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1.
J Am Soc Mass Spectrom ; 31(4): 856-863, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32125841

RESUMO

Mast cells are essential in mediating inflammatory processes. When activated, mast cells can rapidly release characteristic granules and various mediators into the interstitium. Tryptase (TPS) and ß-hexosaminidase (HEXB) are typical protease mediators stored in granules and released upon activation. They have been recognized as important biomarkers of anaphylaxis, and the released level is associated with the severity of allergic reactions. In this study, a sensitive, accurate, and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneously quantifying the two biomarkers was developed and validated in LAD2 cell culture supernatant, and P14R was used as internal standard. Good linearity was observed in the range of 50-2500 ng/mL for TPS and 10-2000 ng/mL for HEXB both with R2 > 0.99. The matrix effect and recovery were both within acceptable limits. We quantified TPS and HEXB released from Laboratory of Allergic Disease 2 (LAD2) mast cells treated with several potential allergens, and the results demonstrate that the method can be used to investigate TPS and HEXB levels in LAD2 mast cell model during allergy research. We anticipate our approach to be a robust and sensitive assessment method for more biomarkers with similar kinetics characteristics and to be a major tool of allergic drug assessment or antiallergic drug development in research.

2.
Vaccine ; 38(14): 2978-2983, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32113807

RESUMO

Botulinum neurotoxins (BoNTs) are highly toxic proteins that mediate their effects by binding to neuronal receptors and block the neutralizing ability of therapeutic antibodies. Vaccination is currently the most effective strategy to prevent botulism. In this study, a series of recombinant functional domain antigens of BoNT/A were prepared and identified, and their immunoprotective efficacies were explored and compared. Our results showed that all antigens produced strong humoral immune responses, although their protective effects against the toxin were different. Only the Hc and HN-L antigens produced strong protective effects and afforded complete immunoprotection. In addition, the combined vaccine groups showed that there was no synergistic effect on immune responses after antigen combination, suggesting that the integrity of the toxin antigen or domain is crucial to the immune effects. Studies of the dose-dependent immunoprotective effects further confirmed that the Hc domain antigen afforded more effective protective potency than the HN-L antigen, equivalent to the immune effect of the full-length toxin (Hc + HN-L combination group). Overall, our results demonstrated that the Hc domain elicited a strong protective immune response and also provided basic data and theoretical support for the development of Hc-based BoNT/A subunit vaccine. Therefore, the receptor binding domain Hc is implicated as a promising target antigen of the BoNT/A recombinant subunit vaccine as an alternative to the toxoid vaccine.

3.
Nanotechnology ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191937

RESUMO

Transition metal oxides have recently been demonstrated as highly attractive anodes for high-capacity lithium ion batteries, whose electrochemical properties could be further improved through rational architecture design and incorporating reliable conductive network. Herein, mesoporous γ-Fe2O3 spheres/graphene aerogel composites were synthesized via a solvothermal pathway followed by suitable annealing. Experimental results reveal the uniform mesoporous structure and well-dispersed γ-Fe2O3 spheres with the size of 300-400 nm embedded in the mesopores of the graphene aerogel network. Compared with α-Fe2O3/graphene aerogel and pure γ-Fe2O3, the as-synthesized composite delivers, at the first cycle, a high discharging capacity of 1080 mAh g-1 at current density of 200 mA g-1. Even at much higher current density of 8000 mA g-1, satisfactory discharging capacities of 421.5 mAh g-1 can still be achieved. Upon 100 charging-discharging cycles, the specific capacity of as high as 890.5 mAh g-1 at 200 mA g-1 is maintained. The enhanced electrochemical properties could be attributed to their favorable three-dimensional graphene aerogel network, which accounts for the improved structural stability and electronic conductivity of γ-Fe2O3 during the lithiation/delithiation process.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32099346

