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1.
Macromolecules ; 56(16): 6247-6255, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37637306

RESUMO

Nematic liquid crystal elastomers (LCEs) have anomalously high vibration damping, and it has been assumed that this is the cause of their anomalously high-pressure-sensitive adhesion (PSA). Here, we investigate the mechanism behind this enhanced PSA by first preparing thin adhesive tapes with LCE of varying cross-linking densities, characterizing their material and surface properties, and then studying the adhesion characteristics with a standard set of 90° peel, lap shear, and probe tack tests. The study confirms that the enhanced PSA is only present in (and due to) the nematic phase of the elastomer, and the strength of bonding takes over 24 h to fully reach its maximum value. Such a long saturation time is caused by the slow relaxation of local stress and director orientation in the nematic domains after pressing against the surface. We confirm this mechanism by showing that freshly pressed and annealed tape reaches the same maximum bonding strength on cooling, when the returning nematic order is forming in its optimal configuration in the pressed film.

2.
Sci Rep ; 13(1): 10035, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340069

RESUMO

The effect of elastomeric damping pads, softening the collision of hard objects, is investigated comparing the reference silicone elastomer and the polydomain nematic liquid crystalline elastomer, which has a far superior internal dissipation mechanism. We specifically focus not just on the energy dissipation, but also on the momentum conservation and transfer during the collision, because the latter determines the force exerted on the target and/or the impactor-and it is the force that does the damage during the short time of an impact, while the energy might be dissipated on a much longer time scale. To better assess the momentum transfer, we compare the collision with a very heavy object and the collision with a comparable mass, when some of the impact momentum is retained in the target receding away from the collision. We also propose a method to estimate the optimal thickness of an elastomer damping pad for minimising the energy in impactor rebound. It has been found that thicker pads introduce a large elastic rebound and the optimal thickness is therefore the thinnest possible pad that does not suffer from mechanical failure. We find good agreement between our estimate of the minimal thickness of the elastomer before the puncture through occurs and the experimental observations.

3.
Plant J ; 113(5): 1080-1094, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36625794

RESUMO

Seed longevity is an important trait for agriculture and the conservation of genetic resources. ß-1,3-Glucanases were first recognized as pathogenesis-related proteins involved in plant defense, but their roles in seeds are largely unknown. Here, we report a glycosylphosphatidylinositol-anchored ß-1,3-glucanase, BG14, that degrades callose in seed embryos and functions in seed longevity and dormancy in Arabidopsis. The loss of function of BG14 significantly decreased seed longevity, whereas functional reversion (RE) and overexpression (OE) lines reversed and increased the impaired phenotype, respectively. The loss of function of BG14 enhanced callose deposition in the embryos of mature seeds, confirmed by quantitative determination and the decreased callose degrading ability in bg14. The drop-and-see (DANS) assay revealed that the fluorescence signal in bg14 was significantly lower than that observed in the other three genotypes. BG14 is located on the periphery of the cell wall and can completely merge with callose at the plasmodesmata of epidermal cells. BG14 was highly expressed in developing seeds and was induced by aging and abscisic acid (ABA). The loss of function of BG14 led to a variety of phenotypes related to ABA, including reduced seed dormancy and reduced responses to treatment with ABA or pacolblltrazol, whereas OE lines showed the opposite phenotype. The reduced ABA response is because of the decreased level of ABA and the lowered expression of ABA synthesis genes in bg14. Taken together, this study demonstrated that BG14 is a bona fide BG that mediates callose degradation in the plasmodesmata of embryo cells, transcriptionally influences ABA synthesis genes in developing seeds, and positively affects seed longevity and dormancy in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Dormência de Plantas/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Longevidade , Germinação/genética , Ácido Abscísico/metabolismo , Sementes/metabolismo , Regulação da Expressão Gênica de Plantas
4.
Sci Total Environ ; 854: 158737, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36108860

