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1.
Int J Biol Macromol ; 263(Pt 1): 130293, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382791

RESUMO

Cellulose nanocrystal (CNC) film is known to be one kind of dynamic color-sensing material, capable of reversible color changes in response to varying humidity levels. However, the brittleness, low hygroscopicity and poor homogeneity of these films have hindered their development. To address this limitation, we present a novel approach where we combine natural deep eutectic solvents (NADES) with sorbitol under the influence of circular shear flow to craft a CNC humidity-sensitive film with enhanced flexibility, hygroscopicity and homogeneity. The inclusion of sorbitol and NADES enhances hygroscopicity and improves the flexibility. Surprisingly, the introduction of circular shear flow was found not only to improve homogeneity, macroscopically and microscopically, but also to further enhance flexibility, toughness, and water absorption capability. The resulting composite films demonstrated highly reversible color changes across the whole visible spectrum depending on the relative humidity, showing their capability to be reliable humidity-sensing materials. Thanks to the improved homogeneity and flexibility, the obtained humidity-sensing composite film can be employed in its entirety without the need for cutting, making it a promising candidate for various applications.


Assuntos
Celulose , Nanopartículas , Celulose/química , Umidade , Nanopartículas/química , Molhabilidade , Sorbitol
2.
Front Nutr ; 11: 1355116, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414486

RESUMO

This study employed mixed bacterial strains to ferment seabuckthorn seed meal into peptides, and conducted a comprehensive evaluation of the growth adaptive conditions, molecular weight distribution, volatile compounds, and in vitro hypoglycemic activity required for fermentation. Results showed that when the amount of maltose was 1.1% and MgSO4·7H2O was added at 0.15 g/L, the peptide yield reached 43.85% with a mixed fermentation of Lactobacillus fermentum, Bacillus subtilis, Lactobacillus casei, Lactobacillus rhamnosus, and Lactobacillus acidophilus. Components with a molecular weight below 1 kDa were found to be more effective in inhibiting the activity of α-amylase and α-glucosidase, with the identified sequence being FYLPKM. Finally, SPME/GC-MS results showed that 86 volatile components were detected during the fermentation of seabuckthorn seed meal, including 22 alcohols, 9 acids, 7 ketones, 14 alkanes, 20 esters, and 14 other compounds. With prolonged fermentation time, the content of acids and esters increased significantly.

3.
Food Chem X ; 20: 101029, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38144770

RESUMO

This study assessed the impact of milk on the bioactive compounds, physicochemical properties, antioxidant activity, ROS inhibition, and volatile flavor compounds of fermented black mulberry juice (FBMJ). Firstly, the results showed that 25% concentration of milk was the most suitable for preparing FBMJ-Milk. Compared to the control group, the addition of milk significantly increased the SOD activity and antioxidant capacity, as well as enhanced the total phenolic content (TPC) and SOD storage stability. Secondly, HS-SPME-GC-MS combined with OPLS-DA analysis identified 49 compounds in FBMJM, including 12 esters, 6 acids, 1 ketone, 2 aldehydes, 19 alcohols and 9 other compounds. During the storage, the levels of ethyl ester compounds decreased significantly, while the degradation of ester produced some acid and alcohol compounds. The findings revealed that the addition of milk was beneficial for maintaining the antioxidant stability of FBMJM during storage and enhancing the richness of product flavor.

4.
Int J Biol Macromol ; 235: 123805, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36863669

RESUMO

Photonic crystal materials based on cellulose nanocrystals (CNC), which are environmentally responsive and green, have attracted widespread attention. To overcome the brittleness of CNC films, many researchers have explored functional additives to improve their performance. In this study, a new green deep eutectic solvents (DESs) and an amino acid-based natural deep eutectic solvents (NADESs) were introduced into CNC suspensions for the first time, and hydroxyl-rich small molecules (glycerol, sorbitol) and polymers (polyvinyl alcohol, polyethylene glycol) were coassembled with the DESs and NADESs to form three-component composite films. The CNC/G/NADESs-Arg three-component film reversibly changed color from blue to crimson as the relative humidity rose from 35 % to 100 %; additionally, the elongation at break increased to 3.05 %, and the Young's modulus decreased to 4.52 GPa. The hydrogen bond network structure provided by trace amounts of the DESs or NADESs not only improved the mechanical properties of the composite films but also increased their water absorption capacities without destroying their optical activities. This allows for the development of more stable CNC films and creates potential for biological applications in the future.


