Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 926
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mol Pharm ; 17(4): 1237-1247, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32129629

RESUMO

DNA vaccinations are promising strategies for treating diseases that require cellular immunity (i.e., cancer and protozoan infection). Here, we report on the use of a liposomal nanocarrier (lipid nanoparticles (LNPs)) composed of an SS-cleavable and pH-activated lipidlike material (ssPalm) as an in vivo DNA vaccine. After subcutaneous administration, the LNPs containing an ssPalmE, an ssPalm with vitamin E scaffolds, elicited a higher gene expression activity in comparison with the other LNPs composed of the ssPalms with different hydrophobic scaffolds. Immunization with the ssPalmE-LNPs encapsulating plasmid DNA that encodes ovalbumin (OVA, a model tumor antigen) or profilin (TgPF, a potent antigen of Toxoplasma gondii) induced substantial antitumor or antiprotozoan effects, respectively. Flow cytometry analysis of the cells that had taken up the LNPs in draining lymph nodes (dLNs) showed that the ssPalmE-LNPs were largely taken up by macrophages and a small number of dendritic cells. We found that the transient deletion of CD169+ macrophages, a subpopulation of macrophages that play a key role in cancer immunity, unexpectedly enhanced the activity of the DNA vaccine. These data suggest that the ssPalmE-LNPs are effective DNA vaccine carriers, and a strategy for avoiding their being trapped by CD169+ macrophages will be a promising approach for developing next-generation DNA vaccines.

2.
Sci Rep ; 10(1): 4437, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157204

RESUMO

Xanthine oxidoreductase (XOR) inhibitor administration reduces uric acid and reactive oxygen species (ROS) production, and also lowers blood pressure (BP). However, the associations of plasma XOR activity, uric acid level, and oxidative stress levels with BP remain unclear. This cross-sectional study included 156 subjects (68 males, 88 females) registered in the MedCity21 health examination registry without anti-hypertensive or anti-hyperuricemic agent administration. Plasma XOR activity was measured using our highly sensitive novel assay, which is unaffected by uric acid in the sample. BP was also determined, and serum uric acid and derivative of reactive oxygen metabolites (d-ROMs) levels were simultaneously measured. Median plasma XOR activity, serum uric acid, d-ROMs, and mean arterial pressure (MAP) values were 25.7 pmol/h/mL, 5.4 mg/dL, 305 Carr U, and 89.0 mmHg, respectively. Multiple regression analysis showed that plasma XOR activity (ß = 0.211, p = 0.019), but not serum uric acid (ß = 0.072, p = 0.502), was significantly associated with MAP. In subjects with lower but not higher d-ROMs level, an independent association of plasma XOR activity with MAP was observed (ß = 0.428, p = 0.001 and ß = 0.019, p = 0.891, respectively; p for interaction = 0.046). XOR may contribute to the pathophysiology of higher BP through ROS but not uric acid production, especially in patients with lower oxidative stress.

3.
Can J Cardiol ; 36(4): 518-526, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32007348

RESUMO

BACKGROUND: The clinical significance of left ventricular (LV) trabeculation remains unknown in cardiomyopathies. B-Type natriuretic peptide (BNP) strongly reflects LV end-diastolic wall stress and is a useful prognostic marker of cardiovascular diseases. The enhanced identification of LV trabeculae (T) with the use of cardiac magnetic resonance and the evaluation of its relationship with BNP may elucidate the biologic significance and clinical impact of trabeculation in patients with nonischemic cardiomyopathy (NICM). METHODS: The LV volume and mass of 515 patients with NICM and 36 control subjects were analyzed with the use of a steady-state free precession sequence, and individual T mass was planimetred. Major adverse cardiac events (MACE) were assessed. RESULTS: T mass index correlated with LV end-diastolic volume index (EDVI), LV mass index, and papillary muscle mass index (all P < 0.001). Also, T mass index was positively correlated with BNP level (R = 0.381; P < 0.001) and was an independent determinant of BNP after adjusting for age, sex, body mass index (BMI), etiology, LV ejection fraction, and LV EDVI (P < 0.001). Kaplan-Meier analysis during a median follow-up of 17.3 months showed that higher T mass index and increased BNP level correlated with MACE. On multivariate analysis, T mass index (P = 0.031) and BNP (P < 0.001) remained associated with poor outcomes when combined with age, sex, BMI, and etiology. CONCLUSIONS: Increased LV trabeculation was associated with LV dysfunction/remodelling and impaired outcomes in NICM of various etiologies. This may support the biologic significance of LV trabeculation and could be attributed to its association with BNP through LV wall stress.

