicate that omentin-1 protects against high glucose-induced vascular-endothelial dysfunction through inhibiting ER stress and oxidative stress and increasing NO production via activation of AMPK/PPARδ pathway.

2.
Waste Manag ; 102: 561-568, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31770690

RESUMO

Catalytic fast co-pyrolysis of waste greenhouse plastic films and rice husk over a hierarchical HZSM-5/MCM-41 catalyst was performed in an analytical Py-GC/MS. We evaluated the effect of pyrolysis temperature and the ratio of rice husk to waste greenhouse plastic films on the total peak area of condensable organic products and CO2. In order to evaluate synergy possibilities among the two feedstocks, we performed non-catalytic pyrolysis and catalytic fast pyrolysis of rice husk and waste greenhouse plastic films separately. In addition, we report results for the catalytic fast co-pyrolysis of the mixture rice husk and waste greenhouse plastic films. The maximum relative content of hydrocarbons from catalytic fast co-pyrolysis of rice husk and waste greenhouse plastic films is obtained at 600 °C. When the mass ratio of rice husk to waste greenhouse plastic films is 1:1.5, the relative content of hydrocarbons reaches a maximum (71.1%). The hierarchical micro-mesoporous composite molecular sieve used in this work has outstanding catalytic activity and increases the relative content of hydrocarbons.


Assuntos
Oryza , Biocombustíveis , Catálise , Cromatografia Gasosa-Espectrometria de Massas , Temperatura Alta , Plásticos , Pirólise
3.
Sci Total Environ ; 703: 134605, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31731164

RESUMO

We performed microwave-assisted catalytic fast pyrolysis (MACFP) of rice husk (RH) over an alkali-treated HZSM-5 zeolite, for production of hydrocarbons. The treatment consisted in the modification of the HZSM-5 by the organic base tetrapropylammonium hydroxide (TPAOH) solution at several concentrations. We characterized the resulting catalysts by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption-desorption, and temperature-programmed sorption of ammonia (NH3-TPD). The results suggest that the TPAOH treatment generated mesoporous structures in the HZSM-5, while preserving its microporous structure and crystallinity. We obtained the highest yield (45.9%) of hydrocarbons from MACFP of rice husk (RH) at 550 °C. As the TPAOH concentration increases, the relative content of BTEX hydrocarbons (benzene, toluene, ethylbenzene, and xylene) reaches a maximum value of 22.9% at 2.0 mol/L. A comparison of results obtained over the organic base TPAOH (HZSM-5 modified by 2.0 mol/L TPAOH solution) with those obtained over an inorganic base (HZSM-5 modified by 2.0 mol/L NaOH solution) shows a 4.3% increase in the relative content of monocyclic aromatic hydrocarbons for the TPAOH. In addition, the TPAOH-treated catalyst shows excellent selectivity of BTEX (58.5%), which is higher than the selectivity obtained with the parent HZSM-5 (51.2%) and NaOH-treated HZSM-5 (53.9%). The TPAOH-modified HZSM-5 catalyst effectively reduced coke formation by 4.6% compared to MACFP over the parent HZSM-5, most likely because TPAOH decreases the concentration of strong acidic sites on the outer surface of the catalyst, creating a mesoporous structure while retaining the weak acidic sites on the HZSM-5 inner surface. The new catalyst generated in this work contains a moderate amount of mesopores structures, which allows for effective upgrading of pyrolysis vapors while simultaneously reducing coke formation, thereby addressing a significant problem in the development of the catalytic fast pyrolysis process.