RESUMO

Groundwater is a key water resource in alpine watersheds, but its quality is deteriorating due to human activities. The Golmud River watershed is a representative alpine watershed in Northwest China, and it was chosen to explore groundwater chemistry, associated controlling factors, source contributions, and potential health risks. The analysis includes the use of a self-organizing map (SOM), positive matrix factorization (PMF), ionic ratios, and a Monte Carlo simulation. The content of total dissolved solids in phreatic water was higher in the dry season and increased from the mountainous zone to the fine-soil plain-overflowing zone. Additionally, the water type varied from HCO3- to Cl- types whereas confined groundwater was chemically stable and of a HCO3- type. The SOM results showed a visual correlation between the ions in groundwater. The combination of SOM, PMF, and ionic ratios identified water-rock action as a dominant factor of groundwater chemistry. It was also found that Clusters I and III were mainly influenced by silicate weathering (a total contribution of 38.4 %), whereas evaporation was dominant in Cluster VI (a contribution of 32.5 %). Anthropogenic pollution was mainly associated with clusters V and IV and was related to industrial and agricultural activities during the snowmelt and wet seasons, and fluorine deposition formed by residential coal heating during the dry season (contributions of 1.4 % and 23.8 % in Clusters V and IV, respectively). The sudden increases in B3+ and Li+ in Cluster II were due to inputs from small tributaries (a contribution of 3.9 %). The probabilistic health risk assessment showed that fluoride posed a greater non-carcinogenic risk to human health than Sr2+, B3+, and NO3-, and its potential threat to children was more significant during the dry season than in other seasons. It is necessary for local governments to establish urgent fluoride emission control policies within the Golmud River watershed.

5.
Molecules ; 27(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36500568

RESUMO

In this study, 1-methylhydantoin cinnamic imides were synthesized from 1-methylhydantoin and trans-cinnamic acid, and their anti-inflammatory activity was investigated. The anti-inflammatory activity in vitro was evaluated by measuring the contents of NO, TNF-α and IL-1ß in the supernatant of RAW264.7 cells stimulated by LPS. The cytotoxicity of 1-methylhydantoin cinnamoyl imides on RAW264.7 cells was detected using the CCK-8 method. The results showed that compounds 2 and 4 can significantly inhibit the release of NO and reduce the secretion of TNF-α and IL-1ß. Compound 3 inhibited the production of TNF-α. The inhibition rate of COX was evaluated in vitro. The in vivo anti-inflammatory activities of the five compounds were evaluated by establishing an animal model of xylene ear swelling. The results showed that 1-methylhydantoin cinnamic imides could alleviate xylene-induced ear edema in mice in a dose-dependent manner. Among them, the effect of compound 5 was the most significant. Under the action of high dosage, its ear swelling inhibition rate was as high as 52.08%.


Assuntos
Imidas , Fator de Necrose Tumoral alfa , Camundongos , Animais , Fator de Necrose Tumoral alfa/efeitos adversos , Imidas/uso terapêutico , Extratos Vegetais/farmacologia , Anti-Inflamatórios/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Células RAW 264.7 , Lipopolissacarídeos/efeitos adversos
6.
Inflamm Res ; 71(12): 1547-1557, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36301341

RESUMO

OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) are a major immunosuppressive population in the tumor microenvironment,inhibiting anti-tumor immune response and exerting pro-tumorigenic effect. CCAAT/enhancer-binding protein beta (C/EBPß), a key transcription factor indispensable for myelopoiesis, plays a fundamental role in regulating expansion and activation of MDSCs. Lysine acetylation can regulate functions of transcription factors. However, the role of C/EBPß acetylation modification in MDSCs has not been reported. MATERIALS AND METHODS: MDSCs derived from the spleens of tumor-bearing mice (TB-SP-MDSCs) were isolated by immunomagnetic beads. Bone marrow derived MDSCs were induced by IL-6 and GM-CSF. Western-blot was used to detect the expression of P300 and co-immunoprecipitation (CO-IP) was used to detect the C/EBPß acetylation in MDSCs. Inhibitor C646 was used to specificly inhibit P300 activity. RESULTS: In this study, we found that C/EBPß was acetylated by acetyltransferase P300 in MDSCs. A P300-mediated C/EBPß acetylation enhanced C/EBPß transactivation activity on arginase 1 (Arg-1) gene promoter. Inhibition of P300 activity downregulated the inhibitory effects of MDSCs in vitro and attenuated pro-tumorigenic effects of MDSCs in vivo. Additionally, IL-6 from tumor microenvironment could upregulate the expression of P300 and enhance C/EBPß acetylation in MDSCs. CONCLUSION: In general, a P300-mediated C/EBPß acetylation enhanced C/EBPß transactivation activity on Arg-1 promoter, thus promoting immunosuppressive function of MDSCs. In view of the critical role of P300 in regulating MDSCs, P300 might be a potential target of anti-tumor immunotherapy.