Assuntos
Celulose , Nanopartículas , Celulose/química , Solventes Eutéticos Profundos , Umidade , Nanopartículas/química , Polímeros , Solventes/química
5.
Environ Pollut ; 293: 118489, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780754

RESUMO

Detecting pesticide residues in human serum is a challenging process due to trace-level chronic exposure. Several methods using magnetic adsorbents have been developed for analyzing pesticide residue levels in human serum, but it is still difficult to achieve lower quantitative levels, and the adsorption mechanism for extracting pesticides is unclear. Herein, we propose a feasibility concept of using C18-functionalized magnetic nanoparticles for the adsorption of target pesticides, focusing on the extensively used weakly polar pesticides based on molecular dynamics (MD) simulations. To support this, the facilitated target nanoparticles of Fe3O4@SiO2-C18 were synthesized at a size of 12-13 nm with a magnetic saturation of 40 emu/g. After optimizing and establishing the extraction conditions (1.8 mL C18 modifier, 10 mg sorbents, 3 min adsorption time, 1000 µL ACN for desorption eluent at pH 3.8 and 5 min desorption time), which exhibited recovery = 72.3%-118.3% with RSDs = 0.03-6.57, linearity at 0.01-10 ng/mL with R2 = 0.9561-0.9993, and LODs = 0.01-0.30 ng/mL for the 11 weakly polar pesticides in human serum. Furthermore, the mechanism by which the C18 group selectively extracts weakly polar pesticides was confirmed by binding van der Waals and electrostatic interactions under stable and strong binding energy. The extraction process of efficient adsorption and desorption with C18 functional magnetite nanoparticles suggests a simple method for detecting weakly polar pesticides. The concept may lead to a general approach to analyzing multiple pesticide residues in human serum at trace levels.


Assuntos
Nanopartículas de Magnetita , Resíduos de Praguicidas , Praguicidas , Cromatografia Líquida de Alta Pressão , Humanos , Simulação de Dinâmica Molecular , Resíduos de Praguicidas/análise , Praguicidas/análise , Dióxido de Silício , Extração em Fase Sólida , Espectrometria de Massas em Tandem
6.
Chemosphere ; 282: 131120, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34470165

RESUMO

This study evaluated the adverse effects of low-dose imidacloprid (IMI) on the characteristics of sperm from male Wistar rats. Thirty mature male rats were equally divided into three groups and orally administered vehicle (Control Group), acceptable daily intake (ADI) concentration of IMI (Group 1), and IMI at a dose 10-fold that of the ADI (Group 2) for 90 days. The findings revealed that IMI caused abnormalities in sperm concentrations and morphologies, accompanied by an imbalance of the gonadal hormone testosterone. Histopathological damage and decrease of testosterone levels were observed in testes from rats treated with IMI. However, estradiol and gonadotropin levels were unchanged after IMI treatment. IMI inhibited the activity of cytochrome P450 3A4 (CYP3A4) and left itself existed in the organism of rats. The indicators relating to sperms and CYP3A4 activity were recovered when rats were co-treated with IMI and CYP3A4 inducer rifampicin together. These results indicated that low-dose IMI exposure caused sperm abnormalities through affecting on the spermiogenesis in testis. Inhibition of CYP3A4 activity by IMI largely contributed to its sperm toxicity. Thus, IMI exposure at doses close to real-world settings resulted in sperm toxicity on rats, which might be a potential risk factor for human reproductive diseases.


Assuntos
Citocromo P-450 CYP3A , Espermatogênese , Animais , Masculino , Neonicotinoides/toxicidade , Nitrocompostos , Ratos , Ratos Wistar , Espermatozoides , Testículo , Testosterona
7.
Waste Manag Res ; 39(1): 63-72, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32972328

