1.Role of group 2 innate lymphoid cells in mice with atopic dermatitis-like inflammatory response induced by MC903
Ting YANG ; Kaoyuan ZHANG ; Zizhuo LI ; Xu LI ; Bo YU ; Xia DOU
Chinese Journal of Dermatology 2021;54(4):335-341
Objective:To explore the role of group 2 innate lymphoid cells (ILC2) in atopic dermatitis (AD) .Methods:C57BL/6J and Rag1 -/- mice served as research objects. The C57BL/6J mice were divided into 2 groups: model group topically treated with calcipotriol (MC903) on both ears every day for 14 consecutive days, control group topically treated with anhydrous ethanol alone at the same time. On day 15, peripheral blood samples were collected from the mice. After the sacrifice, the ear skin tissues were obtained for histopathological examination, and the spleens were resected. Real-time fluorescence-based quantitative PCR was performed to determine the expression of inflammatory factors in the skin and spleen tissues, and flow cytometry to determine the proportion of ILC2 in the skin tissues. The Rag1 -/- mice were divided into model group, control group and experimental group: the Rag1 -/- mice in the model group and control group received the same treatment and evaluation as the C57BL/6J mice; two days before the topical treatment with MC903, the Rag1 -/- mice in the experimental group started to be intraperitoneally injected with the monoclonal antibody CD90.2 at a dose of 300 μg/150 μl once every other 2 days for 7 sessions, with the purpose of antagonizing the function of ILC2, and other treatments were the same as those in the model group. Skin manifestations were observed, and histopathological features were evaluated. Two-independent-sample t test was used for comparisons between 2 groups, and one-way analysis of variance for comparisons among multiple groups. Results:In the model group, the ear skin of the C57BL/6J mice was apparently red, swollen and dry with crusts, and hematoxylin and eosin (HE) staining showed increased thickness of the epidermis and dermal infiltration of eosinophils; the serum level of IgE (6 751.016 ± 282.324 μg/L) was significantly higher in the model group than in the control group (6 387.038 ± 267.853 μg/L, P= 0.007) , so were the expression of interleukin (IL) -4, IL-13 and interferon (IFN) -γ in the skin tissues ( P= 0.005, 0.012, < 0.001, respectively) , but there was no significant difference in IL-5 expression ( P= 0.190) ; the expression of IL-4, IL-13 and IFN-γ in the spleen was significantly higher in the model group than in the control group (all P < 0.001) , but there was no significant difference in IFN-γ expression ( P= 0.278) ; moreover, the model group showed significantly increased proportion of ILC2 (5.604% ± 2.105%) compared with the control group (1.750% ± 1.104%, P= 0.003) . In the Rag1 -/- mice, the ear skin was obviously red, swelling and dry with crusts in the model group, and HE staining showed increased epidermal thickness and eosinophil infiltration in the dermis; the model group showed significantly increased expression of IL-4, IL-5, thymic stromal lymphopoietin (TSLP) and IL-33 in skin tissues ( P= 0.010, 0.043, 0.034, 0.007, respectively) , but no significant difference in the expression of IL-13 or IFN-γ ( P= 0.274, 0.697, respectively) compared with the control group; the proportion of ILC2 was significantly higher in the model group (5.165% ± 2.436%) than in the control group (0.835% ± 0.578%, P= 0.014) ; the experimental group showed markedly attenuated skin lesions, reduced epidermal thickness and number of eosinophils infiltrating in the dermis, but no significant difference in the expression of IL-4, IL-5, IL-13, TSLP or IL-33 compared with the model group (all P > 0.05) . Conclusion:ILC2 play a role in the mice with AD-like inflammatory response induced by MC903, which dose not depend on adaptive immunity.
2.Analysis on risk factors of thyroid nodule in Harbin City, Heilongjiang Province
Jun HUANG ; Zizhuo LI ; Meixin SHI ; Yujie LI ; Xiuhua YANG
Chinese Journal of Endemiology 2017;36(9):675-678
Objective To analyze the risk factors of thyroid nodule (TN) in Harbin City,Heilongjiang Province.Methods From November 2014 to January 2015,residents lived in Nangang,Daoli,Daowai districts and villagers of Xubao Town of Hulan District of Harbin City were selected as research subjects,who lived in the local regions for more than 5 years,a total of 2 650 people were surveyed.Influence factors of TN were surveyed by general survey,clinical examination and thyroid ultrasound examination.Logistic regression analysis was used to analyze relationships between various factors and TN in single factor analysis and multiple factors analysis.Results Excluding 36 cases with thyroid surgery history,the total prevalence of TN was 22.92% (599/2 614),single factor Logistic regression analysis found that females [odds ratio (OR) =1.597,95% confidence interval (CI) =1.328-1.919],elderly (OR =3.356,95%CI =2.699-4.173),living in cities and towns (OR =1.677,95%CI =1.391-2.021),obesity (OR =1.245,95%CI =1.036-1.497),history of hypertension (OR =1.766,95%CI =1.414-2.205) were the risk factors of TN.In multiple factors Logistic regression analysis,risk factors from high to low in the order were elderly (OR =3.076,95%CI =2.436-3.884),females (OR =1.819,95%CI =1.493-2.215),living in cities and towns (OR =1.701,95%CI =1.400-2.066),history of diabetes (OR =1.644,95%CI =1.235-2.189),obesity (OR =1.325,95%CI =1.085-1.618).Conclusions The risk factors of TN include living in cities and towns,females,elderly,obesity,history of hypertension or diabetes in Harbin City of Heilongjiang Province.