Assuntos
Células Supressoras Mieloides , Neoplasias , Camundongos , Animais , Acetilação , Interleucina-6/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Tolerância Imunológica , Terapia de Imunossupressão , Neoplasias/patologia , Microambiente Tumoral
7.
Soft Matter ; 18(25): 4803-4809, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35713099

RESUMO

The Michael addition 'click' chemistry was used to graft acrylate-terminated mesogenic groups onto the polysiloxane backbone polymer chain with thiol functional groups, with a constant 15% fraction of diacrylate reacting monomers as crosslinkers. Three different types of mesogens were used, and also their 50 : 50 mixtures, and in all cases we have obtained the smectic-A phase of the resulting liquid crystalline elastomer. Using X-ray diffraction, calorimetry and dynamic mechanical analysis, we investigated the relationship between the molecular structure of mesogenic side groups and the structure and properties of the elastomers. The shape-memory of smectic elastomers was verified. The unusual features were the semi-crystalline nature of elastomers with non-polar mesogens and the clear role of side-by-side rod dimerization of polar mesogens leading to a higher smectic layer spacing. We investigated the evolution of the smectic alignment on uniaxial stretching along the layer normal and identified two distinct ways in which the elastomer responds: the coarsened Helfrich-Hurault zig-zag layer texture and the large-scale stripe domains of uniform layer rotation in the systems with lower order parameter and the associated layer constraints.

8.
Planta ; 256(2): 21, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35763091

RESUMO

MAIN CONCLUSION: Based on the phenotypic, physiological and transcriptomic analysis, receptor-like kinase HAESA-like 1 was demonstrated to positively affect seed longevity in Arabidopsis. Seed longevity is very important for both genetic resource conservation and crop production. Receptor-like kinases (RLKs) are widely involved in plant growth, development and stress responses. However, the role of most RLKs, especially in seed longevity, is largely unknown. In this study, we report that Arabidopsis HAESA-like 1 (AtHSL1) positively regulated seed longevity. Disruption of HSL1 significantly decreased the germination rate to 50% at 7 days after cold stratification (DAC), compared with that of the wild type (93.5% at 7 DAC), after accelerated aging treatment. Expression of the HSL1 gene in hsl1 basically restored the defective phenotype (86.3%), while HSL1-overexpressing lines (98.3%) displayed slower accelerated aging than WT (93.5%). GUS staining revealed HSL1 was highly expressed universally, especially in young seedlings, mature seeds and embryos of imbibed seeds, and its expression could be induced by accelerated aging. No difference in the dyeing color and area of mucilage were identified between WT and hsl1. The soluble pectin content also was not different, while the adherent pectin content was significantly increased in hsl1. Global transcriptomics revealed that disruption of HSL1 mainly downregulated genes involved in trehalose synthesis, nucleotide sugar metabolism and protection and repair mechanisms. Therefore, an increase in adherent pectin content and downregulation of genes involved in trehalose synthesis may be the main reasons for decreasing seed longevity owing to disruption of HSL1 in Arabidopsis. Our work provides valuable information for understanding the function and mechanism of a receptor-like kinase, AtHSL1, in seed longevity.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Longevidade , Pectinas/metabolismo , Proteínas Repressoras/genética , Sementes , Trealose
10.
Front Immunol ; 11: 588500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329572