4.
R Soc Open Sci ; 6(11): 191307, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31827862

RESUMO

In order to improve the quality of catalysis products of algae, composite molecular sieve catalyst was prepared by digestion and crystallization of HZSM-5 to reduce the oxygen content of the catalytic products. According to the analysis of the pyrolysis products, the best preparation conditions were chosen of tetra propylammonium hydroxide (TPAOH) solution 2.0 mol l-1, cetyltrimethylammonium bromide (CTAB) solution 10 wt%, crystallization temperature 110°C, digestion-crystallization time: 24-24 h. The results indicate that the main function of catalysts is to promote the conversion of alcohols into hydrocarbons by reducing energy barriers. Catalysed by the composite molecular sieve, the content of alcohols in the pyrolysis products decreased from more than 30% to less than 10%, the content of hydrocarbons increased from 20% to nearly 60%, while all the adverse components remained at a low level, which indicates that the catalytic pyrolysis products are of high quality. The great deoxidation effect of composite molecular sieves is not only due to the expansion of the range of organic matter during re-pyrolysis, but also the increasing of the residence time of pyrolysis products inside the structure for the external mesoporous structure.

5.
Stem Cell Res Ther ; 10(1): 325, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730485

RESUMO

INTRODUCTION: Multiple sclerosis (MS) is one of the most common autoimmune diseases of the central nervous system (CNS). CNS has its own unique structural and functional features, while the lack of precision regulatory element with high specificity as therapeutic targets makes the development of disease treatment in the bottleneck. Recently, the immunomodulation and neuroprotection capabilities of bone marrow stromal stem cells (BMSCs) were shown in experimental autoimmune encephalomyelitis (EAE). However, the administration route and the safety evaluation limit the application of BMSC. In this study, we investigated the therapeutic effect of BMSC supernatant by nasal administration. METHODS: In the basis of the establishment of the EAE model, the BMSC supernatant were treated by nasal administration. The clinical score and weight were used to determine the therapeutic effect. The demyelination of the spinal cord was detected by LFB staining. ELISA was used to detect the expression of inflammatory factors in serum of peripheral blood. Flow cytometry was performed to detect pro-inflammatory cells in the spleen and draining lymph nodes. RESULTS: BMSC supernatant by nasal administration can alleviate B cell-mediated clinical symptoms of EAE, decrease the degree of demyelination, and reduce the inflammatory cells infiltrated into the central nervous system; lessen the antibody titer in peripheral bloods; and significantly lower the expression of inflammatory factors. As a new, non-invasive treatment, there are no differences in the therapeutic effects between BMSC supernatant treated by nasal route and the conventional applications, i.e. intraperitoneal or intravenous injection. CONCLUSIONS: BMSC supernatant administered via the nasal cavity provide new sights and new ways for the EAE therapy.

6.
J Mol Cell Cardiol ; 135: 134-148, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398346

RESUMO

Cellular autoimmune responses, especially those mediated by T-cells, play vital roles in the immunopathogenesis of dilated cardiomyopathy (DCM). Metabolic reprogramming directly controls T-cell function, imprinting distinct functional fates. However, its contribution to T-cell dysfunction and the immunopathogenesis of DCM is unknown. Here, we found that in DCM patients, CD4+ T-cells exhibited immune dysfunction and glycolytic metabolic reprogramming based on extracellular acidification and oxygen consumption rates. Similar results were observed in splenic and cardiac CD4+ T-cells from autoimmune-induced DCM mice. In vitro, the glycolysis inhibitor 2-deoxy-d-glucose (2-DG) reversed T-cell dysfunction; thus, heightened metabolic activity directly controls CD4+ T-cell immunological status. Adoptive transfer of CD4+ T-cells from DCM mice to normal recipients induced cardiac remodeling and cardiac T-cell dysfunction. Strikingly, these effects were abolished by preconditioning cells with 2-DG, indicating that CD4+ T-cell dysfunction partially induced by metabolic reprogramming contributes to cardiac remodeling. Moreover, the microRNA let-7i modulated the metabolism and function of T-cells from DCM mice by directly targeting Myc. Collectively, our results show that metabolic reprogramming occurs in T-cells of autoimmune-induced DCM mice and patients. Further, our findings highlight that glycolytic metabolism is a critical contributor to T-cell dysfunction and DCM immunopathogenesis. Our data position the modulation of the metabolism as a central integrator for T-cell function, representing a promising strategy against autoimmune-mediated DCM progression.