RESUMO

Purpose: To evaluate the associations between acute exacerbations of chronic obstructive pulmonary disease (AECOPD) hospitalizations and daily mean temperature (Tmean) as well as daily apparent temperature (AT), and to explore the practical values of these two indices in policymaking and patient education. Methods: Daily AECOPD hospitalizations and Meteorological data in Beijing were obtained between 2013 and 2016. Distributed lag non-linear model was adopted to investigate the association between daily ambient temperature and AECOPD hospitalizations. The cumulative effects of cold/hot temperature were abstracted. For the extreme and moderate low-temperature effect estimates, we, respectively, computed the RR of AECOPD hospitalizations at the 1st and 10th percentiles of temperature in comparison with that at the 25th percentile of temperature. For the extreme and moderate high temperature effect estimates, we, respectively, computed the RR of AECOPD hospitalizations at the 99th and 90th percentiles of temperature in comparison with that at the 75th percentile of temperature. Results: During the study period, 143, 318 AECOPD hospitalizations were collected. A reverse J-shape relationship was found between temperature and AECOPD hospitalizations. When comparing the effect of Tmean, higher RRs were associated with increases in AT on AECOPD hospitalizations but a lower value of Akaike's Information Criterion for quasi-Poisson (Q-AIC). The RR of extremely low temperature of Tmean and AT were 1.55 (95% CI: 1.21,2.00) and 2.08 (95% CI: 1.44,3.01), respectively. Moderate low temperature also had an adverse impact on AECOPD hospitalizations. No associations were found between high temperature and AECOPD risk. We found the females and those aged <65 years to be more susceptible to temperature change. Conclusion: Lower temperature is associated with a higher risk for AECOPD hospitalizations. Ambient temperature is probably a better predictor in terms of quantifying risk than mean temperature when studying temperature impact on health.

5.
Eur J Radiol ; 125: 108825, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32035324

RESUMO

PURPOSE: To determine if texture features of diffusion weighted imaging (DWI) on MRI of metastatic gastrointestinal stromal tumor (mGIST) have correlation with overall survival (OS). METHOD: Fifty-one GIST patients with metastatic lesions who received imatinib targeted therapy were included. Texture features of the largest metastatic lesion were analyzed using inhouse software. Three types of texture features were assessed: fractal features, gray-level co-occurrence matrix (GLCM) features, and gray-level run-length matrix (GLRLM) features. The features were extracted from the regions of interest (ROIs) on T2-weighted imaging (T2WI), DWI and apparent diffusion coefficient (ADC) maps. Histogram analysis was performed on ADC maps. Patients were followed up until death. Kaplan-Meier analysis was performed to determine the correlation of texture features with OS. The curves of the high- and low-risk groups were compared using log-rank test. The prognostic efficacy of the predictors was assessed by calculating the concordance probability. RESULTS: The median survival time was 43.5 months (range, 3.97-120.90 m). Four DWI and three ADC texture features showed significant correlation with OS on univariate analysis (p < 0.05). DWI_L_GLCM_maximum_probability [hazard ratio (HR): 2.062 (1.357-3.131)], ADC_H_GLRLM_mean [HR: 2.174 (1.457-3.244)], and ADC_O_GLCM_cluster_shade [HR: 1.882 (1.324-2.674)] were identified as representative prognostic indicators. The optimum threshold levels for these three features were 1.19×100, 1.71×10 and 2.19×0.1, respectively. Neither histogram analysis values nor fractal features revealed significant correlation with survival status (p > 0.05). CONCLUSIONS: Texture features of the mGIST on DWI exhibited correlation with overall survival. High-grade heterogeneity was associated with poor prognosis.

6.
Medicine (Baltimore) ; 99(7): e19138, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049835

RESUMO

The study assessed the pelvic dimensions by computed tomography (CT) performed for gluteal muscle contracture women, and evaluated the impact of malformations on several essential obstetric parameters.The CT pelvimetry was retrospectively performed in 25 gluteal muscle contracture women selected consecutively whether they had delivery history or not. Among the pelvic inlet plane, the mid plane and the outlet plane, 12 indicators including the transverse diameter of the pelvic inlet, the conjugate vera, the diagonal conjugate, the biischial diameter, the anteroposterior diameter of the middle pelvis, transverse outlet, the posterior sagittal diameter of outlet, the conjugate of the outlet, the anterior sagittal diameter of the outlet, the curvature and length of the sacrum, the angle of pubic arch were collected.Finally, the mean age of these women was 26.6 ±â€Š5.0 years. Most pelvises had anteroposterior elliptical appearance in inlet and size of the female pelvis. The most statistically different and most clinically significant indicator was the biischial diameter, gluteal muscle contracture women were 95.6 ±â€Š9.3 mm and the normal women from other study were 105.0 ±â€Š7.9 mm, the comparison showed a significant difference (P < .001).Generally, most gluteal muscle contracture women had features of anthropoid pelvis which were quite different from normal Chinese female. These results may serve as a basis for future studies to assess its utility and prognostic value for a safe vaginal delivery in gluteal muscle contracture women.