RESUMO

The results of recent studies have shown that granulocytic-myeloid derived suppressor cells (G-MDSCs) can secrete exosomes that transport various biologically active molecules with regulatory effects on immune cells. However, their roles in autoimmune diseases such as rheumatoid arthritis remain to be further elucidated. In the present study, we investigated the influence of exosomes from G-MDSCs on the humoral immune response in murine collagen-induced arthritis (CIA). G-MDSCs exosomes-treated mice showed lower arthritis index values and decreased inflammatory cell infiltration. Treatment with G-MDSCs exosomes promoted splenic B cells to secrete IL-10 both in vivo and in vitro. In addition, a decrease in the proportion of plasma cells and follicular helper T cells was observed in drainage lymph nodes from G-MDSCs exosomes-treated mice. Moreover, lower serum levels of IgG were detected in G-MDSCs exosomes-treated mice, indicating an alteration of the humoral environment. Mechanistic studies showed that exosomal prostaglandin E2 (PGE2) produced by G-MDSCs upregulated the phosphorylation levels of GSK-3ß and CREB, which play a key role in the production of IL-10+ B cells. Taken together, our findings demonstrated that G-MDSC exosomal PGE2 attenuates CIA in mice by promoting the generation of IL-10+ Breg cells.


Assuntos
Artrite Experimental/imunologia , Linfócitos B/imunologia , Dinoprostona/imunologia , Exossomos/imunologia , Células Supressoras Mieloides/imunologia , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/imunologia , Glicogênio Sintase Quinase 3 beta/imunologia , Granulócitos/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA
11.
CrystEngComm ; 22(45): 7847-7857, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33343233

RESUMO

Natural products are precious feedstock in drug discovery and sustainable materials. This work using crystal engineering strategy, visible light, and solvent-free cycloaddition successfully constructed two caffeic acid derivatives, rel-(1R,2R,3S,4S)-2,4-bis(3,4-dihydroxyphenyl)cyclobutane-1,3-dicarboxylate and rel-(1R,2R,3S,4S)-2,4-bis(3,4-dihydroxyphenyl)cyclobutane-1,3-dicarboxylic acid. Because of the multiple stereocenters, it is challenging to prepare those compounds using traditional organic synthesis methods. The crystal engineering Hirshfeld surface analysis and 2D intermolecular interaction fingerprints were applied to synthetic route design. The light resources used in this work was visible LED or free, clean, and renewable sunlight. The evidence suggested that pure stereoisomer was obtained demonstrating the stereospecificity and efficiency of the topochemical cycloaddition reaction. The derivatives exhibited free radical scavenging and antioxidant biological activities, as well as the potential inhibitory activity of fatty acid binding proteins. One of the derivatives is the precursor of the natural product Shimobashiric acid C which paves the way for the total synthesis and further study of Shimobashiric acid C. In addition, the derivatives possess photodegradability at a specific wavelength, which is very attractive for "green" degradable polymeric materials.

12.
Molecules ; 25(18)2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32933060

RESUMO

Rana chensinensis ovum oil (RCOO) is an emerging source of unsaturated fatty acids (UFAs), but it is lacking in green and efficient extraction methods. In this work, using the response surface strategy, we developed a green and efficient CO2 supercritical fluid extraction (CO2-SFE) technology for RCOO. The response surface methodology (RSM), based on the Box-Behnken Design (BBD), was used to investigate the influence of four independent factors (pressure, flow, temperature, and time) on the yield of RCOO in the CO2-SFE process, and UPLC-ESI-Q-TOP-MS and HPLC were used to identify and analyze the principal UFA components of RCOO. According to the BBD response surface model, the optimal CO2-SFE condition of RCOO was pressure 29 MPa, flow 82 L/h, temperature 50 °C, and time 132 min, and the corresponding predicted optimal yield was 13.61%. The actual optimal yield obtained from the model verification was 13.29 ± 0.37%, and the average error with the predicted value was 0.38 ± 0.27%. The six principal UFAs identified in RCOO included eicosapentaenoic acid (EPA), α-linolenic acid (ALA), docosahexaenoic acid (DHA), arachidonic acid (ARA), linoleic acid (LA), and oleic acid (OA), which were important biologically active ingredients in RCOO. Pearson correlation analysis showed that the yield of these UFAs was closely related to the yield of RCOO (the correlation coefficients were greater than 0.9). Therefore, under optimal conditions, the yield of RCOO and principal UFAs always reached the optimal value at the same time. Based on the above results, this work realized the optimization of CO2-SFE green extraction process and the confirmation of principal bioactive ingredients of the extract, which laid a foundation for the green production of RCOO.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Ácidos Graxos Insaturados/análise , Óvulo/química , Animais , Ácido Araquidônico/química , Produtos Biológicos/análise , Dióxido de Carbono , Cromatografia Líquida de Alta Pressão , Ácidos Docosa-Hexaenoicos/química , Ácido Eicosapentaenoico/química , Feminino , Ácido Linoleico/química , Ácido Oleico/química , Valor Preditivo dos Testes , Pressão , Ranidae , Temperatura , Ácido alfa-Linolênico/química
13.
Front Immunol ; 11: 604607, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33414787

