الملخص
Objective:To preliminarily investigate the effect of blue light on the biological activity of human skin keratinocytes, fibroblasts and melanocytes.Methods:Discarded foreskin tissues were collected from 10 healthy children aged from 3 to 12 years after circumcision surgery in the First Affiliated Hospital of Kunming Medical University from June 2021 to December 2021. After epidermis-dermis separation, selective culture was performed to isolate keratinocytes, fibroblasts, and melanocytes. According to the pre-experiment results, the above three types of cells were irradiated with 440 - 450 nm blue light at doses of 0, 5, 10, 20, 30, and 40 J/cm 2, and then continued to be cultured for 0, 6, 24, and 48 hours. Cell counting kit 8 (CCK8) assay was performed to evaluate cellular proliferative activity at each time point, enzyme-linked immunosorbent assay (ELISA) to detect levels of interleukin (IL) -18, IL-33, nerve growth factor (NGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by keratinocytes, as well as levels of IL-33 and keratinocyte growth factor (KGF) secreted by fibroblasts, NaOH lysis method to determine melanin synthesis rates in melanocytes, and Western blot analysis to determine the relative expression of tyrosinase (TYR), tyrosine-related protease 1 (TRP-1) and dopachrome isomerase (DCT) in melanocytes. Two-way analysis of variance was used to analyze group effects, time effects and interaction effects. Results:After irradiation with blue light, the cellular proliferative activity significantly differed among different doses of blue light irradiation groups and different time points in keratinocytes ( Ftime = 516.20, Fdose = 421.20, Finteraction = 25.05, all P < 0.003), fibroblasts ( Ftime = 129.30, Fdose = 477.80, Finteraction = 10.91, all P < 0.003), and melanocytes ( Ftime = 77.61, Fdose = 138.70, Finteraction = 3.50, all P < 0.003) ; immediately after irradiation, the proliferative activity of keratinocytes and fibroblasts was significantly lower in the 20 - 40 J/cm 2 blue light group than in the 0 J/cm 2 blue light group (all P < 0.003), and the proliferative activity of melanocytes was significantly higher in the 5 J/cm 2 blue light group than in the 0 J/cm 2 blue light group ( P < 0.003) ; the proliferative activity of the 3 types of cells showed decreasing trends with the increase of blue light irradiation doses and culture time. ELISA showed that the concentrations of IL-18, IL-33, NGF, and GM-CSF secreted by keratinocytes, as well as the concentrations of IL-33 and KGF secreted by fibroblasts, tended to increase with the increase of blue light irradiation doses and culture time. The melanin synthesis rates in melanocytes significantly differed among different doses of blue light irradiation groups and different time points ( Ftime = 833.50, Fdose = 249.40, Finteraction = 81.38, all P < 0.003) ; during 0 - 24 hours after blue light irradiation, the melanin synthesis rates tended to increase with the increase of blue light irradiation doses and time; during 24 - 48 hours, the melanin synthesis rates showed decreasing trends with the increase of blue light irradiation doses and culture time compared with that at 24 hours after irradiation; 24 hours after irradiation, the melanin synthesis rates were significantly higher in the 5, 10, 20, 30 and 40 J/cm 2 blue light groups (159.50% ± 10.88%, 218.76% ± 8.49%, 333.72% ± 7.72%, 393.29% ± 6.00%, 427.21% ± 8.39%, respectively) than in the 0 J/cm 2 blue light group (102.29% ± 6.57%, all P < 0.003). The relative expression of TYR ( Ftime = 67.94, Fdose = 28.99, Finteraction = 3.71, all P < 0.003), TRP-1 ( Ftime = 21.73, Fdose = 8.38, both P < 0.003) and DCT ( Ftime = 34.51, Fdose = 11.79, both P < 0.003) in melanocytes significantly differed among different doses of blue light irradiation groups and different time points, and tended to increase with the increase of blue light irradiation doses and culture time. Conclusion:Blue light irradiation at doses of 5 - 40 J/cm 2 could inhibit the proliferative activity of human skin keratinocytes, fibroblasts, and melanocytes, and the inhibitory effect tended to increase with the increase of blue light irradiation doses, except an enhancing effect on the proliferative activity of melanocytes observed immediately after irradiation with blue light at 5 J/cm 2; additionally, blue light irradiation at 5 - 40 J/cm 2 could enhance the expression of melanin synthesis-related enzymes in melanocytes, and increase the melanin synthesis rate in melanocytes over a short period of time.