7.
Eur J Immunol ; 49(12): 2184-2194, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31411745

RESUMO

MicroRNA 182 is important for the clonal expansion of CD4+ T cells (Th) following IL-2 stimulation and is a potential therapeutic target for autoimmune diseases. In the present study, we investigated the role of microRNA 182 in the differentiation of pro-inflammatory CD4+ T helper cell by overexpressing or silencing microRNA 182 expression both in in vivo and in vitro settings. We report that in the studied Chinese cohort, microRNA 182 is upregulated in patients with relapse and remitting multiple sclerosis (RRMS) and this upregulation is associated with increased IFN-γ producing CD4+ Th1 cells in the circulation. In the murine experimental autoimmune encephalomyelitis (EAE) model, global microRNA 182 overexpression exacerbates clinical symptoms and results in augmented CD4+ IFN-γ+ Th1 and CD4+ IL-17+ Th17 differentiation in vivo. Addition of microRNA 182 mimics in vitro represses both the protein expression and transcriptional activity of hypoxia induced factor 1α (HIF-1α) but increases the level of IFN-γ transcripts in sorted murine CD4+ T cells. Together, our results provide evidence that microRNA 182 may be one of the transitional hubs contribution to regulate Th cells expansion in response to self-antigens and differentiation of antigen specific Th cells during the progression of autoimmune inflammations.

8.
J Hypertens ; 37(12): 2371-2379, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31356404

RESUMO

OBJECTIVE: Few epidemiological studies concentrated on dietary carotenoids and hypertension since new hypertension guideline released in 2017. Thus, this study was aimed to evaluate their association. METHODS: Data from National Health and Nutrition Examination Survey (NHANES) 2007-2014 were used in this cross-sectional study. Dietary carotenoids data were obtained from 24-h dietary recall interviews. Hypertension was defined as SBP at least 130 mmHg or DBP at least 80 mmHg, taking antihypertensive medicine or self-report. Logistic regression models and restricted cubic spline models were applied to explore the associations between α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein with zeaxanthin, and total carotenoids from diet and supplements and hypertension. Total carotenoids showed significant reductive risk of hypertension at 100 µg/kg per day and over. RESULTS: A total of 17 398 adults aged 20 years and over were identified. High dose of ß-carotene, lycopene, lutein with zeaxanthin, and total carotenoids were significantly associated with decreased risk of hypertension in crude results. After multivariate-adjustment in model 2, the odds ratios (OR) with 95% confidence intervals (CI) of ß-cryptoxanthin, lycopene, lutein with zeaxanthin and total carotenoids for hypertension were 0.79 (0.67-0.93), 0.85 (0.73-0.98), 0.69 (0.58-0.83), 0.73 (0.62-0.86) for the highest versus lowest quartile intakes, respectively. Dose-response analyses showed that all of the carotenoids were inversely associated with hypertension in a linear manner. Total carotenoids showed significant effect of lower risk of hypertension at 100 µg/kg per day. CONCLUSION: Intakes of α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein with zeaxanthin, and total carotenoids were inversely associated with hypertension in US adults. The intake of total carotenoids was suggested at least 100 µg/kg per day for general adult population.