3.Application of erythrocyte energy technique in quantitative assessment of thyroid function in patients with thyroid diffuse lesions
Jihua WANG ; Zizhuo LI ; Minlu YUE ; Xinling DU ; Xiuhua YANG
Chinese Journal of Medical Ultrasound (Electronic Edition) 2018;15(4):268-274
Objective To evaluate the value of color flow angio(CFA)in judging the status of thyroid function by analyzing the ultrasonographic features and quantitatively measuring the blood flow signals in patients with thyroid diffuse lesions.Methods Totally 100 patients with thyroid diffuse lesions diagnosed by ultrasonography between Oct.2016 and Jun.2017 were divided into three groups:hyperthyroidism group(n=30),hypothyroidism group(n=34)and euthyroid group(n=36).Moreover,30 cases of healthy volunteers were chosen as control group.The blood flow index including vascularity index(VI)value and Vascularity value of region of interest from all cases was measured through CFA imaging technique.The differences of VI and Vascularity from above 4 groups were compared using one-way analysis of variance.Comparison among groups was carried out by SNK-q test.The subjects' work curves(ROC curves)were plotted and analyzed using clinical diagnosis as gold standard.At the same time,the correlation between VI and thyroid function in hyperthyroid group and hypothyroidism group was analyzed through Pearson correlation coefficient.Results The levels of VI and Vascularity in hyperthyroid group,hypothyroid group,euthyroid group and control group were decreased gradually with significant differences between every two groups.VI : control vs hyperthyroid,hypothyroid and euthyroid group: q=13.67,7.00 and 3.93,all P<0.01.Euthyroid vs hyperthyroidism and hypothyroid group: q=10.35,P<0.01 and q=3.27,P<0.05.Hyperthyroidism vs hypothyroid group: q=7.09,P<0.01.Vascularity: control vs hyperthyroid,hypothyroid and euthyroid group: q=15.23,10.16 and 6.58,all P<0.01.Euthyroid vs hyperthyroidism and hypothyroid group: q=9.33 and 3.83,both P<0.01.Hyperthyroidism vs hypothyroid group: q=5.55,P<0.01.The area under the curve of hyperthyroidism group and hypothyroidism group was 0.733,with 9.526%as the diagnostic cutoff point.The sensitivity and specificity were 70.0%and 76.5%respectively.The area under the curve of the abnormal group and normal group was 0.768,with 7.404%as the diagnostic cutoff point.The sensitivity and specificity were 62.5%and 88.9%,respectively.The VI value of hyperthyroidism group was positively correlated with FT3 and FT4(r=0.584,0.499,both P<0.05),and negatively correlated with TSH(r=-0.447,P<0.05).The VI value of hypothyroidism group was negatively correlated with FT4(r=-0.342,P<0.05),and had no significant correlation with FT3 and TSH(r=0.121,-0.007,P>0.05).Conclusion CFA imaging technology can quantitatively measure the blood flow signals of thyroid parenchyma and evaluate the thyroid function in patients with thyroid diffuse lesions.
4.Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis.
Kai JIANG ; Yue XU ; Dandan WANG ; Feng CHEN ; Zizhuo TU ; Jie QIAN ; Sheng XU ; Yixiang XU ; John HWA ; Jian LI ; Hongcai SHANG ; Yaozu XIANG
Protein & Cell 2022;13(5):336-359
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive. Here we demonstrated that the SGLT2 inhibitor, Empagliflozin (EMPA), suppresses cardiomyocytes autosis (autophagic cell death) to confer cardioprotective effects. Using myocardial infarction (MI) mouse models with and without diabetes mellitus, EMPA treatment significantly reduced infarct size, and myocardial fibrosis, thereby leading to improved cardiac function and survival. In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated, EMPA directly inhibits the activity of the Na+/H+ exchanger 1 (NHE1) in the cardiomyocytes to regulate excessive autophagy. Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis. In contrast, overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation, which was effectively rescued by EMPA treatment. Furthermore, in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA's cardioprotective effects are at least in part through downregulation of autophagic flux. These findings provide new insights for drug development, specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after MI in both diabetic and non-diabetic patients.
Animals
;
Diabetes Mellitus
;
Diabetes Mellitus, Type 2/drug therapy*
;
Glucose
;
Humans
;
Mice
;
Myocardial Infarction/metabolism*
;
Sodium-Glucose Transporter 2 Inhibitors/therapeutic use*
;
Ventricular Remodeling