Assuntos
Nádegas/diagnóstico por imagem , Distocia/etiologia , Músculo Esquelético/diagnóstico por imagem , Ossos Pélvicos/diagnóstico por imagem , Adolescente , Adulto , Nádegas/patologia , Nádegas/fisiopatologia , Feminino , Fibrose , Humanos , Músculo Esquelético/fisiopatologia , Ossos Pélvicos/patologia , Gravidez , Síndrome , Adulto Jovem
7.
Adv Mater ; : e1907307, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32048339

RESUMO

High temperature brings adverse impacts on the energy efficiency, and even destroys a semiconductor device. Here, a novel and cost-effective strategy is proposed to boost the energy efficiency of semiconductor devices by using the self-adaptive evaporative cooling of a lithium- and bromine-enriched polyacrylamide hydrogel. Water inside the hydrogel can quickly evaporate to dissipate the waste heat generated by the nugatory carrier transport in the P-N junction. In dormancy, the hydrogel harvests water molecules from the surrounding air to regenerate itself. The hydrogel is demonstrated to low down the operating temperature of a commercial polycrystalline silicon solar cell by 17 °C under one sun condition and enhances its efficiency from 14.5% to 15.5%. It is also capable of increasing the maximum power of a simulated chip by 45% at a fixed operating temperature. The hydrogel is expected to be widely adopted in current semiconductor industry to improve its energy efficiency.

8.
Molecules ; 25(4)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32092902

RESUMO

The impairment in diabetic wound healing represents a significant clinical problem, with no efficient targeted treatments for these wound disorders. Curcumin is well confirmed to improve diabetic wound healing, however, its low bioavailability and poor solubility severely limit its clinical application. This study aims to provide the pharmacological basis for the use of (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66). The results showed that topically applied C66 improved cutaneous wound healing in vivo. Further studies showed that C66 treatment increased the level of microRNA-146a (miR-146a) in the wounds in streptozotocin (STZ)-induced diabetic mice, downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) and phosphorylated nuclear factor-κB (NF-κB) p65 subunit (p-p65) (both p < 0.05), and suppressed the mRNA expression of inflammation-related cytokines, tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6). The in vitro data obtained in human umbilical vein endothelial cells (HUVECs) showed that C66 could reverse high glucose (HG)-induced NF-κB activation due to upregulation of miR-146a expression, which matched the in vivo findings. In conclusion, the present study indicates that C66 exerts anti-inflammation activity and accelerates skin wound healing of diabetic mice, probably via increasing miR-146a and inhibiting the NF-κB-mediated inflammation pathway. Therefore, C66 may be a promising alternative for the treatment of diabetic wounds.

9.
J Orthop Surg (Hong Kong) ; 28(1): 2309499019900274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31994976

RESUMO

INTRODUCTION: The efficacy of intra-articular fentanyl supplementation for pain control after knee arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of intra-articular fentanyl supplementation for pain intensity after arthroscopic knee surgery. METHODS: We searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through May 2019 for randomized controlled trials (RCTs) assessing the efficacy and safety of intra-articular fentanyl supplementation for arthroscopic knee surgery. This meta-analysis is performed using the random-effects model. RESULTS: Four RCTs are included in the meta-analysis. Overall, compared with control group after knee arthroscopy, intra-articular fentanyl supplementation is associated with reduced pain scores at 1 h (standard mean difference (Std MD) = -3.50; 95% confidence interval (CI) = -5.68 to -1.32; p = 0.002), 2 h (Std MD = -4.73; 95% CI = -8.75 to -0.71; p = 0.02), and 8 h (Std MD = -5.02; 95% CI = -9.73 to -0.30; p = 0.04) but shows no substantial impact on pain scores at 4 h (Std MD = -3.94; 95% CI = -7.93 to 0.05; p = 0.05) or the supplementary analgesia (risk ratio = 0.56; 95% CI = 0.09-3.59; p = 0.54). CONCLUSIONS: Intra-articular fentanyl supplementation does benefit in pain control after knee arthroscopy.