RESUMO

With increasing population and urbanization levels in the People's Republic of China, environmental problems related to the management of municipal solid waste (MSW) are inevitable. This study aimed to determine the environmental impact of the current MSW management system in Hohhot City and to establish an optimum future strategy for it by applying life cycle assessment (LCA) methodology. Four scenarios were compared using the CML-IA impact characterization method, which took into account their potential contribution to global warming, ozone depletion, human toxicity, photochemical ozone creation, acidification, and eutrophication potentials. The system boundaries included the collection and recycling, transfer and transportation of MSW, and its disposal by incineration, landfilling, and carbon dioxide (CO2) capture methods. The results showed that the scenario involving landfill and incineration in a ratio of 1:5 was the optimal waste management option; however, increasing the proportion of waste incinerated led to a significant increase in global warming potential. Additional technologies are thus required to overcome this problem, and it was found that the use of CO2 capture technology resulted in a 30% reduction in the total environmental impact potential. This study's results indicate that LCA is a valuable and practical tool to support decision-making that can be used to suggest problematic areas in current waste management strategies and to determine an optimal alternative to the solid waste management option.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Animais , China , Cidades , Humanos , Incineração , Estágios do Ciclo de Vida , Resíduos Sólidos/análise
8.
J Immunol ; 206(2): 422-431, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33288543

RESUMO

Fibroblast-like synoviocytes (FLS), one of the main cell types of the rheumatoid arthritis (RA) synovium, possess phenotypic and molecular characteristics of transformed cells. JQ1, an inhibitor of the bromodomain and extra terminal domain family that includes BRD2, BRD3, BRD4, and BRDt, has shown efficacy in models of arthritis. We demonstrate that the active isomer of JQ1 but not its inactive isomer inhibits IL-1ß-induced RA-FLS activation and proliferation. To understand the mechanism of JQ1 action, we subjected JQ1-treated RA-FLS to transcriptional profiling and determined BRD2 and BRD4 cistromes by identifying their global chromatin binding sites. In addition, assay for transposable accessible chromatin by high throughput sequencing was employed to identify open and closed regions of chromatin in JQ1-treated RA-FLS. Through an integrated analysis of expression profiling, Brd2/Brd4 cistrome data, and changes in chromatin accessibility, we found that JQ1 inhibited key BRD2/BRD4 superenhancer genes, downregulated multiple crucial inflammatory pathways, and altered the genome-wide occupancy of critical transcription factors involved in inflammatory signaling. Our results suggest a pleiotropic effect of JQ1 on pathways that have shown to be individually efficacious in RA (in vitro, in vivo, and/or in humans) and provide a strong rationale for targeting BRD2/BRD4 for disease treatment and interception.

9.
J Sep Sci ; 43(17): 3534-3545, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32618409

RESUMO

Detecting pesticide residues in human serum is a challenging process. In this study we developed and validated a method for the extraction and recovery of residues of multiple classes of pesticides from serum using one reagent. Salt-assisted acetonitrile extraction and high-performance liquid chromatography with quadrupole time of flight tandem mass spectrometry were used to quantitate 34 pesticides classified in nine groups of chemicals in human serum samples, which are frequently detected in food. The recoveries for 33 of analyzed pesticides ranged from 86 to 112% with relative standard deviations below 15%. The limits of quantitation and linearity of 31 of the pesticides were 1 µg/L and >0.990, respectively. The lower limit of quantitation has been reported in the literature particularly for multi-classes pesticide mixtures in human serum. The salt-acetonitrile reagent was allowed to achieve good recoveries and detection limits, which could be attributed to salt altering the solvent polarity, preferentially collecting the organic phase in the solution, and promoting the extraction. The developed method was applied for two organophosphate pesticide metabolites, diethylphosphate and 3,5,6-trichloro-2-pyridinol, in serum from rats that were fed a nonlethal quantity of chlorpyrifos. The concentrations of these two were 252.18 ± 15.47 and 0.63 ± 0.23 µg/L, respectively.


Assuntos
Acetonitrilas/química , Compostos Organofosforados/sangue , Resíduos de Praguicidas/sangue , Praguicidas/sangue , Cromatografia Líquida de Alta Pressão , Humanos , Sais/química , Espectrometria de Massas em Tandem
10.
Sci Total Environ ; 726: 138496, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32481206