9.
J Trace Elem Med Biol ; 53: 41-48, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30910205

RESUMO

OBJECTIVE: The association of serum zinc (Zn), copper (Cu) with the risk of hypertension (HT) remains controversial. Therefore, we conducted a meta-analysis to explore the relationships. METHODS: We searched relevant literatures on PubMed and Web of Science up to September 2018. Pooled standard mean difference (SMD) with corresponding 95% confidence interval (CI) was calculated by random effects model.I2 was used to evaluate heterogeneity among studies. RESULTS: 25 articles of serum Zn and 22 articles of serum Cu were included in meta-analysis. HT patients had lower serum Zn [SMD (95%CI): -0.612(-0.951, -0.274), z = 3.54, Pfor z <0.001; I2 = 97.0%, PforI2 <0.001], whereas no significant difference of serum Cu was shown between HT patients and controls [SMD (95%CI): 0.153(-0.101, 0.407)]. Also, male HT patients had lower serum Zn [SMD (95%CI): -1.443(-2.868, -0.017), z = 1.98, Pfor z = 0.047; I2 = 98.8%, PforI2 <0.001]. In subgroup analysis, a lower serum Zn was observed in HT patients in studies conducted in Europe [-1.066(-1.759, -0.374)], in case-control studies [-0.718(-1.294, -0.142)], in matched case-control studies [-0.939(-1.646, -0.233)] and studies involving treated patients [-1.416(-2.195, -0.638)]. Meanwhile, a higher serum Cu was found in HT patients in studies conducted in Africa [1.96(1.402, 2.518)], and in matched case-control studies [0.655(0.204, 1.107)]. CONCLUSION: The present meta-analysis indicates that serum Zn level in HT patients was significantly lower than that in controls, while no significantly different serum Cu level was found between HT patients and controls. Future studies are needed to confirm these results in future research.


Assuntos
Cobre/sangue , Hipertensão/sangue , Zinco/sangue , Estudos de Casos e Controles , Humanos
10.
Acta Biomater ; 78: 111-122, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30099199

RESUMO

Recreating tissue-specific microenvironments of the extracellular matrix (ECM) in vitro is of broad interest for the fields of tissue engineering and organ-on-a-chip. Here, we present biofunctional ECM protein fibres and suspended membranes, with tuneable biochemical, mechanical and topographical properties. This soft and entirely biologic membrane scaffold, formed by micro-nano-fibres using low voltage electrospinning, displays three unique characteristics for potential cell culture applications: high-content of key ECM proteins, single-layered mesh membrane, and flexibility for in situ integration into a range of device setups. Extracellular matrix (ECM) powder derived from urinary bladder, was used to fabricate the ECM-laden fibres and membranes. The highest ECM concentration in the dry protein fibre was 50 wt%, with the rest consisting of gelatin. Key ECM proteins, including collagen IV, laminin, and fibronectin, were shown to be preserved post the biofabrication process. The single fibre tensile Young's modulus can be tuned for over two orders of magnitude between ∼600 kPa and 50 MPa depending on the ECM content. Combining the fibre mesh printing with 3D printed or microfabricated structures, culture devices were constructed for endothelial layer formation, and a trans-membrane co-culture formed by glomerular cell types of podocytes and glomerular endothelial cells, demonstrating feasibility of the membrane culture. Our cell culture observation points to the importance of membrane mechanical property and re-modelling ability as a factor for soft membrane-based cell cultures. The ECM-laden fibres and membranes presented here would see potential applications in in vitro assays, and tailoring structure and biological functions of tissue engineering scaffolds. STATEMENT OF SIGNIFICANCE: Recreating tissue-specific microenvironments of the extracellular matrix (ECM) is of broad interest for the fields of tissue engineering and organ-on-a-chip. Both the biochemical and biophysical signatures of the engineered ECM interplay to affect cell response. Currently, there are limited biomaterials processing methods which allow to design ECM membrane properties flexibly and rapidly. Solvents and additives used in many existing processes also induced unwanted ECM protein degradation and toxic residues. This paper presents a solution fibre spinning technique, where careful selection of the solution combination led to well-preserved ECM proteins with tuneable composition. This technique also provides a highly versatile approach to fabricate ECM fibres and membranes, leading to designable fibre Young's modulus for over two orders of magnitude.


