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BACKGROUND: Mast cells (MCs) are important effector cells in anaphylaxis and anaphylactic disease. 3',4',5,7-tetrahydroxyflavone (THF) presents in many medicinal plants and exerts a variety of pharmacological effects. In this study, we evaluated the effect of THF on C48/80-induced anaphylaxis and the mechanisms underlying its effects, including the role of secreted phosphoprotein 1 (SPP1), which has not been reported to IgE-independent MC activation. RESULTS: THF inhibited C48/80-induced Ca2+ flow and degranulation via the PLCγ/PKC/IP3 pathway in vitro. RNA-seq showed that THF inhibited the expression of SPP1 and downstream molecules. SPP1 is involved in pseudo-anaphylaxis reactions. Silencing SPP1 affects the phosphorylation of AKT and P38. THF suppressed C48/80-induced paw edema, hypothermia and serum histamine, and chemokines release in vivo. CONCLUSIONS: Our results validated SPP1 is involved in IgE-independent MC activation anaphylactoid reactions. THF inhibited C48/80-mediated anaphylactoid reactions both in vivo and in vitro, suppressed calcium mobilization and inhibited SPP1-related pathways.
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Anafilaxia , Humanos , Anafilaxia/inducido químicamente , Anafilaxia/tratamiento farmacológico , Luteolina/farmacología , Osteopontina/metabolismo , Osteopontina/farmacología , Mastocitos , Inflamación/metabolismo , Degranulación de la Célula , Inmunoglobulina E/metabolismoRESUMEN
Patients have different responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and these may be life-threatening for critically ill patients. Screening components that act on host cell receptors, especially multi-receptor components, is challenging. The in-line combination of dual-targeted cell membrane chromatography and a liquid chromatography-mass spectroscopy (LC-MS) system for analyzing angiotensin-converting enzyme 2 (ACE2) and cluster of differentiation 147 (CD147) receptors based on SNAP-tag technology provides a comprehensive solution for screening multiple components in complex samples acting on the two receptors. The selectivity and applicability of the system were validated with encouraging results. Under the optimized conditions, this method was used to screen for antiviral components in Citrus aurantium extracts. The results showed that 25 µmol /L of the active ingredient could inhibit virus entry into cells. Hesperidin, neohesperidin, nobiletin, and tangeretin were identified as antiviral components. In vitro pseudovirus assays and macromolecular cell membrane chromatography further verified the interaction of these four components with host-virus receptors, showing good effects on some or all of the pseudoviruses and host receptors. In conclusion, the in-line dual-targeted cell membrane chromatography LC-MS system developed in this study can be used for the comprehensive screening of antiviral components in complex samples. It also provides new insight into small-molecule drug-receptor and macromolecular-protein-receptor interactions.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Enzima Convertidora de Angiotensina 2 , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Membrana Celular/metabolismo , Antivirales/farmacologíaRESUMEN
Asthma is a heterogeneous disease related to numerous inflammatory cells, among which mast cells play an important role in the early stages of asthma. Therefore, treatment of asthma targeting mast cells is of great research value. α-Asarone is an important anti-inflammatory component of the traditional Chinese medicine Acorus calamus L, which has a variety of medicinal values. To investigate whether α-asarone can alleviate asthma symptoms and its mechanism. In this study, we investigated the effect of α-asarone on mast cell activation in vivo and in vitro. The release of chemokines or cytokines, AHR (airway hyperresponsiveness), and mast cell activation were examined in a mast cell-dependent asthma model. Western blot was performed to determine the underlying pathway. α-Asarone inhibited the degranulation of LAD2 (laboratory allergic disease 2) cells and decreased IL-8, MCP-1, histamine, and TNF-α in vitro. α-Asarone reduced paw swelling and leakage of Evans blue, as well as serum histamine, CCL2, and TNF-α in vivo. In the asthma model, α-asarone showed an inhibitory effect on AHR, inflammation, mast cells activation, infiltration of inflammatory cells, and the release of IL-5 and IL-13 in lung tissue. α-Asarone decreased the levels of phosphorylated JAK2, phosphorylated ERK, and phosphorylated STAT3 induced by C48/80. Our findings suggest that α-asarone alleviates allergic asthma by inhibiting mast cell activation through the ERK/JAK2-STAT3 pathway.