RESUMO

Primary Sjögren's syndrome (pSS) is a progressive systemic autoimmune disease characterized by lymphocytic infiltrates in exocrine glands, leading to the injury of salivary and lachrymal glands. Mesenchymal stem cells (MSCs) have been demonstrated to exert great potential in the treatment of various autoimmune diseases. Although MSCs have provide an effective therapeutic approach for SS treatment, the underlying mechanisms are still elusive. Our previous study has shown the reduced suppressive capacity of myeloid-derived suppressor cells (MDSCs) advanced the progression of experimental Sjögren's syndrome (ESS). In this study, we found that BM-MSCs significantly enhanced the suppressive function of MDSCs with high levels of Arginase and NO, decreased the levels of CD40, CD80, CD86, and MHC-II expression on MDSCs, thus attenuating the disease progression in ESS mice. Furthermore, the enhanced suppressive function of MDSCs was mediated by BM-MSC-secreted TGF-ß, and the therapeutic effect of BM-MSCs in inhibiting ESS was almost abolished after silencing TGF-ß in BM-MSCs. Taken together, our results demonstrated that BM-MSCs alleviated the ESS progression by up-regulating the immunosuppressive effect of MDSCs through TGF-ß/Smad pathway, offering a novel mechanism for MSCs in the treatment of pSS.


Assuntos
Comunicação Celular , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Células Supressoras Mieloides/metabolismo , Glândulas Salivares/metabolismo , Síndrome de Sjogren/cirurgia , Animais , Arginase/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Feminino , Masculino , Células-Tronco Mesenquimais/imunologia , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/imunologia , Óxido Nítrico/metabolismo , Fenótipo , Glândulas Salivares/imunologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
14.
Adv Sci (Weinh) ; 6(23): 1802219, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832305

RESUMO

T cells secrete bioactive extracellular vesicles (EVs), but the potential biological effects of CD4+ T cell EVs are not clear. The main purpose of this study is to investigate the effects of CD4+ T cell-derived EVs on B cell responses and examine their role in antigen-mediated humoral immune responses. In this study, CD4+ T cell EVs are purified from activated CD4+ T cells in vitro. After immunization with the Hepatitis B surface antigen (HBsAg) vaccine, CD4+ T cell EVs-treated mice show stronger humoral immune responses, which is indicated by a greater Hepatitis B surface antibody (HBsAb) level in serum and a greater proportion of plasma cells in bone marrow. In addition, it is found that EVs released from activated CD4+ T cells play an important role in B cell responses in vitro, which significantly promote B cell activation, proliferation, and antibody production. Interestingly, antigen-specific CD4+ T cell EVs are found to be more efficient than control EVs in enhancing B cell responses. Furthermore, it is shown that CD40 ligand (CD40L) is involved in CD4+ T cell EVs-mediated B cell responses. Overall, the results have demonstrated that CD4+ T cell EVs enhance B cell responses and serve as a novel immunomodulator to promote antigen-specific humoral immune responses.