Assuntos
Matriz Extracelular/metabolismo , Nanofibras/química , Animais , Células Cultivadas , Módulo de Elasticidade , Elementos , Humanos , Membranas , Podócitos/citologia , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico , Suínos , Resistência à Tração , Engenharia Tecidual
11.
Genomics ; 110(6): 337-346, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29366861

RESUMO

Long non-coding RNAs have the potential to regulate immune responses. Their impact on multiple sclerosis has remained elusive. For illustrating their roles in experimental autoimmune encephalomyelitis (EAE) pathogenesis, we investigated the differential expression of lncRNAs and mRNAs in CD4+Th cells obtained from myelin oligodendrocytic glycoprotein35-55(MOG35-55)-induced EAE and complete Freund's adjuvant (CFA) controls. We observed differential expression of 1112 lncRNAs and 519 mRNAs in CD4+Th cells. The functional network showed lncRNAs had the capacity to modulate EAE pathogenesis via regulating many known EAE regulators such as Ptpn6. Predicting the function of lncRNAs demonstrated that dysregulated lncRNAs were closely associated with the development of EAE. These dysregulated lncRNAs may have function in EAE and they could be novel biomarkers and therapeutic targets of EAE. However, the precise mechanisms and biological functions of these specific lncRNAs in EAE pathogenesis require further study.


Assuntos
Encefalomielite Autoimune Experimental/metabolismo , Regulação da Expressão Gênica , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Linfócitos T Auxiliares-Indutores/metabolismo , Animais , Encefalomielite Autoimune Experimental/genética , Feminino , Perfilação da Expressão Gênica , Camundongos , Glicoproteína Mielina-Oligodendrócito/farmacologia , Glicoproteína Mielina-Oligodendrócito/toxicidade , Proteína Tirosina Fosfatase não Receptora Tipo 6/genética , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos
12.
Food Funct ; 8(8): 2663-2671, 2017 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-28675204

RESUMO

The effect of soybean protein on blood pressure (BP) in postmenopausal women is controversial, so we aimed to conduct a systematic review and a meta-analysis of published randomized controlled trials (RCTs) to investigate whether supplementation with soy protein improves their blood pressure. PubMed and Embase were searched up to February 2016. Weighted mean differences were calculated for net changes in BP by using fixed-effect or random-effect models. Subgroup and meta-regression analyses were performed to clarify heterogeneity among the trials. A total of twelve trials (1551 postmenopausal women participants) were included in the present meta-analysis. The overall pooled estimates of the effect of soy protein indicated a significant effect on systolic blood pressure (SBP) (mean difference: -3.03 mmHg; 95% CI: -5.03, -1.02; P = 0.003) and diastolic blood pressure (DBP) (mean difference: -0.71 mmHg; 95% CI: -1.26, -0.16; P = 0.012). Subgroup analyses further demonstrated that soy protein intake ≥25 g d-1 significantly reduced BP, and the mean difference in SBP and DBP was -4.62 mmHg (95% CI: -8.42, -0.81; P = 0.04) and -1.63 mmHg (95% CI: -2.85, -0.41; P = 0.009), respectively. Soy isoflavone intake ≥100 mg d-1 had a better reduction effect both in SBP (-5.47 mmHg; 95% CI: -8.42, -2.51; P = 0.00) and DBP (-2.03 mmHg; 95% CI: -3.35, -0.72; P = 0.002). However, soy protein intake <25 g d-1 or soy isoflavone intake <100 mg d-1 had no such effects (P > 0.05). This meta-analysis suggests that ingestion of ≥25 g soy protein per day has BP-lowering effects, and the improvements in BP may be due to the isoflavones component of soy protein. More high-quality RCTs need to be carried out to confirm the present findings.


Assuntos
Pressão Sanguínea , Pós-Menopausa/fisiologia , Proteínas de Soja/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas de Soja/química
13.
J Leukoc Biol ; 101(2): 507-517, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27443879