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Asma , Mastocitos , Humanos , Asma/inducido químicamente , Asma/metabolismo , Citocinas/metabolismo , Histamina/metabolismo , Histamina/farmacología , Janus Quinasa 2/efectos adversos , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Sistema de Señalización de MAP QuinasasRESUMEN
Protein corona (PC) adsorbed on the surface of nanoparticles brings new research perspectives on the interaction between nanoparticles and fermentative microorganisms. Herein, the proteolysis of wheat PC adsorbed on a nano-Se surface using cell-free protease extract from S. cerevisiae was conducted. The proteolysis caused monotonic changes of ζ-potentials and surface hydrophobicity of PC. Notably, the innermost PC layer was difficult to be proteolyzed. Furthermore, when S. cerevisiae was stimulated by ultrasound + 0.1 mg/mL nano-Se@PC, the proportion of lethal and sublethal injured cells increased as a function of the proteolysis time of PC. The transcriptomics analysis revealed that 34 differentially expressed genes which varied monotonically were related to the plasma membrane, fatty acid metabolism, glycerolipid metabolism, etc. Significant declines in the membrane potential and proton motive force disruption of membrane were found with the prolonged proteolysis time; meanwhile, higher membrane permeability, membrane oxidative stress levels, membrane lipid fluidity, and micro-viscosity were triggered.
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OBJECTIVE: To clinically evaluate the effectiveness of icon infiltration resin on masking post-orthodontic white spots. METHODS: Eight post-orthodontic patients with 6 maxillary anterior teeth showing signs of decalcification (total 48 teeth) were enrolled in this study. All teeth were treated with icon resin infiltration according to manufacturer's recommendation. Standardized digital photographs were taken before, immediately after and 1 week, 6 and 12 months after treatment. Before taking pictures the assigned teeth were cleaned using pumice and rubber polishing cups. The results were classified into three groups: completely masked, partially masked, and unchanged. Pictures of partially masked teeth were analyzed using image analysis software (Image-pro plus 6.0), size of the white spot lesion (W) and the whole tooth facial surface (T) were measured, then W/T ratio (in %) was calculated. The images were imported into image analysis software (Photoshop) which presented the images into histograms of gray scale from (0 to 255). RESULTS: Among the 48 teeth, 11 teeth (22.9%, 11/48) were classified as completely masked, whereas 37 teeth (77.1 %, 37/48) were classified as partially masked and no tooth unchanged. For partially masked teeth, W/T ratio decreased significantly after treatment from 31.37% to 7.99% (by Wilcoxon's signed rank test, P<0.05). The means at gray scale for the initial and 1 week photographs after treatment were 188.07± 5.62 and 143.20± 7.03 respectively, and there was significant difference by Wilcoxon,s signed rank test (P<0.05). The data of 6 and 12 months after treatment were 136.33± 4.54 and 139.57± 3.70 respectively, there were no significant differences (P>0.05) in comparison to 1 week after treatment. CONCLUSION: Resin infiltration was proven to be an effective treatment for masking white spot lesions. The surface color of infiltrated lesions remained stable after 12 months.
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Caries Dental/prevención & control , Esmalte Dental/patología , Soportes Ortodóncicos/efectos adversos , Resinas Sintéticas/química , Grabado Ácido Dental/métodos , Adolescente , Caries Dental/patología , Estética Dental , Femenino , Humanos , Incisivo/patología , Masculino , Desmineralización Dental/tratamiento farmacológico , Desmineralización Dental/etiologíaRESUMEN
OBJECTIVE: To evaluate the effect of infiltration resin on masking white spot lesions by assessing the change in the white spot area. METHODS: Seventy-four maxillary anterior teeth with post-orthodontic decalcification teeth were investigated in this study. All teeth were treated with infiltration resin according to manufacturer recommendation. Standardized digital images were taken before, immediately after, and one week after treatment. The results were classified into three groups: com-pletely masked, partially masked and unchanged. The images of partially masked teeth were analyzed using an image analysis software. The size of the white spot lesion (W) and the whole-tooth facial surface (T) were measured, and the W:Tratio (%) was calculated. Statistical evaluation of the lesions was performed using Kruskal-Wallis and Mann-Whitney tests. RESULTS: Among the 74 teeth, 20 (27%) teeth were classified as completely masked and 54 (73%) teeth were classified as partially masked; no tooth was unchanged. The W:T ratio significantly decreased from 39.28% before treatment to 9.46% after treatment (P < 0.05). CONCLUSION: Resin infiltration is an effective treatment for masking white spot lesion. However, the masking effect depends on the lesion depth and activity.