4.
J Pharm Sci ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32070704

RESUMO

Interest has developed in the bacillus Calmette-Guerin (BCG) cell wall skeleton (BCG-CWS) as a noninfectious adjuvant. Although BCG-CWS readily undergoes aggregation, in a previous study, we applied it to cancer immunotherapy via intravenous administration by encapsulating the BCG-CWS into nanoparticles (CWS-NPs). The CWS-NPs were taken up by major histocompatibility complex (MHC) class II+ (MHC-II+) cells and induced antigen-specific cytotoxic T lymphocyte (CTL) activity. However, the nature of the contribution of MHC-II+ cells to the CTL response continues to be unclear. In this study, we investigated the relationship between the distribution of CWS-NPs in the spleen and CTL activity. The main MHC-II+ cells that internalized the CWS-NPs were B cells. Decreasing the level of polyethylene glycol modification increased the uptake of CWS-NPs by B cells, leading to an increased CTL activity. A comparison of CWS-NPs with different uptake efficiencies into dendritic cells and B cells suggested that the DCs with internalized CWS-NPs may contribute to CTL activation compared with B cells. We succeeded in enhancing CTL activity by the CWS-NPs, and the findings reported herein should provide important information regarding target cells for the development of CWS-NP.

5.
Biochem Biophys Res Commun ; 524(3): 702-709, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32035618

RESUMO

Tissue-nonspecific alkaline phosphatase (TNAP) is expressed in the calcification sites of the skeletal tissue. It promotes hydroxyapatite crystal formation by degrading inorganic pyrophosphate (PPi) and increasing inorganic phosphate (Pi) concentration. However, abnormalities in Alpl-/- mouse-derived osteoblasts are poorly understood, and the involvement of TNAP in osteoblast differentiation remains unclear. Therefore, in this study, we aimed to investigate the precise role of TNAP in osteoblast differentiation. TNAP inhibition by levamisole, a reversible TNAP inhibitor, suppressed the expression of osteoblast differentiation marker genes in wild-type osteoblastic cells. Alpl overexpression increased the expression of master osteoblast transcription factor genes runt-related transcription factor 2 (Runx2) and Sp7 and the mature osteoblast and osteocyte marker genes, bone γ-carboxyglutamate protein 2 (Bglap2) and dentin matrix protein 1 (Dmp1), respectively in Alpl-deficient osteoblastic cells. TNAP regulated Runx2 expression, which in turn regulated the expression of all other osteoblast markers, except Dmp1. Dmp1 expression was independent of RUNX2 but was dependent on extracellular Pi concentration in Runx2-deficient osteogenic cells. These results suggest that TNAP functions as an osteogenic differentiation regulator either by regulating Runx2 expression or by controlling extracellular Pi concentration.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31983315

RESUMO

To elucidate roles of the intestine in uric acid (UA) metabolism, we examined ABCG2 expression, tissue UA content and xanthine oxidoreductase (XOR) activity in different intestinal segments. Male SD rats were assigned to control group or oxonic acid-induced hyperuricemia (HUA) group. In control rats, ABCG2 was present both in villi and crypts in each segment. Tissue UA content and XOR activity were relatively high in duodenum and jejunum. However, in HUA rats, tissue UA content was significantly elevated in the ileum, whereas it remained unaltered in other segments. Moreover, ABCG2 expression in the HUA group was upregulated both in the villi and crypts of the ileum. These data indicate that the ileum may play an important role in the extra-renal UA excretion.