RESUMO

The classically activated (M1) macrophage has been shown to play an indispensable role in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). However, most studies focus on the effect of macrophage on CNS demyelination of EAE; whether the M1 macrophage participates in early EAE and the molecular mechanism underlying remains unclear. Here, we showed that the immunity-related GTPase family member 1 (Irgm1), also known as LRG-47, was expressed in M1 macrophages of draining lymph nodes (dLNs) from C57BL/6 mice with early EAE, and the IRGM1 heterozygote substantially reduced M1 macrophage accumulation in dLNs and spleen of the primary EAE stage. In vitro silence of IRGM1 in M1 macrophages impaired NOS2 expression and inflammatory cytokine release. We also found that IRGM1 knockout (Irgm1-/-) in M1 macrophages increased Akt activation but attenuated NF-κB p65 activation, which may reveal Irgm1-mediated mechanisms of action. Interestingly, macrophage depletion in vivo inhibited Th1/Th17 differentiation in the spleen and promoted regulatory T cell (Treg) polarization in dLNs at 7 d postimmunization (dpi). Moreover, we observed that M1 macrophages in vitro promoted Th1/Th17 differentiation, which was reversed by treatment with IRGM1 small interfering RNA (siRNA), anti-TNF-α, or anti-IL-1ß mAb. These results suggest that the M1 macrophage may promote Th1/Th17 cell differentiation during the early EAE, and the proinflammatory function of M1 cells requires Irgm1.


Assuntos
Polaridade Celular , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Proteínas de Ligação ao GTP/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/patologia , Animais , Diferenciação Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Ácido Clodrônico/farmacologia , Técnicas de Cocultura , Ativação Enzimática/efeitos dos fármacos , Feminino , Inativação Gênica/efeitos dos fármacos , Heterozigoto , Lipossomos , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Regulação para Cima/efeitos dos fármacos
14.
ACS Appl Mater Interfaces ; 8(47): 32120-32131, 2016 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-27807979

RESUMO

Electrospinning is a versatile technique for the construction of microfibrous and nanofibrous structures with considerable potential in applications ranging from textile manufacturing to tissue engineering scaffolds. In the simplest form, electrospinning uses a high voltage of tens of thousands volts to draw out ultrafine polymer fibers over a large distance. However, the high voltage limits the flexible combination of material selection, deposition substrate, and control of patterns. Prior studies show that by performing electrospinning with a well-defined "near-field" condition, the operation voltage can be decreased to the kilovolt range, and further enable more precise patterning of fibril structures on a planar surface. In this work, by using solution dependent "initiators", we demonstrate a further lowering of voltage with an ultralow voltage continuous electrospinning patterning (LEP) technique, which reduces the applied voltage threshold to as low as 50 V, simultaneously permitting direct fiber patterning. The versatility of LEP is shown using a wide range of combination of polymer and solvent systems for thermoplastics and biopolymers. Novel functionalities are also incorporated when a low voltage mode is used in place of a high voltage mode, such as direct printing of living bacteria; the construction of suspended single fibers and membrane networks. The LEP technique reported here should open up new avenues in the patterning of bioelements and free-form nano- to microscale fibrous structures.

15.
Clin Immunol ; 173: 109-116, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27664932

RESUMO

MicroRNA 182 has been found to have a distinct contribution in the clonal expansion of activated- and functioning of specialized-helper T cells. In this study we knocked down microRNA 182 in vivo and induced experimental autoimmune encephalomyelitis (EAE) to determine the influences of microRNA 182 in the Treg cells functional specialization through Foxo1 dependent pathway in the peripheral lymphoid organs. Down-regulation of microRNA 182 significantly increased the proportions of Foxp3+ T cells in the peripheral lymph nodes and spleen. In vivo study verified a positive correlation between microRNA 182 levels and symptom severity of EAE, and a negative correlation between microRNA 182 and the transcriptional factor Foxp3. In vitro polarization study also confirmed the contribution of Foxo1 in microRNA 182 mediated down-regulation of Foxp3+ T cells. Together, our results provide evidence that during the development of EAE, microRNA 182 repressed Treg cells differentiation through the Foxo1 dependent pathway.