RESUMO

Similar to diethylphosphate (DEP), 3,5,6-trichloro-2-pyridinol (TCP) is also a characteristic chemical substance and ultimate transformation product of chlorpyrifos (CPF) because the structure of TCP is equivalent to the trichloro pyridine structure of CPF. TCP is often used as a biomarker of CPF exposure. TCP and DEP are often detected in human blood and urine due to the widespread use of CPF. No studies have sufficiently clarified which structure contributes to the negative effect of CPF on testosterone synthesis. This study aims to explain which structure promotes the inhibitory effect of CPF on testosterone synthesis and the related influence mechanisms. After 20 weeks of exposure, the testosterone level in testes was significantly reduced by different doses of CPF (0.3 mg/kg body weight CPF and 3.0 mg/kg body weight CPF). Meanwhile, the level of testosterone synthesized by isolated primary Leydig cells was also reduced by CPF. In addition, TCP but not DEP aggravated the decrease in testosterone synthesis in isolated primary Leydig cells. On the other hand, CPF and TCP significantly decreased the levels of the Star protein, CREB phosphorylation and PKA phosphorylation, which are important in regulating testosterone synthesis. Based on these results, TCP is a key structure that mediates the CPF-induced decrease in testosterone synthesis by terminating the signal transmission of the LH-LHR-PKA-CREB-Star pathway. Thus, chemicals with the TCP structure may be potential endocrine disruptors that decrease fertility. Chemicals that can be converted to TCP or achieve a trichloro pyridine structure must be considered during reproductive toxicity risk assessment.


Assuntos
Clorpirifos , Inseticidas , Humanos , Masculino , Piridinas , Piridonas , Testosterona
11.
Sensors (Basel) ; 20(4)2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32075121

RESUMO

Time difference of arrival (TDoA) technology is widely utilized for source localization, which stimulates many studies on performance-evaluation approaches for TDoA localization systems. Some approaches using simulations are designed merely for a simple Line-of-Sight (LoS) scenario while some other ones using experiments show high cost and inefficiency. This paper proposes an integrated approach to evaluate a TDoA localization system in an area with a complicated environment. Radio propagation graph is applied through a simulation to obtain channel impulse responses (CIRs) between a source to be located and the TDoA sensors for the area. Realistic signals received by the sensors in baseband are emulated combining the source transmitted signal and the CIRs. A hardware unit takes charge of sending the radio emulated received signals to the system under test, which is consistent with real experimental measurements. Statistical analysis of the system is allowed based on localization errors obtained comparing the system's estimates with the ground truth of the source location. Verified results for LoS and non-LoS scenarios with variable transmitted signal bandwidths and signal-to-noise ratios, as well as for three variations of the sensor locations in an automobile circuit, show the usability of the proposed experiment-free performance-evaluation approach.

12.
Mol Microbiol ; 111(1): 131-144, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30276893

RESUMO

In response to low levels of magnesium (Mg2+ ), the PhoQP two component system induces the transcription of two convergent genes, one encoding a 31-amino acid protein denoted MgtS and the second encoding a small, regulatory RNA (sRNA) denoted MgrR. Previous studies showed that the MgtS protein interacts with and stabilizes the MgtA Mg2+ importer to increase intracellular Mg2+ levels, while the MgrR sRNA base pairs with the eptB mRNA thus affecting lipopolysaccharide modification. Surprisingly, we found overexpression of the MgtS protein also leads to induction of the PhoRB regulon. Studies to understand this activation showed that MgtS forms a complex with a second protein, PitA, a cation-phosphate symporter. Given that the additive effect of ∆mgtA and ∆mgtS mutations on intracellular Mg2+ concentrations seen previously is lost in the ∆pitA mutant, we suggest that MgtS binds to and prevents Mg2+ leakage through PitA under Mg2+ -limiting conditions. Consistent with a detrimental role of PitA in low Mg2+ , we also observe MgrR sRNA repression of PitA synthesis. Thus, PhoQP induces the expression of two convergent small genes in response to Mg2+ limitation whose products act to modulate PitA at different levels to increase intracellular Mg2+ .


Assuntos
Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Magnésio/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Transporte de Fosfato/metabolismo , Pequeno RNA não Traduzido/metabolismo , Escherichia coli/genética , Redes Reguladoras de Genes
13.
J Cell Biochem ; 119(11): 8897-8908, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30105826