7.
J Diabetes Investig ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916414

RESUMO

AIMS/INTRODUCTION: Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans, unlike in rodents, and that hypoxanthine is secreted from human fat tissue. MATERIALS AND METHODS: The associations of obesity with hypoxanthine, xanthine and plasma XOR activity were investigated in 484 participants (men/women: 224/260) of the Tanno-Sobetsu Study. RESULTS: Levels of hypoxanthine, xanthine and plasma XOR activity were significantly higher in men than in women. In 59 participants with hyperuricemia, 11 (men/women: 11/0) participants were being treated with an XOR inhibitor and had a significantly higher level of xanthine, but not hypoxanthine, than that in participants without treatment. In all of the participants, hypoxanthine concentration in smokers was significantly higher than that in non-smokers. Stepwise and multivariate regression analyses showed that body mass index, smoking habit and xanthine were independent predictors of hypoxanthine after adjustment of age, sex and use of antihyperuricemic drugs. Whereas, alanine transaminase, hypoxanthine and plasma XOR activity were independent predictors for xanthine, and alanine transaminase, triglycerides and xanthine were independent predictors for plasma XOR activity. CONCLUSIONS: The concentration of hypoxanthine, but not that of xanthine, is independently associated with obesity and smoking habit, indicating differential regulation of hypoxanthine and xanthine in a general population.

8.
Mol Pharm ; 17(3): 944-953, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-31990567

RESUMO

Because the lymph node (LN) is a critical organ for inducing immune responses against pathogens and cancers, the transport of immune functional molecules such as antigens and adjuvants to LNs by delivery systems is a useful strategy for the effective outcome of an immune response. The size and charge of a delivery system largely affect the transitivity to and distribution within LN. Although pH-sensitive lipid nanoparticles (LNPs) prepared by microfluidic mixing are the latest delivery system to be applied clinically, the effects of their size and charge on the transitivity to and distribution within LN are currently unknown. We investigated the size and charge effect of LNPs prepared by microfluidic mixing on transitivity to and distribution within LNs. A 30 nm-sized LNP (30-LNP) was efficiently translocated to LNs and was taken up by CD8+ dendritic cells, while the efficiency was drastically decreased in the cases of 100 and 200 nm-sized LNPs. Furthermore, a comparative study between neutral, positively, and negatively charged 30-LNP revealed that the negative 30-LNP moved to the LN more efficiently than the other LNPs. Interestingly, the negative 30-LNP reached the deep cortex, namely, the T cell zone. Our findings provide informative insights for designing LN-targeting LNPs prepared by microfluidic mixing and for the translocation of nanoparticles in LNs.

9.
Nutrients ; 12(2)2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31991567

RESUMO

Excessive triglyceride accumulation in lipid-metabolizing tissues is associated with an increased risk of a variety of metabolic diseases. Kamishoyosan (KSS) is a Kampo composed of 10 constituent herbs, and contains moutan cortex (MC) and paeonol (PN) as the major ingredient of MC. Here, we demonstrate the molecular mechanism underlying the effect of KSS on the differentiation of mouse preadipocytes (3T3-L1 cells). KSS inhibited the accumulation of triglycerides in a dose-dependent manner in 3T3-L1 cells that were induced to differentiate into adipocytes. We also found that MC and PN were responsible for the anti-adipogenetic effect of KSS and significantly suppressed the expression of CCAAT/enhancer-binding proteins-δ (C/EBP-δ) mRNA 3 days after the induction of differentiation. Thus, PN may contribute to the anti-adipogenetic property of MC in 3T3-L1 cells. In addition, PN inhibited dexamethasone (Dex)-induced glucocorticoid receptor (GR) promoter activity. Taken together, these results suggest that PN suppresses C/EBP-δ expression by inhibiting Dex-induced GR promoter activity at the early stage of differentiation and, consequently, delays differentiation into mature adipocytes. Our results suggest that the habitual intake of Kampo-containing PN contributes to the prevention of the onset of metabolic diseases by decreasing the excessive accumulation of triglycerides in lipid-metabolizing tissues.