Assuntos
Encefalomielite Autoimune Experimental/imunologia , Proteína Forkhead Box O1/imunologia , MicroRNAs/imunologia , Linfócitos T Reguladores/imunologia , Animais , Diferenciação Celular , Feminino , Linfonodos/citologia , Camundongos Endogâmicos C57BL , Baço/citologia , Linfócitos T Reguladores/fisiologia
16.
Atherosclerosis ; 251: 282-290, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27439214

RESUMO

BACKGROUND AND AIMS: Atherosclerosis is a chronic inflammatory vascular disease related to macrophages uptake of low-density lipoprotein and their subsequent transformation into foam cells. M1 (inflammatory)/M2 (anti-inflammatory) balance was suggested to impact disease progression. In this study, we investigated whether the immunity related GTPase (Irgm1) regulates macrophage polarization during atherosclerosis development. METHODS: We used apolipoprotein E (ApoE) knockout and Irgm1 haplodeficient mice and induced atherosclerosis with high-cholesterol diet for the indicated months. Atherosclerotic arteries were collected from patients undergoing vascular surgery, to determine the lesional expression of Irgm1 and distribution of M1/M2 populations. RESULTS: Our results showed that IRGM/Irgm1 expression was increased in atherosclerotic artery samples (1.7-fold, p=0.0045) compared with non-atherosclerotic arteries, which was consistent with findings in the murine experimental atherosclerosis model (1.9-fold, p=0.0002). IRGM/Irgm1 expression was mostly found in lesional M1 macrophages. Haplodeficiency of Irgm1 in ApoE(-/-) mice resulted in reduced infiltrating M1 macrophages in atheroma (94%, p=0.0002) and delayed development of atherosclerotic plaques. In vitro experiments also confirmed that Irgm1 haplodeficiency reduced iNOS expression of polarized M1 macrophages (81%, p=0.0034), with negligible impact on the M2 phenotype. Moreover, we found that Irgm1 haplodeficiency in mice significantly reduced expression level of M1 function-related transcription factors, interferon regulatory factor (Irf) 5 and Irf8, but not Irf4, an M2-related transcription factor. CONCLUSIONS: This study shows that Irgm1/IRGM participates in the polarization of M1 macrophage and promotes development of atheroma in murine experimental atherosclerosis.


Assuntos
Aterosclerose/sangue , Aterosclerose/genética , Proteínas de Ligação ao GTP/fisiologia , Macrófagos/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Polaridade Celular , Colesterol/metabolismo , Feminino , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Ligação ao GTP/genética , Humanos , Fator Regulador 1 de Interferon/genética , Fatores Reguladores de Interferon/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo
17.
ISA Trans ; 64: 1-11, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27132149

RESUMO

This paper addresses the nonlinear robust tracking controller design problem for hypersonic vehicles. This problem is challenging due to strong coupling between the aerodynamics and the propulsion system, and the uncertainties involved in the vehicle dynamics including parametric uncertainties, unmodeled model uncertainties, and external disturbances. By utilizing the feedback linearization technique, a linear tracking error system is established with prescribed references. For the linear model, a robust controller is proposed based on the signal compensation theory to guarantee that the tracking error dynamics is robustly stable. Numerical simulation results are given to show the advantages of the proposed nonlinear robust control method, compared to the robust loop-shaping control approach.

18.
Inflammation ; 38(6): 2067-75, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26063186

RESUMO

We used samples from rheumatoid arthritis (RA) patients to examine whether Anti-citrullinated protein antibodies (ACPAs) alter macrophage subset distribution and promote RA development. Macrophage subset distributions and interferon regulatory factor 4 (IRF4) and IRF5 expressions were analyzed. ACPAs were purified by affinity column. After RA and osteoarthritis (OA) patients' macrophages were cocultured with ACPAs, macrophage subsets and IRF4 and IRF5 expressions were measured. Small interfering RNAs (siRNAs) were transfected into ACPA-activated cells to suppress IRF4 or IRF5. Fluorescence-activated cell sorting (FACS), Western blot, and immunohistochemistry were performed. Macrophage subset disequilibrium occurred in RA patient synovial fluids. IRF4 and IRF5 were all expressed in the synovial fluid and synovium. ACPAs (40 IU/ml) could induce macrophages to polarize to M1 subsets, and the percentage of increased M1/M2 ratio of RA patients was higher than that of the OA patients. ACPAs also induce IRF4 and IRF5 protein expressions. IRF5 siRNA transfection impaired ACPA activity significantly. We demonstrated that macrophage subset disequilibrium occurred in RA patients. ACPAs induced IRF5 activity and led to M1 macrophage polarization.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Citrulina/imunologia , Macrófagos/imunologia , Peptídeos/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Autoanticorpos/sangue , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Fatores Reguladores de Interferon/metabolismo , Macrófagos/metabolismo , Masculino , Fenótipo , Interferência de RNA , Líquido Sinovial/imunologia , Líquido Sinovial/metabolismo , Transfecção
19.
PLoS One ; 9(4): e93590, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24727667