RESUMO

As a common cause of shoulder pain and disability, rotator cuff injury (RCI) represents a debilitating condition affecting an individual's quality of life. Although surgical repair has been shown to be somewhat effective, many patients may still suffer from reduced shoulder function. The aim of the current study was to identify a more effective mode of RCI treatment by investigating the effect of platelet-derived growth factor subunit B (PDGF-B) on tendon-bone healing after RCI repair by modifying bone marrow-derived mesenchymal stem cells (BMSCs). Surface markers of BMSCs were initially detected by means of flow cytometry, followed by establishment of the rat models and construction of the lentiviral vector. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assay, alizarin red staining, and oil red O staining were used to provide verification that PDGF-B was indeed capable of promoting BMSC viability, osteogenic and adipogenic differentiation capability. Furthermore, biomechanical assessment results indicated that PDGF-B could increase the ultimate load and stiffness of the tendon tissue. Real-time reverse-transcription quantitative polymerase chain reaction and Western blot analysis methods provided evidence suggesting that PDGF-B facilitated the expression of tendon-bone healing-related genes and proteins, while contrasting results were obtained after PDGF-B silencing. Taken together, the key findings of the current study provided evidence suggesting that overexpressed PDGF-B could act to enhance tendon-bone healing after RCI repair, thus highlighting the potential of the functional promotion of PDGF-B as a future RCI therapeutic approach.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Proteínas Proto-Oncogênicas c-sis/genética , Proteínas Proto-Oncogênicas c-sis/fisiologia , Lesões do Manguito Rotador/reabilitação , Tendões/fisiologia , Cicatrização/fisiologia , Adipogenia/fisiologia , Análise de Variância , Animais , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Expressão Ectópica do Gene/genética , Regulação da Expressão Gênica , Vetores Genéticos , Lentivirus/genética , Masculino , Osteogênese/fisiologia , Ratos , Ratos Sprague-Dawley , Transfecção
14.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1093-1094: 174-182, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30032017

RESUMO

Resveratrol, as one of the stilbenoids, is present in abundance in wine grapes and has been shown to selectively quench 1O2. DNA is oxidized by 1O2 causing irreparable functional damage, and of the nucleic acids, guanine is the most susceptible. An agarose gel electrophoresis assay demonstrated that DNA was damaged by 1O2 with less than 5 min of UVA irradiation, and also that 5 mM resveratrol dissolved in MeOH could relieve the observed oxidation stress. Ultra-high performance liquid chromatography coupled with mass spectrometry was performed to reveal the mechanism. Four guanine oxidation products at m/z 140.0334 [M-H]-(1), DGh, 8-oxoG, Sp and two conjugates at m/z 377.1104 [M-H]- and 391.0907 [M-H]- were identified and quantified. Thus, we propose the mechanism that the phenol ring of resveratrol links with the free amino groups (NH) of guanine at the beginning of 1O2 attack to form m/z 377.1104 [M-H]-, however, as 1O2 is able to attack the amino groups continuously, resveratrol can efficiently react with 1O2 prior to damage, and form m/z 391.0907 [M-H]- thereby protecting guanine.


Assuntos
Antioxidantes/química , Guanina/química , Oxirredução/efeitos dos fármacos , Estilbenos/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , DNA/efeitos dos fármacos , Espectrometria de Massas/métodos , Modelos Moleculares , Plasmídeos , Resveratrol , Estilbenos/farmacologia
15.
Arthritis Res Ther ; 20(1): 85, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29720240

RESUMO

BACKGROUND: Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. METHODS: RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target. RESULTS: We demonstrated that the plasma cell/plasmablast-related genes CD38, XBP1, IRF4, PRDM1, IGJ and TNFSF13B are significantly up-regulated in synovial biopsies from patients with arthralgia, undifferentiated arthritis (UA), early RA and established RA as compared to healthy controls and control patients with osteoarthritis. In addition, the highest CD38 expression was observed on plasma cells and plasmablasts compared to natural killer (NK) cells, classical dendritic cells (DCs), plasmacytoid DCs (pDCs) and T cells, in blood from healthy controls and patients with SLE and RA. Furthermore, IHC showed CD38 staining in the same region as CD3 and CD138 staining in synovial tissue biopsies from patients with early RA. Most importantly, our data show for the first time that daratumumab effectively depletes plasma cells/plasmablasts in PBMC from patients with SLE and RA in a dose-dependent manner ex vivo. CONCLUSION: These results indicate that CD38 may be a potential target for RA disease interception and daratumumab should be evaluated clinically for the treatment of both RA and SLE.


Assuntos
ADP-Ribosil Ciclase 1/antagonistas & inibidores , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Plasmócitos/metabolismo , ADP-Ribosil Ciclase 1/genética , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Idoso , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Células Cultivadas , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia
16.
PLoS One ; 13(2): e0192704, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29489833

RESUMO

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.