10.
IEEE Trans Biomed Eng ; 67(1): 203-212, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31021747

RESUMO

OBJECTIVE: Advances in sensor miniaturization and computational power have served as enabling technologies for monitoring human physiological conditions in real-world scenarios. Sleep disruption may impact neural function, and can be a symptom of both physical and mental disorders. This study proposes wearable in-ear electroencephalography (ear-EEG) for overnight sleep monitoring as a 24/7 continuous and unobtrusive technology for sleep quality assessment in the community. METHODS: A total of 22 healthy participants took part in overnight sleep monitoring with simultaneous ear-EEG and conventional full polysomnography recordings. The ear-EEG data were analyzed in the both structural complexity and spectral domains. The extracted features were used for automatic sleep stage prediction through supervized machine learning, whereby the PSG data were manually scored by a sleep clinician. RESULTS: The agreement between automatic sleep stage prediction based on ear-EEG from a single in-ear sensor and the hypnogram based on the full PSG was 74.1% in the accuracy over five sleep stage classification. This is supported by a substantial agreement in the kappa metric (0.61). CONCLUSION: The in-ear sensor is feasible for monitoring overnight sleep outside the sleep laboratory and also mitigates technical difficulties associated with PSG. It, therefore, represents a 24/7 continuously wearable alternative to conventional cumbersome and expensive sleep monitoring. SIGNIFICANCE: The "standardized" one-size-fits-all viscoelastic in-ear sensor is a next generation solution to monitor sleep-this technology promises to be a viable method for readily wearable sleep monitoring in the community, a key to affordable healthcare and future eHealth.

11.
Acta Diabetol ; 57(1): 31-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31093763

RESUMO

AIMS: Xanthine oxidoreductase (XOR) is an enzyme regulating uric acid synthesis and generation of reactive oxygen species. Several studies suggested relationship between XOR and atherosclerotic diseases; however, few previous studies have directly examined the relationship between XOR and vascular endothelial dysfunction in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the relationship between XOR activity and vascular endothelial function in patients with T1DM. METHODS: Seventy-one patients with T1DM participated in the study and underwent assessments, including plasma XOR activity and flow-mediated dilation (FMD), to measure vascular endothelial function. RESULTS: The natural logarithm value of XOR activity (ln-XOR) was 3.03 ± 0.99 pmol/h/mL, and FMD was 5.5% ± 2.4%. FMD was inversely and significantly correlated with ln-XOR (correlation coefficient: r = - 0.396, P < 0.001), UA (r = - 0.252, P = 0.034), and asymmetric dimethylarginine (ADMA) (r = - 0.414, P < 0.001). ln-XOR showed positive correlation with HbA1c (r = 0.292, P = 0.013), ALT (r = 0.658, P < 0.001), and ADMA (r = 0.363, P = 0.002). Stepwise multiple regression analysis showed that ln-XOR (standard partial regression coefficient: ß = - 0.254, P = 0.018) was an independent explanatory variable of FMD. CONCLUSIONS: The results of this study showed for the first time that XOR activity is associated with glycemic control in patients with T1DM and that XOR activity is associated with vascular endothelial dysfunction.