الملخص
OBJECTIVE The N-methyl-D-aspartate(NMDA)receptor has been shown to be strongly associ-ated with rapid antidepressant effects.GW043 is a com-pound with a novel structure that we designed and syn-thesized to act on the NMDA receptor(NMDAR).METH-ODS In this study,we first confirmed the target of GW043 using a receptor binding assay.We observed the effect of GW043 on NMDAR currents in vivo and in vitro assays using a membrane clamp technique with a view to characterizing the function of GW043.We investi-gated the antidepressant effect of GW043 in rodent behavioral models such as FST,TST and CUMS.Fur-thermore,we explored the mechanism of GW043 onset using Western blotting,BrdU staining,Golgi staining and electrophysiological techniques.RESULTS GW043 interacts with high affinity only at the NMDAR.Electro-physiological studies have indicated that GW043 is a par-tial agonist of NMDAR.Meanwhile,behavioral experi-ments were conducted to confirm the antidepressant effect of GW043 in rodents.The mechanism study found that GW043 regulate synaptic plasticity through LTP and BDNF/mTOR pathways and increase the number of new-born neurons to cause antidepressant effects.GW043,a partial agonist of NMDAR,reversed depression-like behav-ior in rats by modulating synaptic plasticity,suggesting an antidepressant effect.CONCLUSION The results suggest that GW043 is a partial agonist of NMDA recep-tors and has significant antidepressant effects.
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Objective:To investigate the characteristics of allergen component in dust mite（DM） -induced allergic rhinitis（AR） patients, and provide reference for the diagnosis and treatment of AR. Methods:DM-induced AR patients with or without allergic asthma（AA） who visited the Allergy Department of Tongji Hospital, Huazhong University of Science and Technology between 2021 and 2022 were enrolled. Patients'age, gender, and visual analog scale（VAS） for symptoms were recorded. sIgE and sIgG4 levels of allergen components such as Der f1, Der f2, Der p1, Der p2, Der p7, Der p10, Der p21, and Der p23 were detected using a protein chip method. The sensitization characteristics of the allergen components in the patients were observed, and the correlation between sIgE, sIgG of each component and VAS as well as the component differences between AR and AR with AA（AR&AA） were evaluated. Results:A total of 87 DM-induced AR patients were enrolled, with 42.5% of them were AR&AA, their VAS scores were significantly higher than those of AR patients（6.38±1.95 vs 5.25±1.85, P=0.009 8）. The order of sensitization rates for DM components was as follows: Der p2（82.8%）, Der f2（81.6%）, Der p1（74.7%）, Der f1（70.1%）, and Der p23（35.6%）. The order of positive rates for sIgG4 was: Der p2（21.8%）, Der f2（13.8%）, Der p21（8.0%）, and Der p7（6.9%）. There were no correlation between the sIgE, sIgG4 levels or positive numbers of components and VAS scores, but there were positive correlations between sIgE, sIgG4 concentrations of components. Compared with AR patients, AR&AA patients had higher levels of sIgE for Der p（60.5[7.2-91.1]vs 14.0[4.8-45.1], P=0.02）, Der f（49.8[15.7-81.6]vs 21.3[7.0-50.2], P=0.04）, Der p1（27.2[0.7-51.5]vs 2.6[0.2-24.9], P=0.02）, Der p2（20.0[1.4-60.6]vs 5.5[0.6-19.1], P=0.004）, and Der f2（58.9[16.0-89.2]vs 23.4[0.9-56.8], P=0.009）, and a higher proportion of AR with AA patients had sIgE levels of Der p1（70.3% vs 48.0%, P=0.038） and Der p23（27.0% vs 14.0%, P=0.039） that were ≥3 grades. Conclusion:Der p1/f1, Der p2/f3, and Der p23 are the major components of DM sensitized AR patients. Multiple component sensitization and sIgE, sIgG4 levels of each component are not correlated with the severity of AR. The sIgE levels of the Der p1/f1, Der p2/f3, and Der p23 components in AR&AA patients are higher than AR.