15.
Foods ; 8(8)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394825

RESUMO

Oviductus Ranae is a nutritional product for both medicine and food. Its quality is uneven due to multiple factors. An efficient method was established to evaluate the quality of Oviductus Ranae using fingerprint techniques and chemometric methods based on the analysis of polyunsaturated fatty acids (PUFAs) in petroleum ether extract by high performance liquid chromatography (HPLC). During this process, 27 batches of Oviductus Ranae were analyzed by HPLC and two types of chromatographic fingerprints were established. The fingerprint that was obtained by matching six known peaks was used for the quantification of six PUFAs. Another fingerprint was obtained by matching sixteen peaks with a peak area ratio greater than 0.5% and it was used to classify the different qualities of Oviductus Ranae by further combining three different chemometric models. The 27 batches of Oviductus Ranae were divided into four categories, which was consistent with the analysis results of six PUFAs contents. The two high-quality samples with significantly higher contents were classified into one category, and samples with medium contents were divided into two categories, including eight and thirteen samples, respectively. The four inferior samples with lower contents were classified into one category. The results indicated that the newly developed method has potential application prospects for the quality evaluation of Oviductus Ranae.

16.
Biochim Biophys Acta Mol Basis Dis ; 1865(12): 165540, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31470074

RESUMO

The therapeutic effect of myeloid-derived suppressor cells (MDSCs) in mice with collagen-induced arthritis (CIA) remains controversial. We analyzed the role of exosomes derived from granulocytic MDSCs (G-MDSCs) in CIA and explored the potential mechanism underlying the immunosuppressive effect. In CIA mice, G-MDSC-derived exosomes (G-exo) efficiently reduced the mean arthritis index, leukocyte infiltration and joint destruction. G-exo decreased the percentages of Th1 and Th17 cells both in vivo and in vitro. The miR-29a-3p and miR-93-5p contained in G-exo were verified to inhibit Th1 and Th17 cell differentiation by targeting T-bet and STAT3, respectively. Notably, the delivery of exogenous miR-29a-3p and miR-93-5p enhanced the ability of bone marrow-derived G-exo to attenuate arthritis progression in CIA mice. Exosomes derived from human MDSCs, which overexpressed miR-29a-3p and miR-93-5p, suppressed Th1 and Th17 cell differentiation in vitro. These data showed that G-exo alleviated CIA by suppressing Th1 and Th17 cell responses. Mechanistically, miR-29a-3p and miR-93-5p were verified to inhibit the differentiation of Th1 and Th17 cells, respectively. Our findings demonstrated the therapeutic potential of G-MDSC-derived exosomal miRNAs in autoimmune arthritis.


Assuntos
Artrite Experimental/terapia , Exossomos/transplante , Células Supressoras Mieloides/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Bovinos , Células Cultivadas , Colágeno , Exossomos/imunologia , Humanos , Imunidade Celular , Masculino
17.
Molecules ; 24(13)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31247960

RESUMO

Natural products play an important role in drug discovery. This work employed a natural product 1-methylhydantoin as the lead compound to develop novel dual-active drugs. 1-Methylhydantoin was isolated from Oviductus Ranae, which is a traditional Chinese medicine that has been used for tussive and inflammation treatment for a long time. An in silico study screened the more active 1-methylhydantoin derivatives. Antitussive assessment indicated that the newly synthesized agent had similar bioactivity with the natural product. An anti-inflammatory model used xylene induced ear edema model. At the same dosage (100 mg/Kg), the newly prepared agent had an inhibition rate 53.18% which was much higher than that of the lead compound (22.69%). The results might be ascribed to the cyclooxygenases-1 (COX-1) and cyclooxygenases-2 (COX-2) selectivity, and the fitness of the compound, and the binding pocket. The anti-particulate matter (PM 2.5) acute pneumonia was evaluated through an in vivo model constructed by nasal instillation with PM 2.5 suspension. The results of the above models suggested that this novel agent had remarkable antitussive, anti-inflammatory, and anti-PM 2.5 acute pneumonia activities.