RESUMO

Cellular behavior is strongly influenced by the architecture and pattern of its interfacing extracellular matrix (ECM). For an artificial culture system which could eventually benefit the translation of scientific findings into therapeutic development, the system should capture the key characteristics of a physiological microenvironment. At the same time, it should also enable standardized, high throughput data acquisition. Since an ECM is composed of different fibrous proteins, studying cellular interaction with individual fibrils will be of physiological relevance. In this study, we employ near-field electrospinning to create ordered patterns of collagenous fibrils of gelatin, based on an acetic acid and ethyl acetate aqueous co-solvent system. Tunable conformations of micro-fibrils were directly deposited onto soft polymeric substrates in a single step. We observe that global topographical features of straight lines, beads-on-strings, and curls are dictated by solution conductivity; whereas the finer details such as the fiber cross-sectional profile are tuned by solution viscosity. Using these fibril constructs as cellular assays, we study EA.hy926 endothelial cells' response to ROCK inhibition, because of ROCK's key role in the regulation of cell shape. The fibril array was shown to modulate the cellular morphology towards a pre-capillary cord-like phenotype, which was otherwise not observed on a flat 2-D substrate. Further facilitated by quantitative analysis of morphological parameters, the fibril platform also provides better dissection in the cells' response to a H1152 ROCK inhibitor. In conclusion, the near-field electrospun fibril constructs provide a more physiologically-relevant platform compared to a featureless 2-D surface, and simultaneously permit statistical single-cell image cytometry using conventional microscopy systems. The patterning approach described here is also expected to form the basics for depositing other protein fibrils, seen among potential applications as culture platforms for drug screening.


Assuntos
Proteínas da Matriz Extracelular/metabolismo , Citometria por Imagem/métodos , Linhagem Celular , Estudos Transversais , Gelatina/metabolismo , Humanos
20.
Genetica ; 138(11-12): 1261-70, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21104003

RESUMO

Transposon tagging is an important tool for gene isolation and functional studies. In maize, several transposon-tagging systems have been developed, mostly using Activator/Dissociation (Ac/Ds) and Mutator systems. Here, we establish another Ac-based transposon system with the donor Ac tightly linked with sugary1 (su1) on maize chromosome 4S. Newly transposed Ac (tr-Acs) were detected based on a negative dosage effect, and long-distance-transposed Ac events were identified and isolated from the donor Ac by a simple backcross scheme. In this study, we identified 208 independent long-distance-transposed Ac lines. Thirty-one flanking sequences of these tr-Acs were isolated and localized in the maize genome. As found in previous studies, the tr-Acs preferentially inserted into genic sequences. The distribution of tr-Acs is not random. In our study, the tr-Acs preferentially transposed into chromosomes 1, 2, 9 and 10. We discuss the preferential distribution of tr-Acs from Ac systems. Our system is complementary to two other Ac-based regional-mutagenesis systems in maize, and the combined use of these systems will achieve an even and high-density distribution of Ac elements throughout the maize genome for functional-genomics studies.


Assuntos
Cromossomos de Plantas/genética , Elementos de DNA Transponíveis , DNA de Plantas/genética , Genoma de Planta , Zea mays/genética , Sequência de Bases , Mapeamento Cromossômico , Clonagem Molecular , Dados de Sequência Molecular , Mutagênese Insercional , Análise de Sequência de DNA
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