12.
Glob Chang Biol ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31828914

RESUMO

Robust estimates of CO2 budget, CO2 exchanged between the atmosphere and terrestrial biosphere, are necessary to better understand the role of the terrestrial biosphere in mitigating anthropogenic CO2 emissions. Over the past decade, this field of research has advanced through understanding of the differences and similarities of two fundamentally different approaches: "top-down" atmospheric inversions and "bottom-up" biosphere models. Since the first studies were undertaken, these approaches have shown an increasing level of agreement, but disagreements in some regions still persist, in part because they do not estimate the same quantity of atmosphere-biosphere CO2 exchange. Here, we conducted a thorough comparison of CO2 budgets at multiple scales and from multiple methods to assess the current state of the science in estimating CO2 budgets. Our set of atmospheric inversions and biosphere models, which were adjusted for a consistent flux definition, showed a high level of agreement for global and hemispheric CO2 budgets in the 2000s. Regionally, improved agreement in CO2 budgets was notable for North America and Southeast Asia. However, large gaps between the two methods remained in East Asia and South America. In other regions, Europe, boreal Asia, Africa, South Asia, and Oceania, it was difficult to determine whether those regions act as a net sink or source because of the large spread in estimates from atmospheric inversions. These results highlight two research directions to improve the robustness of CO2 budgets: (a) to increase representation of processes in biosphere models that could contribute to fill the budget gaps, such as forest regrowth and forest degradation; and (b) to reduce sink-source compensation between regions (dipoles) in atmospheric inversion so that their estimates become more comparable. Advancements on both research areas will increase the level of agreement between the top-down and bottom-up approaches and yield more robust knowledge of regional CO2 budgets.

13.
J Prosthodont Res ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31699614

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the fit, fracture load and aging resistance of the monolithic zirconia tooth-borne crowns with conventional and high-speed sintering. METHODS: The Y-TZP block was machined and sintered with conventional and high-speed sintering furnace. The marginal and internal gap between the crown and abutment was measured using a microscope and a fit checking material. A total of 28 crowns were further divided into an undegraded and a degraded group. An accelerated aging test was carried out on the degraded group. The crown was cemented and a fracture resistance was tested. X-ray diffraction was used to evaluate the crystalline structure. The data were analyzed with Student's t-test, and a one-way ANOVA and Tukey's multiple comparison test. RESULTS: There was no significant difference in mean marginal gap between the two groups. The mean internal gap was significantly greater in the speed sintering than in the conventional sintering (P <0.001). The mean fracture load of the conventional sintering crowns was not significantly different from that of speed sintering crowns after aging. The occurrence of monoclinic crystals of degraded crown was significantly higher than that of undegraded crown both in the conventional (P <0.001) and speed-sintering group (P <0.001). CONCLUSIONS: It was concluded that the monolithic zirconia crowns produced by high-speed sintering showed no significant difference in the marginal gap and the fracture load after aging compared to conventional sintering. Therefore, the high-speed sintering seems a valid method of producing tooth-borne monolithic zirconia crowns.

14.
ACS Omega ; 4(17): 17251-17256, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31656899

RESUMO

In this study, a simple formulation of softwood-derived glycol lignin (GL)-based epoxy resin with a high GL content of greater than 50 wt % was demonstrated by direct mixing with poly(ethylene glycol) diglycidyl ether (PEGDGE), an aliphatic epoxide, without using any solvent. Because the GL powder produced from poly(ethylene glycol) (PEG400) solvolysis of Japanese cedar softwood meal was a PEG400-modified lignin (GL400), a strong affinity between PEG counterparts facilitates the uniform mixing of GL400 with PEGDGE, and one component uncured GL400/PEGDGE epoxy resin was prepared at a relatively lower temperature (100 °C) than the curing temperature (130 °C). The epoxy curing reaction was monitored by 1H NMR and Fourier transform infrared spectroscopies. The physical and mechanical properties of the epoxy resins with different GL400 contents were then evaluated. The developed resins exhibited good flexibility and elasticity depending on the GL400 content.