Assuntos
Artrite Reumatoide/patologia , Regulação para Baixo , Receptor de Morte Celular Programada 1/metabolismo , Membrana Sinovial/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Membrana Sinovial/metabolismo
17.
PLoS One ; 12(9): e0183928, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28863153

RESUMO

OBJECTIVES: This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown. METHODS: Paired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing. RESULTS: Large differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function. CONCLUSIONS: We have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Membrana Sinovial/efeitos dos fármacos , Linfócitos T/citologia , Adulto , Idoso , Artroscopia , Biópsia , Estudos de Casos e Controles , Diferenciação Celular , Regulação para Baixo , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Plasmócitos/citologia , Análise de Componente Principal , Indução de Remissão , Análise de Sequência de RNA , Sulfassalazina/uso terapêutico , Membrana Sinovial/metabolismo , Linfócitos T/efeitos dos fármacos , Transcriptoma
18.
Food Chem ; 237: 1101-1111, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28763956

RESUMO

Stilbenoids, in particular, resveratrol and its dimers are abundantly present in Vitis vinifera and proved to be quenchers with selective singlet oxygen. However, only a few mechanisms are reported for their complex molecular architectures. Hence, UHPLC combined with accurate MS is employed to investigate the photo-radiation mechanism of resveratrol dimers systematically. Ⅰ: Resorcinol ring exists in Scirpusin A 1, Trans-ε-viniferin 2 and Trans-σ-viniferin 3. The photochemical products were 14Da or 16Da higher than reagents and underwent an endoperoxide intermediate to quinones; Ⅱ: [2+2] cyclization of intra-molecular trans-double bond. The products were 18Da greater than substrates thereby cycloaddited to oxygen heterocyclic; Ⅲ : [4+1], [4+2] cyclization of oxetane formed products were 28Da and 44Da higher than 3, 2 and 1. Ⅳ : 5-phenol-2,3-dihydrobenzofuran ring exists in 2 been oxidized, causing the products at 16Da, 32Da higher than 2. This is the first to reveal the generally regular mechanism of stilbenoids quenching singlet oxygen.


Assuntos
Estilbenos/análise , Benzofuranos , Isomerismo , Resveratrol , Oxigênio Singlete , Estilbenos/química
19.
Mater Sci Eng C Mater Biol Appl ; 78: 452-456, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28576008

RESUMO

The present work showed the biofabrication of platinum nanoparticles (PtNPs) using chondroitin sulfate via a facile, eco-friendly route by just heating leaf extract and H2PtCl6·6H2O (Chloroplatinic acid) solution which gave a brown-colored PtNPs dispersion. The assynthesized PtNPs were analyzed by using Transmission electron microscopy (TEM), Energy dispersive spectroscopy (EDX), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and Selected area electron diffraction (SAED). TEM analysis showed PtNPs of irregular shape with a size existed in the range from 3 to 5nm. From zeta potential studies it is found the surface charge of the synthesized PtNPs is negative (-25.6mV). FTIR analysis and zeta potential measurements of PtNPs confirm the capping of chondroitin sulfate onto the surface of nanoparticles. XRD and SAED pattern revealed the crystalline nature of synthesized nanoparticles. Further, the in-vitro cytotoxicity of PtNPs against the osteoarthritis chondrocytes showed their biocompatibility, hence the obtained nanoparticles may have future scope in the treatment of osteoarthritis. Also, the present approach is green alternative to the traditionally available chemical methods that are currently been used now a days using chemical reagents such that are hazardous to human and environment.


Assuntos
Sulfatos de Condroitina/química , Humanos , Nanopartículas Metálicas , Osteoartrite , Platina , Difração de Raios X
20.
Proc Natl Acad Sci U S A ; 114(22): 5689-5694, 2017 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-28512220

RESUMO

Synthesis of the 31-amino acid, inner membrane protein MgtS (formerly denoted YneM) is induced by very low Mg2+ in a PhoPQ-dependent manner in Escherichia coli Here we report that MgtS acts to increase intracellular Mg2+ levels and maintain cell integrity upon Mg2+ depletion. Upon development of a functional tagged derivative of MgtS, we found that MgtS interacts with MgtA to increase the levels of this P-type ATPase Mg2+ transporter under Mg2+-limiting conditions. Correspondingly, the effects of MgtS upon Mg2+ limitation are lost in a ∆mgtA mutant, and MgtA overexpression can suppress the ∆mgtS phenotype. MgtS stabilization of MgtA provides an additional layer of regulation of this tightly controlled Mg2+ transporter and adds to the list of small proteins that regulate inner membrane transporters.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Magnésio/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana/genética , ATPases do Tipo-P/metabolismo
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