الموضوعات
Animals , Humans , Allergens , Pyridinolcarbamate , Rhinitis, Allergic/therapy , Pyroglyphidae , Asthma , Antigens, Dermatophagoidesالملخص
AIM:To investigate the effects of astragalin(AST)on activation status of astrocytes and the ex-pression level of autophagy-related proteins in the cortex of the anterior cingulate cortex of mice with a complete Freund's adjuvant(CFA)-induced inflammatory pain model.METHODS:Twenty-four 6-month-old male C57BL/6 mice were ran-domly divided into four groups:control group,saline group,CFA model group and CFA+60 mg/kg AST administration group,and six mice in each group.Mice in the AST administration group received 60 mg/kg AST by intraperitoneal injec-tion on a body weight basis for 21 d.The paw withdrawal threshold in each group of mice was evaluated by the von Frey test.The expression levels of autophagy-related factors LC3,p62,ATG12 and beclin-1,and astrocyte activation were de-tected by multiplex immunofluorescence staining in the anterior cingulate cortex of mice in each group.Western blot was used to measure the levels of autophagy-related proteins LC3,p62,ATG12 and beclin-1 in the anterior cingulate cortex of mice in each group.RESULTS:Behavioural tests showed that AST significantly increased mechanical pain thresholds in CFA mice(P＜0.05).The results from multiple immunofluorescent staining showed that AST significantly increased the fluorescence intensity of LC3(P＜0.01),ATG12(P＜0.01)and beclin-1(P＜0.05),attenuated the fluorescence intensi-ty of p62(P＜0.05),and inhibited the activation of astrocytes in the anterior cingulate cortex of CFA mice.Western blot results further confirmed that AST significantly increased the expressions of LC3(P＜0.01),ATG12(P＜0.01),beclin-1(P＜0.01),and decreased the expression of p62(P＜0.05)in the anterior cingulate cortex of CFA mice.CONCLU-SION:AST relieves CFA-induced inflammatory pain of mice,and its analgesic mechanism may be related to the inhibi-tion of activation of cortical astrocytes in the anterior cingulate cortex and the promotion of autophagy in CFA mice.
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OBJECTIVE@#To explore the efficacy of individualized subcutaneous immunotherapy (SCIT) in allergic rhinitis(AR) maintain phase.@*METHOD@#Compare nasal symptom scores (VAS) and special disease scale--nasal conjunctivitis quality of life questionnaire(RQLQ) score after 3 years treatment to evaluate the therapeutic effect of each group and the level of improving patients quality of life. Take patients' blood to detect the serum level of IL-10 by enzyme linked immunosorbent test (enzyme linked immunosorbent assay).@*RESULT@#After 3 years treatment, there was no difference of VAS between the conventional SCIT group and the individualized SCIT group. ELISA results showed that the level of IL-10 was significantly higher in the drug symptomatic treatment group than that in the healthy group, the levels of IL-10 were significantly lower in the conventional SCIT group and the individualized SCIT group than that in the healthy group, but there was no difference between the conventional SCIT and the individualized SCIT group.@*CONCLUSION@#After 3 years treatment, there was no difference between conventional and individualized SCIT groups. But the efficacy of the conventional and individualized SCIT groups were significantly better than that in the drug symptomatic treatment group.
الموضوعات
Humans , Desensitization, Immunologic , Enzyme-Linked Immunosorbent Assay , Injections, Subcutaneous , Interleukin-10 , Blood , Precision Medicine , Quality of Life , Rhinitis, Allergic , Drug Therapy , Surveys and Questionnairesالملخص
Glucocorticoids (GC) are increasingly being used to treat chronic rhinosinusitis, its efficacy and safety are the focus of attention. This article will be divided into chronic rhinosinusitis with nasal polyps and without nasal polyps two subtypes discussed nasal and oral glucocorticoids in the clinical therapeutic efficacy and medication safety.