15.
Int J Mol Sci ; 20(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561511

RESUMO

The organogermanium compound 3-(trihydroxygermyl)propanoic acid (THGP) has various biological activities. We previously reported that THGP forms a complex with cis-diol structures. L-3,4-Dihydroxyphenylalanine (L-DOPA), a precursor of melanin, contains a cis-diol structure in its catechol skeleton, and excessive melanin production causes skin darkening and staining. Thus, the cosmetic field is investigating substances that suppress melanin production. In this study, we investigated whether THGP inhibits melanin synthesis via the formation of a complex with L-DOPA using mushroom tyrosinase and B16 4A5 melanoma cells. The ability of THGP to interact with L-DOPA was analyzed by 1H-NMR, and the influence of THGP and/or kojic acid on melanin synthesis was investigated. We also examined the effect of THGP on cytotoxicity, tyrosinase activity, and gene expression and found that THGP interacted with L-DOPA, a precursor of melanin with a cis-diol structure. The results also showed that THGP inhibited melanin synthesis, exerted a synergistic effect with kojic acid, and did not affect tyrosinase activity or gene expression. These results suggest that THGP is a useful substrate that functions as an inhibitor of melanogenesis and that its effect is enhanced by combination with kojic acid.


Assuntos
Agaricales/enzimologia , Levodopa/química , Levodopa/farmacologia , Melaninas/biossíntese , Monofenol Mono-Oxigenase/antagonistas & inibidores , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Animais , Vias Biossintéticas/efeitos dos fármacos , Melanoma Experimental , Camundongos
16.
Rinsho Shinkeigaku ; 59(9): 592-595, 2019 Sep 25.
Artigo em Japonês | MEDLINE | ID: mdl-31474639

RESUMO

A 72-year-old man presented with continuous hyperCKemia and intermittent claudication. He exhibited no calf muscle hypertrophy at that time or afterward. Other than an increased creatine kinase (CK) level (1,525 U/l), none of the laboratory tests was abnormal, including that for myositis-related autoantibodies. Electromyography showed neurogenic changes in the left gastrocnemius. Lumbar magnetic resonance imaging revealed spinal canal stenosis (L3/4, L4/5), left L4 radiculopathy, and bilateral S1 radiculopathy. T2-weighted and short tau inversion recovery images showed high signal intensity in the bilateral biceps femoris and gastrocnemius. Histopathological evaluation of a specimen obtained from the right gastrocnemius muscle revealed neurogenic changes. The patient was diagnosed with S1 radiculopathy caused by lumbar spinal canal stenosis with hyperCKemia. Although S1 radiculopathy with hyperCKemia is usually associated with calf muscle hypertrophy, we should consider S1 radiculopathy in patients with intermittent claudication and hyperCKemia even in the absence of calf muscle hypertrophy.


Assuntos
Creatina Quinase/sangue , Radiculopatia/diagnóstico , Radiculopatia/etiologia , Idoso , Imagem de Difusão por Ressonância Magnética , Humanos , Hipertrofia , Vértebras Lombares , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Radiculopatia/diagnóstico por imagem , Estenose Espinal/complicações , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/etiologia
17.
Sci Rep ; 9(1): 13637, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541125

RESUMO

Reactive oxygen species (ROS) are very harmful to dermal cells, and it is thus important to develop cosmetics that protect the skin from ROS and other stimuli. Repagermanium is a synthetic water-soluble organogermanium polymer, and in this study, we attempted to visualize the incorporation of germanium into normal human dermal fibroblasts (NHDFs) using isotope microscopy. In addition, the content of 3-(trihydroxygermyl)propanoic acid (THGP), a hydrolyzed monomer of repagermanium, in NHDFs was determined through liquid chromatography mass spectrometry (LC-MS/MS), and the dose-dependent incorporation of THGP was confirmed. We then evaluated the preventive effects of THGP against ROS-induced NHDF death and confirmed the observed preventive effects through gene profiling and expression analysis. The addition of 0.59-5.9 mM THGP reduced cell death resulting from ROS damage caused by the reaction between xanthine oxidase and hypoxanthine and the direct addition of H2O2. Furthermore, this study provides the first demonstration that the effect of THGP was not due to the direct scavenging of ROS, which indicates that the mechanism of THGP differs from that of general antioxidants, such as ascorbic acid. The gene profiling and expression analysis showed that THGP suppressed the expression of the nuclear receptor subfamily 4 group A member 2 (NR4A2) gene, which is related to cell death, and the interleukin 6 (IL6) and chemokine (C-X-C motif) ligand 2 (CXCL2) genes, which are related to the inflammatory response. Furthermore, the production of IL6 induced by H2O2 was suppressed by the THGP treatment. Our data suggest that the preventive effect of THGP against ROS-induced cell death is not due to antioxidant enzymes or ROS scavenging.