Assuntos
Anti-Inflamatórios/farmacologia , Antitussígenos/farmacologia , Produtos Biológicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Hidantoínas/farmacologia , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Antitussígenos/síntese química , Antitussígenos/química , Produtos Biológicos/química , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Desenho de Fármacos , Medicamentos de Ervas Chinesas/síntese química , Medicamentos de Ervas Chinesas/química , Hidantoínas/síntese química , Hidantoínas/química , Camundongos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade
18.
Molecules ; 24(9)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052194

RESUMO

This work demonstrated a method combining reversed-phase high-performance liquid chromatography (RP-HPLC) with chemometrics analysis to identify the authenticity of Ranae Oviductus. The fingerprint chromatograms of the Ranae Oviductus protein were established through an Agilent Zorbax 300SB-C8 column and diode array detection at 215 nm, using 0.085% TFA (v/v) in acetonitrile (A) and 0.1% TFA in ultrapure water (B) as mobile phase. The similarity was in the range of 0.779-0.980. The fingerprint chromatogram of Ranae Oviductus showed a significant difference with counterfeit products. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) successfully identified Ranae Oviductus from the samples. These results indicated that the method established in this work was reliable.


Assuntos
Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Materia Medica/química , Mapeamento de Peptídeos , Proteínas de Plantas/química , Análise por Conglomerados , Materia Medica/classificação , Mapeamento de Peptídeos/métodos , Proteínas de Plantas/análise , Proteínas de Plantas/isolamento & purificação , Reprodutibilidade dos Testes
19.
J Immunol ; 202(6): 1693-1703, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30760623

RESUMO

Although the expansion of myeloid-derived suppressor cells (MDSCs) has been reported in autoimmune disorders, it is largely unclear how MDSCs contribute to the development of primary Sjögren syndrome (pSS). In this study, we found significantly increased MDSCs with gradually diminished suppressive capacity during disease development in mice with experimental Sjögren syndrome (ESS). The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased along ESS progression, whereas the increased GITRL was found to attenuate the immunosuppressive function of MDSCs. Moreover, blocking GITR signal in MDSCs significantly restored their immunosuppressive function and alleviated ESS progression in mice. In pSS patients, expanded MDSCs were found to express low levels of arginase. Significantly increased serum GITRL levels were closely correlated with patients with higher Sjögren syndrome disease activity index. Furthermore, treatment with recombinant GITRL markedly reduced the immunosuppressive function of human MDSCs. Together, our studies have demonstrated a critical role of GITRL in modulating the suppressive function of MDSCs, which may facilitate the validation of GITRL as a therapeutic target for the treatment of pSS.


Assuntos
Células Supressoras Mieloides/imunologia , Síndrome de Sjogren/imunologia , Fatores de Necrose Tumoral/imunologia , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Células Supressoras Mieloides/metabolismo , Síndrome de Sjogren/metabolismo , Fatores de Necrose Tumoral/metabolismo
20.
RSC Adv ; 9(62): 36050-36057, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-35540582

RESUMO

This work studied the influences of environmental factors on the quality features of Oviductus Ranae. Oviductus Ranae is mainly produced in the Changbai Mountains. The samples of Oviductus Ranae were collected from 24 different locations, which covered the main producing areas. The environmental parameters were assessed using a digital raingauge, GPS, a thermometer, and an atmospheric pressure-altimeter. The quality features including expansion degree, ethanol extract, total water, total ash, and five steroid components, of the collected Oviductus Ranae samples were quantified using high-performance liquid chromatography. The results showed that the cholesterol content in the samples collected from the Yanbian Korean region was slightly higher than the others. Samples collected from the Huadian area exhibited much higher contents of 7-hydroxycholesterol and 7-dehydrocholesterol than the rest of the producing areas. The highest content of cholest-4-en-3-one came from the samples collected from Dandong. The contents of 7-keto-cholesterol in samples from different regions were very close. The highest ethanol extract was from the samples in Tonghua. The correlations between the quality features and environmental factors were analyzed by SPSS (version 25.0, SPSS Inc., Chicago, IL, USA). The results showed that the content of cholest-4-en-3-one was related to the annual average temperature. The total water was correlated with the annual precipitation. 7-Hydroxycholesterol and expansion degree were related to the altitude. The results indicated that environmental factors have certain influences on the quality features.

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