10.
Biomed Pharmacother ; 124: 109887, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31986414

RESUMO

PURPOSE: Long non-coding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) and Yin Yang 1 (YY1) are reported to be involved in tumorigenesis. However, the effect and molecular mechanism of HOTAIR on YY1 expression remains poorly understood. The study aimed to investigate the functions and molecular mechanism of LncRNA HOTAIR in medulloblastoma progression. METHODS: qPCR was performed to detect HOTAIR and YY1 mRNA in tissues and cells, as well as that of miR-1 and miR-206 expression levels. Western blot assay was used to test YY1 and EMT-related biomarkers' protein levels. Cell proliferation was tested with CCK-8 assay and colony formation assay. Migration and invasion abilities were tested with Transwell migration and invasion assays. Tumor growth was tested with an in vivo animal study. Cell apoptosis was tested with an Annexin V-FITC/PI kit. Luciferase assay was used to test the luciferase intensity of YY1 and HOTAIR. RNA pull down assay was used to detect the combination between HOTAIR and miR-1/miR-206. RESULTS: In this study, we found that HOTAIR and YY1 were up-regulated in medulloblastoma tissues and cell lines, and HOTAIR increased YY1 expression. The molecular mechanism demonstrated that HOTAIR negatively regulated miR-1 and miR-206 expression, which can directly target YY1 in medulloblastoma cells. Moreover, HOTAIR increased YY1 expression through binding to miR-1 and miR-206. The functional experiments showed that HOTAIR knockdown suppressed medulloblastoma cell proliferation, tumor growth, migration and invasion, and promoted cell apoptosis via the modulation of the miR-1/miR-206-YY1 axis, as well as epithelial to mesenchymal transition (EMT). CONCLUSION: These data indicate that HOTAIR promotes medulloblastoma progression via acting as a competing endogenous RNA (ceRNA) to regulate YY1 expression through binding to miR-1 and miR-206.

11.
Talanta ; 209: 120539, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892067

RESUMO

Anaphylactoid reactions induced by drugs are serious and can be life-threatening, and screening the anaphylactoid ingredients especially in complex samples is challenging. Here, a multi targeted cell membrane chromatography method, based on the Mas-related G protein coupled receptor X2, Fc epsilon RI and H1 receptors, online coupled with LC-MS system provides a comprehensive solution for screening the anaphylactoid components from complex samples. The validation including selectivity and suitability of this system has been evaluated, and it shows promising results. With optimized conditions, this method has been utilized to screen the anaphylactoid ingredients from Shenmai Injection. Ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rc, ginsenoside Rd and 20(S)-ginsenoside Rg3 were identified as anaphylactoid components. The anaphylactoid effects of these five components were further verified by the in vitro sensitization assay, showing promising effects on some or all sensitization cells. In conclusion, the multi targeted cell membrane chromatography online coupled with LC-MS system developed throughout this study could be used to fully screen anaphylactoid components in complex samples. Moreover, it also provides new insights for drug quality control.

12.
BMC Cancer ; 20(1): 35, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941467

RESUMO

BACKGROUND: The prognosis of glioma is poor, despite recent advances in diagnosis and treatment of the disease. It is important to investigate the clinical characteristics and prognostic factors of glioma so as to provide basis for treatment and management of patients. METHOD: A total of 335 patients with glioma were included in this study. These patients were admitted to the medical center between November 2015 and December 2018. The clinical data, including demographic data, tumor characteristics, treatment strategy, expression pattern of tumor markers, and survival data, were retrospectively reviewed. Survival data were analyzed using Kaplan-Meier curves with log-rank test, while multivariate analysis Cox regression model was used to investigate risk factors for mortality. RESULTS: In this patient cohort, glioblastoma (40%), diffuse glioma (14.6%) and oligodendroglioma (9.6%) were the most common pathological types. The expression of Ki-67 was associated with several clinicopathological parameters (e.g. tumor type, grade, and number of lesions). In addition, Ki-67 correlated with the mortality within the first year of the post-treatment follow-up (P <  0.001). Kaplan-Maier analysis revealed that older patients (≥ 45 years) displayed worse prognosis than those aged under 45 years (P = 0.038). Dismal prognosis was also associated with clinical parameters, including high tumor grade, multiple lesions, and Karnofsky performance score (KPS). Multivariate analysis showed that low KPS (< 85) increased the risk of mortality by 2.3 folds with a 95% CI of 1.141 to 4.776 (P = 0.020). Low tumor grade (grade 1-2) oppositely reduced the mortality risk by 0.22 folds (95% CI, 0.065 to 0.763, P = 0.0168). CONCLUSION: KPS and tumor grade were independent prognostic factors in patients with gliomas.

13.
Cancer Biol Ther ; 21(4): 372-378, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-31910710

RESUMO

Background: Associations between polymorphisms in interleukin-10 (IL-10) and hematological oncology were already explored by many genetic association studies, with controversial findings. The aim of this meta-analysis was to more comprehensively analyze associations between polymorphisms in IL-10 and hematological oncology by combing the results of all relevant studies.Methods: Eligible articles were searched from Pubmed, Embase, WOS and CNKI. The latest literature searching update was performed on 8 October 2019. We used Review Manager to combine the results of eligible studies.Results: Forty-one articles were included in this meta-analysis. IL-10 rs1800890 polymorphism was found to be significantly associated with hematological oncology under AA vs. TT+TA (recessive comparison, OR = 1.12, 95% CI 1.02-1.24), and rs1800896 polymorphism was also found to be significantly associated with hematological oncology under AA vs. AG+GG (dominant comparison, OR = 0.89, 95% CI 0.83-0.95) in overall combined analyses. In subgroup analyses, we observed positive results for rs1800871 (recessive comparison), rs1800872 (dominant, recessive and allele comparisons), and rs1800896 (dominant and allele comparisons) polymorphisms in the non-Hodgkin's lymphoma (NHL) subgroup. Besides, we also detected positive associations between rs1800872 polymorphism and acute leukemia (AL) (dominant and recessive comparisons) and found significant associations between rs1800896 polymorphism and chronic leukemia (CL) (recessive comparison).Conclusion: In summary, this meta-analysis demonstrated that IL-10 rs1800890, rs1800896, rs1800871 and rs1800872 polymorphisms may confer susceptibility to hematology oncology, especially for NHL.

14.
Ann Surg Oncol ; 27(4): 1103-1109, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31965376

RESUMO

BACKGROUND: Preoperative diagnosis of peritoneal metastasis with gastric cancer remains challenging. This study explored the abnormal computed tomography (CT) signs of occult peritoneal metastasis (OPM) and evaluated it by region-to-region comparison using staging laparoscopy, from which a 4-point CT score system was developed. METHODS: Patients with advanced gastric cancer (stage cT ≥ 2M0) diagnosed by CT were enrolled in the study. Occult peritoneal metastasis detected during staging laparoscopy was compared with preoperative CT to investigate the presence of abnormal signs by a region-to-region comparison. A 4-point CT score system was developed to define the radiologic characteristics. Subsequently, the diagnostic efficacy of the CT score system was prospectively verified. RESULTS: In this study, 57 OPM regions were detected by staging laparoscopy in 33 of the 385 enrolled patients. The greater omentum was the most frequent site of OPM (38.60%, 22/57), which usually exhibited a smudge-like ground-glass opacity (S-GGO) (90.91%, 20/22) with a mean CT score of 2.14. The parietal and perihepatic peritoneum was the second most common site (22.81%, 13/57). A 4-point CT score system was developed based on the results. A cutoff CT score of 2 or higher was associated with a false-negative rate of 2% (2/99). This CT score system had a sensitivity of 87.5% and a specificity of 76.4% for an OPM-positive diagnosis (area under the curve, 0.848). The agreement between two radiologists on the assigned final score was 76.2% (kappa, 0.5). CONCLUSIONS: Patients with OPM mostly exhibited S-GGO on CT, which should be interpreted cautiously. The 4-point CT score system may improve the pretreatment evaluation of occult peritoneal metastasis, and staging laparoscopy might not be necessary for patients with a score lower than 2.

15.
Fitoterapia ; 140: 104417, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707125

RESUMO

Schefflera rubriflora, a plant native to Yunnan Province in China, is often used to treat ailments such as neuropathic pain, tracheitis, and cough. However, the active components imparting these pharmacological effects are largely unexplored. In this study, five novel lignans and three new derivatives of benzoid or pyran were isolated from the leaves and twigs of S. rubriflora. The structures of these compounds were determined by the comprehensive analyses of the 1D and 2D NMR spectra and ESI mass spectra and a comparison of the obtained data with those of the literature data. All the compounds were tested for the inhibition of IL-6 expression. Three of the isolated compounds could inhibit the expression by 52% to 72%.


Assuntos
Araliaceae/química , Interleucina-6/antagonistas & inibidores , Lignanas/farmacologia , Animais , China , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Células RAW 264.7
16.
J Surg Res ; 246: 213-223, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31606511

RESUMO

BACKGROUND: For patients with diabetes mellitus, excessive and long-lasting inflammatory reactions at the wound site commonly lead to the delayed refractory wound healing. The polarization of macrophages in terms of M1 and M2 phenotypes is closely related to the production of inflammatory cytokines. Quercetin is traditionally recognized to have anti-inflammatory effect; however, whether quercetin modulates macrophage polarization from M1 to M2 and thus promotes diabetic wound healing remain unknown. MATERIALS AND METHODS: Wounded male diabetic rats were equally divided into five groups: model group, solvent control group (10% DMSO), and three drug groups treated with quercetin (Q) at concentrations of 10 mg/mL (Q-LD [low dose]), 20 mg/mL (Q-MD [medium dose]), and 40 mg/mL (Q-HD [high dose]), respectively. The anti-inflammatory effect of quercetin on diabetic wounds was observed. Immunohistochemistry and quantificational real-time polymerase chain reaction were applied to test the changes in macrophage polarization and inflammatory responses. RESULTS: The wound contraction was fastest in Q-HD group. Hematoxylin and eosin (H&E) and Masson's trichrome staining revealed that fibroblast distribution and collagen deposition in quercetin-treated groups were significantly higher than those in the model group. Immunohistochemistry tests showed more CD206-positive cells and less iNOS-positive cells in quercetin-treated groups. Furthermore, the levels of proinflammatory factors in quercetin-treated groups were lower than those in the model group, whereas the levels of the anti-inflammatory factors and angiogenesis-related factors were relatively higher. CONCLUSIONS: In short, quercetin inhibits inflammatory reactions via modulating macrophage polarization switching from M1 to M2 phenotype, thereby accelerating the diabetic wound repair.


Assuntos
Diabetes Mellitus Experimental/complicações , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Quercetina/administração & dosagem , Pele/lesões , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/imunologia , Relação Dose-Resposta a Droga , Humanos , Inflamação/imunologia , Inflamação/patologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Ratos , Pele/imunologia , Pele/patologia , Estreptozocina/toxicidade , Resultado do Tratamento , Cicatrização/imunologia
17.
Hum Vaccin Immunother ; 16(1): 100-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31210561

RESUMO

Botulinum neurotoxins (BoNTs) are among the most toxic proteins. Vaccination is an effective strategy to prevent botulism. To generate a vaccine suitable for human use, a recombinant non-His-tagged isoform of the Hc domain of botulinum neurotoxin serotype E (rEHc) was expressed in Escherichia coli and purified by sequential chromatography. The immunogenicity of rEHc was evaluated in mice and dose- and time-dependent immune responses were observed in both antibody titers and protective potency. Then, the pilot-scale expression and purification of rEHc were performed, and its immunological activity was characterized. Our results showed rEHc has good immunogenicity and can elicit strong protective potency against botulinum neurotoxin serotype E (BoNT/E) in mice, indicating that rEHc is an effective botulism vaccine candidate. Further, we developed a novel antitoxin against BoNT/E by purifying F(ab')2 from pepsin-digested serum IgG of rEHc-inoculated horses. The protective effect of the F(ab')2 antitoxin was determined in vitro and in vivo. The results showed that our F(ab')2 antitoxin can prevent botulism in BoNT/E-challenged mice and effectively alleviate the progression of paralysis caused by BoNT/E to achieve therapeutic effects. Therefore, our results provide valuable experimental data for the production of a novel antitoxin, which is a promising candidate for the treatment of BoNT/E-induced botulism.

18.
Zool Res ; 41(1): 90-93, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31746566

RESUMO

The development of an effective tetravalent vaccine against dengue viruses (DENVs) has become a world priority. We previously showed that four monovalent dengue DNA vaccines expressing premembrane (prM) and envelope (E) proteins displayed effective protection against corresponding challenges in mice. Thus, to elucidate the overall immunity and persistence of the tetravalent formulation (TetraME), we evaluated the humoral and cellular immune responses as well as the long-term protection in the current study. TetraME-immunized mice displayed increased production of Th1/Th2-typed cytokines upon stimulation with heterologous DENV antigens. Moreover, high levels of tetravalent DENV antibodies and sterilized immunity were detected long-term (30 weeks after immunization). These findings provide feasible validation for the potential utility of this vaccine formulation.


Assuntos
Vacinas contra Dengue/imunologia , Dengue/prevenção & controle , Animais , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Citocinas/genética , Citocinas/metabolismo , Camundongos , Vacinas de DNA/imunologia
19.
Mol Nutr Food Res ; 64(2): e1900905, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31837280

RESUMO

SCOPE: To evaluate the health-promoting potentials of piceatannol (PIC), a dietary resveratrol derivative, its biotransformation is examined. METHODS AND RESULTS: The biotransformation is tested in human/rat hepatic microsomes and cytosols; its pharmacokinetic profiles are assessed in rats. Although limited phase I metabolism exists in microsomes, PIC is rapidly converted to two pharmacologically active metabolites, namely rhapontigenin (RHA) and isorhapontigenin (ISO) in cytosols. Such biotransformation is completely blocked by entacapone, a well-known catechol-O-methyltransferase (COMT) inhibitor, demonstrating that the O-methylation is mediated by COMT. Moreover, PIC is identified as a substrate inhibitor of COMT, suggesting its potential benefits in Alzheimer's disease. Due to extensive phase II metabolism including glucuronidation, sulfation, and O-methylation, PIC displays rapid clearance and at least 4.02% ± 0.61% and 17.70% ± 0.91% of PIC is converted to RHA and ISO, respectively, in rats after intravenous administration. Similarly, PIC serves as an effective precursor of ISO upon oral administration. CONCLUSION: Since PIC and its metabolites possess pleiotropic health-promoting activities, it has emerged as a promising nutraceutical candidate for further development. This study also reinforces the importance of in vivo testing in nutritional researches as the active metabolite(s) may be absent from the in vitro system.

20.
Nat Cell Biol ; 21(12): 1553-1564, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31768048

RESUMO

Redox balance, an essential feature of healthy physiological steady states, is regulated by circadian clocks, but whether or how endogenous redox signalling conversely regulates clockworks in mammals remains unknown. Here, we report circadian rhythms in the levels of endogenous H2O2 in mammalian cells and mouse livers. Using an unbiased method to screen for H2O2-sensitive transcription factors, we discovered that rhythmic redox control of CLOCK directly by endogenous H2O2 oscillations is required for proper intracellular clock function. Importantly, perturbations in the rhythm of H2O2 levels induced by the loss of p66Shc, which oscillates rhythmically in the liver and suprachiasmatic nucleus (SCN) of mice, disturb the rhythmic redox control of CLOCK function, reprogram hepatic transcriptome oscillations, lengthen the circadian period in mice and modulate light-induced clock resetting. Our findings suggest that redox signalling rhythms are intrinsically coupled to the circadian system through reversible oxidative modification of CLOCK and constitute essential mechanistic timekeeping components in mammals.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Peróxido de Hidrogênio/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Animais , Feminino , Fígado/metabolismo , Fígado/fisiologia , Masculino , Mamíferos/metabolismo , Mamíferos/fisiologia , Camundongos , Camundongos Knockout , Oxirredução , Proteínas Circadianas Period/metabolismo , Transdução de Sinais/fisiologia , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/fisiologia
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