18.
Sci Rep ; 9(1): 11335, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383907

RESUMO

Cell-based therapy using dendritic cells (DC) represents a potent cancer immunotherapy. However, activated DC express indoleamine 2,3-dioxygenase 1 (IDO1), a counter-regulatory and tolerogenic molecule, leading to the inhibition of T cell activation and the promotion of T cell differentiation into regulatory T cells. Silencing the IDO1 gene in DC by small interfering RNA (siRNA) represents a potent therapeutic strategy. We report on the successful and efficient introduction of a siRNA targeting IDO1 into mouse DCs by a means of a multifunctional envelope-type nanodevice (MEND) containing a YSK12-C4 (YSK12-MEND). The YSK12-C4 has both fusogenic and cationic properties. The YSK12-MEND induced an effective level of gene silencing of IDO1 at siRNA doses in the range of 1-20 nM, a concentration that commercially available transfection reagents are not able to silence. The YSK12-MEND mediated IDO1 silencing had no effect on the characteristic determinants of DC phenotype such as CD11c, CD80 and MHC class II. The silencing of IDO1 in DC by the YSK12-MEND significantly enhanced the antitumor effect against E.G7-OVA tumor. Moreover, a decrease in the numbers of regulatory T cells in the tumor was observed in mice that were treated with the IDO1-silenced DC. The YSK12-MEND appears to be a potent delivery system for IDO1-silenced DC based cancer immunotherapy.

19.
J Biophotonics ; 12(12): e201960028, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31407507

RESUMO

A fluorescence background is one of the common interference factors of the Raman spectroscopic analysis in the biology field. Shifted-excitation Raman difference spectroscopy (SERDS), in which a slow (typically 1 Hz) modulation to excitation wavelength is coupled with a sequential acquisition of alternating shifted-excitation spectra, has been used to separate Raman scattering from excitation-shift insensitive background. This sequential method is susceptible to spectral change and thus is limited only to stable samples. We incorporated a fast laser modulation (200 Hz) and a mechanical streak camera into SERDS to effectively parallelize the SERDS measurement in a single exposure. The developed system expands the scope of SERDS to include temporary varying system. The proof of concept is demonstrated using highly fluorescent samples, including living algae. Quantitative performance in fluorescence rejection and the robustness of the method to the dynamic spectral change during the measurement are manifested.

20.
Plast Reconstr Surg Glob Open ; 7(5): e2205, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31333938

RESUMO

Background: This multicenter study aimed to examine the reasons for prosthesis rejection and assess the quality of life (QOL) among patients with upper limb deficiency. Methods: Three rehabilitation centers in Japan and 1 academic medical center in the United States participated. Patients between the age of 12 and 75 years with unilateral or bilateral upper limb absence from the level of wrist to shoulder disarticulation were included. Two questionnaires were used, an original questionnaire on prosthesis use and the EQ-5D, which were completed by both the participant and a live-in proxy. Results: Of the 367 patients with upper limb loss invited, 174 patients participated in this study. Eighty percent of the study population were male patients. The most common amputation level was transradial. Trauma was the most common cause of limb loss. The prosthesis rejection rate was 9% (n = 16). The most common reason for abandonment was a lack of prosthesis functionality. Ten of 16 prosthesis nonusers (63%) and 59 prosthesis users (38%) were unemployed or students. The mean EQ-5D utility score was significantly higher in prosthesis users than in nonusers (0.762 versus 0.628, P < 0.01). Live-in proxies significantly overestimated QOL in male patients (0.77 versus 0.807, P=0.01). Conclusions: The current prosthesis rejection rate is low. QOL was significantly higher in prosthesis users than in nonusers. More prosthesis users were employed compared with nonusers. Care should be taken not to overestimate the QOL of male patients with upper limb loss as their proxies often did.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA