1.Effect of Icariin on Myocardial Remodeling in Rats Based on Vitamin D Regulation of Dendritic Cell Phenotype
Qian LI ; Yujia CHEN ; Yan ZHOU ; Wen LI ; Liancheng GUAN ; Huanzhen WANG ; Yunzhi CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):76-85
ObjectiveTo investigate the effect of icariin (ICA) on the phenotype of dendritic cells (DCs) in heart tissue of the Dahl salt-sensitive myocardial remodeling model of rats and its regulation on the vitamin D system. MethodsMale Dahl salt-resistant rats were divided into a normal group, and male Dahl salt-sensitive rats were divided into a model group, low-, medium-, and high-dose ICA groups (30, 60, 120 mg·kg-1·d-1), and Vitamin D group (3×10-5 mg·kg-1·d-1). In addition to the normal group, the other groups were given an 8% high salt diet to establish a myocardial remodeling model and received intragastric administration after successful modelling once a day for six weeks. The dynamic changes in tail artery blood pressure were monitored, and detection of cardiac ultrasound function in rats was performed. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the morphological changes in rat heart tissue. The phenotype of DCs and T helper cell 17 (Th17)/regulatory T cell (Treg) ratio were detected by flow cytometry. The mRNA and protein expression of vitamin D receptor (VDR), 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), forkhead frame protein 3 (FoxP3), solitaire receptor γt (RORγt), myocardial type Ⅰ collagen (ColⅠ), and type collagen (ColⅢ) in heart tissue was detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared with the normal group, the model group showed disordered arrangement and rupture of myocardial cells, nuclear condensation, significant edema of myocardial tissue, significant proliferation of collagen fibers in a network distribution, and a significant increase in tail artery blood pressure, left ventricular end diastolic diameter (LVEDD), and left ventricular end systolic diameter (LVESD) (P<0.05). The phenotype of cardiac DCs was CD40, CD80, and CD86, and the levels of major histocompatibility complex Ⅱ (MHC-Ⅱ), Th17 cells, and Th17/Treg were significantly increased (P<0.05). The mRNA and protein expression of CYP24A1 and RORγt in the heart, as well as the mRNA expression of ColⅠ and ColⅢ, were significantly increased (P<0.05). The left ventricular ejection fraction (LVEF), interventricular septal thickness (IVSD), and left ventricular posterior wall thickness (LVPWD) were significantly decreased (P<0.05). The phenotype of cardiac DCs such as CD11, CD11b, and Treg cells, were significantly reduced (P<0.05), while the mRNA and protein expression of cardiac VDR, CYP27B1, and FoxP3 were significantly decreased (P<0.05). Compared with the model group, the low-, medium-, and high-dose ICA groups and vitamin D group significantly reduced myocardial cell rupture and nuclear consolidation in rats. The high-dose ICA group and vitamin D group showed a small amount of myocardial cell rupture and nuclear consolidation, improving myocardial fiber arrangement to varying degrees and significantly reducing myocardial fiber rupture and proliferation. The tail artery blood pressure, LVEDD, and LVESD were significantly decreased in the low-, medium-, and high-dose ICA groups and vitamin D group (P<0.05), and the phenotype of cardiac DCs including CD40, CD80, CD86, MHC-Ⅱ, Th17 cells, and Th17/Treg were significantly decreased (P<0.05). The mRNA and protein expression of CYP24A1 and RORγt, and the mRNA expression of ColⅠ and ColⅢ in the heart were significantly decreased in the medium- and high-dose ICA groups and vitamin D group (P<0.05). The LVEF, IVSD, and LVPWD of myocardial remodeling model rats in the low-, medium-, and high-dose ICA groups and vitamin D group were significantly increased (P<0.05). The phenotypes of cardiac DCs including CD11, CD11b, and Treg cells were significantly increased in the medium- and high-dose ICA groups and the Vitamin D group (P<0.05). The mRNA and protein expressions of VDR, CYP27B1, and FoxP3 in the heart were significantly increased in the medium- and high-dose ICA groups and vitamin D group (P<0.05). ConclusionICA can regulate tail artery blood pressure, cardiac structural and functional damage, and myocardial tissue fibrosis and inhibit phenotype and functional maturation of DCs in heart tissue in the myocardial remodeling model of Dahl salt-sensitive rats. It can also affect the gene and protein expression of VDR, CYP24A1, and CYP27B1, achieving its intervention in Th17/Treg balance in the immune process of myocardial remodeling possibly by regulating vitamin D/VDR in heart tissue.
2.Comorbidity and associated factors of overweight/obesity and dental caries among primary and secondary school students in Guangxi
LUO Yuemei, REN Yiwen, CHEN Li, DONG Yonghui, YUAN Wen, MA Jun, DONG Yanhui, LI Yan, ZHOU Weiwen
Chinese Journal of School Health 2025;46(4):485-488
Objective:
To explore the comorbidity and associated factors of dental caries and overweight/obesity among primary and secondary school students in Guangxi, so as to provide a scientific basis for the development of targeted prevention strategies.
Methods:
A stratified cluster random sampling method was used to survey 178 700 students from the fourth grade of primary school to the third year of high school in Guangxi Zhuang Autonomous Region from September to November 2023, including physical examination, oral screening, and questionnaire survey. Chisquare tests and binary Logistic regression analysis were employed to investigate the related factors of the cooccurrence of dental caries and overweight/obesity among students.
Results:
The comorbidity rate of dental caries and overweight/obesity was 9.55%, with urban areas (9.95%) higher than rural counties (9.24%), boys (10.54%) higher than girls (8.54%), primary school students (11.49%) higher than senior high school students (8.92%) and junior high school students (8.05%), and nonboarding students (11.44%) higher than boarding students (7.94%), and all differences were statistically significant (χ2=26.07, 207.91, 471.54, 629.14,P<0.01). Multivariate Logistic regression analysis showed that consuming cereal for breakfast (OR=0.91, 95%CI=0.88-0.94), drinking milk in the past week (OR=0.89, 95%CI=0.83-0.95), meeting sleep standards (OR=0.95, 95%CI=0.91-0.99), and brushing teeth at least once a day (OR=0.82, 95%CI=0.73-0.93) had a lower risk of the comorbidity of dental caries and overweight/obesity. In contrast, drinking beverages in the past week (OR=1.14, 95%CI=1.09-1.20), consuming fried foods in the past week (OR=1.11, 95%CI=1.06-1.17), eating fruit ≥1 time every day (OR=1.06, 95%CI=1.02-1.11), consuming fruit ≥1 type every day (OR=1.07, 95%CI=1.01-1.12), and having fish, poultry, meat, or eggbased breakfasts (OR=1.03, 95%CI=1.05-1.13) had a higher risk of the comorbidity of dental caries and overweight/obesity (P<0.05).
Conclusions
Dietary habits and lifestyle behaviors are associated with the comorbidity of dental caries and overweight/obesity among primary and secondary school students in Guangxi. Guiding students to form healthy living habits is helpful to preven dental caries and overweight/obesity.
3.Analgesic effect of dezocine combined with ropivacaine on patients undergoing thoracoscopic radical resection of lung cancer
Zhi-Guo YI ; Wen ZHOU ; Yan-Ping SU ; Fang TANG ; Jian-Dong DENG
The Chinese Journal of Clinical Pharmacology 2024;40(8):1116-1120
Objective To explore the analgesic effect of different doses of dezocine combined with ropivacaine for thoracic paravertebral block(TPVB)on patients undergoing thoracoscopic radical resection of lung cancer and the influence on hemodynamics and immune function of patients.Methods Patients with lung cancer who underwent thoracoscopic radical resection were divided into low-dose group and high-dose group according to random number table method.Both groups of patients were given total intravenous anesthesia to complete the surgery.At 15 min before general anesthesia induction,the low-dose group was given TPBV with 0.1 mg·kg-1 dezocine+0.375%ropivacaine for a total of 20 mL,and the high-dose group was given TPBV with 0.15 mg·kg-1 dezocine+0.375%ropivacaine for a total of 20 mL.Comparisons were performed on both groups in terms of analgesic effect,hemodynamic parameters,immune function and occurrence of adverse drug reactions.Results There were 48 cases in low-dose group and 46 cases in high-dose group.In low-dose group,the heart rate values before TPVB,before skin incision,at 5 min after sectioning and at the end of surgery were(78.52±6.54),(70.79±7.07),(74.48±6.68)and(76.69±7.29)beat·min-1,the mean arterial pressure values were(93.16±5.72),(86.38±7.51),(92.15±6.36)and(91.14±6.13)mmHg.In high-dose group,the heart rate values at the above time points were(79.36±7.11),(71.68±6.49),(74.76±7.06)and(76.57±6.52)beat·min-1;the mean arterial pressure values were(93.89±7.18),(85.27±7.41),(90.34±6.52)and(92.43±6.34)mmHg,there were no statistical differences between the two groups(all P>0.05).The resting state scores at 2,6 and 12 h after surgery were(1.38±0.19),(1.54±0.21)and(1.72±0.16)points,the pain scores at motion state were(1.88±0.15),(2.36±0.37)and(3.26±0.38)points in low-dose group;in high-dose group,the resting state scores were(1.32±0.17),(1.58±0.22)and(1.81±0.18)points,the pain scores at motion state were(1.81±0.13),(2.11±0.31)and(3.03±0.36)points,respectively,there were no statistical differences between the two groups(all P>0.05).The number of analgesic pump compressions at 24 h after surgery and the number of cases with analgesic remedy were(5.12±1.26)times and 15 cases in low-dose group and were(4.74±1.03)times and 10 cases in high-dose group,with no statistical differences between the groups(all P>0.05).The percentages of CD3+cells in low-dose group at the end of surgery and at 12 h and 24 h after surgery were(68.51±6.76)%,(54.22±5.43)%and(51.47±6.58)%,the percentages of CD4+cells were(40.29±5.02)%,(34.94±4.79)%and(30.48±5.11)%,CD4+/CD8+ratios were 1.54±0.34,1.36±0.28 and 1.16±0.23;the percentages of CD3+cells in high-dose group were(67.92±7.11)%,(56.58±6.36)%and(54.47±6.89)%,percentages of CD4+cells were(41.33±5.75)%,(35.86±5.21)%and(32.27±4.78)%,the CD4+/CD8+were 1.53±0.35,1.40±0.30 and 1.22±0.26,all with no significant difference(all P>0.05).The incidence of postoperative adverse drug reactions in high-dose group and low-dose group were 32.61%and 14.58%,with significant difference(P<0.05).Conclusion When TPVB regimen of dezocine combined with ropivacaine is used in thoracoscopic radical resection of lung cancer,the analgesic effect of low-dose dezocine is comparable to that of high-dose dezocine,with lower risk of adverse drug reactions.
4.Anti-SARS-CoV-2 activity of small molecule inhibitors of cathepsin L
Wen-wen ZHOU ; Bao-qing YOU ; Yi-fan ZHENG ; Shu-yi SI ; Yan LI ; Jing ZHANG
Acta Pharmaceutica Sinica 2024;59(3):600-607
The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC50) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process.
5.Study on the Distribution of Traditional Chinese Medicine Constitution in Pregnant Women with Iron Deficiency Anemia and Its Influencing Factors
Ying WANG ; Jing-Wen ZHOU ; Ye-Yao YANG ; Li-Shan SU ; Yan-Fang LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):21-26
Objective To investigate the distribution of traditional Chinese medicine(TCM)constitution in pregnant women with iron deficiency anemia(IDA)and its related influencing factors,so as to provide a reference for the TCM prevention and treatment of IDA in pregnancy.Methods A total of 109 eligible patients with IDA during pregnancy were included in the study.The general data of pregnant women,the TCM constitution types and relevant laboratory indicators including serum ferritin(Fer),hemoglobin(Hb)and mean corpuscular volume(MCV)were collected.Statistical analyses were conducted on the distribution of TCM constitution types of IDA pregnant women and its related influencing factors as well as the pregnancy outcomes.Results(1)The 109 IDA pregnant women were predominated by biased constitution types,accounted for 60 cases(55.05%).The distribution of the constitution types of 109 IDA pregnant women was as follows:balanced constitution(49 cases,44.95%)>damp-heat constitution(13 cases,11.93%)>yang deficiency constitution(12 cases,11.01%)>yin deficiency constitution(11 cases,10.09%)>qi deficiency constitution(10 cases,9.17%)>qi stagnation constitution(9 cases,8.26%)>blood stasis constitution(3 cases,2.75%)>phlegm-damp constitution(2 cases,1.83%).(2)Comparison of Hb and MCV levels in IDA pregnant women with various constitution types showed no statistically significant differences(P>0.05),but Fer level in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution(P<0.01),and the probability of occurrence of amniotic opacity in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution and other biased constitution types(P<0.05).Conclusion Damp-heat constitution is the most common TCM constitution type in pregnant women with IDA,followed by yang deficiency constitution,yin deficiency constitution and qi deficiency constitution.The damp-heat constitution may be the susceptible constitution of pregnant women with IDA,and IDA pregnant women with damp-heat constitution have significantly higher Fer level than those with balanced constitution,and also have the higher probability of occurrence of amniotic opacity than those with balanced constitution and other biased constitution types.
6.Comparison of the predictive value of new simplified insulin resistance assessment indexes in identifying left ventricular subclinical dysfunction in T2DM patients
Yan-Yan CHEN ; Meng-Ying LI ; Jie ZHOU ; Jian-Fang FU ; Ying ZHANG ; Yi WANG ; Cheng WANG ; Xiang-Yang LIU ; Sheng-Jun TA ; Li-Wen LIU ; Ze-Ping LI ; Xiao-Miao LI
Medical Journal of Chinese People's Liberation Army 2024;49(2):137-143
Objective To investigate the predictive value of new simplified insulin resistance(IR)assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction(LVEF≥50%)who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed.All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain(GLS).According to GLS value,the subjects were divided into the normal group(GLS≥18%group,n=80)and the impaired group(GLS<18%group,n=70).Some new simplified IR assessment indicators were calculated and compared between the two groups,including body mass index(BMI),TG/HDL-C ratio,triglyceride-glucose(TyG)index,TyG-BMI index,TyG-WHR and metabolic score for IR(METS-IR).Correlation between the GLS and the new simplified IR assessment indexes was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes,with the area under the curve(AUC)calculated.Furthermore,according to whether the subjects were complicated with hypertension,binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS<18%.Results Total 150 were included with aged(54.5±13.7)years with 96(64.0%)men and 54(36.0%)women.Compared with the GLS≥18%group,the TG/HDL-C ratio,TyG index,TyG-BMI,and METS-IR of subjects in the GLS<18%group were significantly increased(P<0.05).Pearson correlation analysis showed that TG/HDL-C ratio,TyG index,TyG-BMI,TyG-WHR,and METS-IR were negatively correlated with GLS(P<0.05).ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18%(AUC=0.678,95%CI 0.591-0.765,P<0.001).Stratification based on hypertension and further adjusting for confounding factors,TyG index remains significantly associated with GLS<18%(OR=3.249,95%CI 1.045-10.103,P=0.042).Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction.TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.
7.Characteristics of T cell immune responses in adults inoculated with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months
Jing WANG ; Ya-Qun LI ; Hai-Yan WANG ; Yao-Ru SONG ; Jing LI ; Wen-Xin WANG ; Lin-Yu WAN ; Chun-Bao ZHOU ; Xing FAN ; Fu-Sheng WANG
Medical Journal of Chinese People's Liberation Army 2024;49(2):165-170
Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.
8.The effect of cuproptosis related gene methylation on the prognosis of cervical cancer
Yu DING ; Jiaqi PENG ; Jinhui CHEN ; Zhiwei ZHOU ; Qian WU ; Ping LI ; Yuli LIU ; Ping TAN ; Yan HU ; Xiaobing XIE ; Dingsheng WEN
Chinese Journal of Laboratory Medicine 2024;47(4):407-412
To investigate the differences in methylation levels of cuproptosis related genes in cervical cancer and their effects on clinical prognosis.Methods:The methylation data of 310 cervical tissue specimens were acquired from public databases. The UALCAN database was used to analyze the methylation level differences of 12 cuproptosis-related genes and study their level in different stages or grades of cervical cancer. Genes with statistically significant differences were selected for prognosis analysis using the EWAS datahub. Finally, gene-enrichment analysis, pathway analysis, immune infiltration analysis, the mutation rate and tumor mutation burden (TMB) of the genes in cervical cancer were analyzed using the cBioportal database. Two independent samples rank-sum test was used for differences in methylation levels and immune cell infiltration; comparative analyses of overall survival were performed using KM survival curves and Log-rank two-sided tests. TMB analyses were performed using the Wilcoxon Test for statistical analyses; Pearson correlation analysis was used for assessment in GSEA and pathway analyses.Results:The methylationβvalue of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A gene) in the cervical cancer tissues of patients was 0.075 which was significantly higher than the methylationβvalue of 0.049 in normal human tissues ( P=0.008). Dihydrolipoamide S-Acetyltransferase (DLAT gene) methylation with a β value of 0.102 was significantly higher than normal human tissue methylation with a β value of 0.08 ( P=0.002), and the methylation level β value of Lipoyltransferase 1 (LIPT1 gene) in cervical cancer tissues was 0.06,which was significantly lower than normal human tissue methylation value of 0.092 ( P=0.009). Patients with CDKN2A gene methylation levels≥0.199 had an overall survival of 14.75 years, which was lower than that of patients with methylation levels<0.199 (17.56 years) ( P=0.034).The results of gene enrichment analysis indicated that it mainly involves biological processes such as the response to type I interferon and DNA replication. The expression of CDKN2A gene is positively correlated with the number of neutrophils and dendritic cells in the tumor microenvironment( P<0.05), and negatively correlated with the number ofmacrophages( P<0.05). TMB was higher in the group of variants of the CDKN2A gene than in the group of non-variants ( P=0.019). Conclusion:CDKN2A methylation is a potential biomarker for predicting the prognosis of cervical cancer.
9.Antiviral Efficacy and Mechanism of BD-77 Against Novel Coronavirus SARS-CoV-2
Lei BAO ; Qinhai MA ; Shanshan GUO ; Ronghua ZHAO ; Wen XIA ; Zihan GENG ; Jing SUN ; Yanyan BAO ; Zhou XU ; Shenglong YAN ; Jinxin XIAO ; Huarong CHEN ; Chenggang HUANG ; Xiaolan CUI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):45-51
ObjectiveThe human angiotensin converting enzyme2 (hACE2) transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus (Delta/Omicron) to angiotensin converting enzyme2 (ACE2). Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group, SARS-CoV-2 infection group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1, with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice, detect the virus titer of the lung tissue of the mice, and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro, with median inhibitory concentration (IC50) of 526.3 mg·L-1 and 653.0 mg·L-1, respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT, Omicron, and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died, while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1 could reduce the mortality of mice, significantly lower the virus titer in the lung tissue of mice (P<0.05), and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However, its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.
10.Effect of Icariin on Peripheral Blood Dendritic Cells and Th17/Treg Balance in Myocardial Remodeling Model of Dahl Salt-sensitive Rats
Qian LI ; Yan ZHOU ; Yujia CHEN ; Wen LI ; Huanzhen WANG ; Liancheng GUAN ; Yunzhi CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):46-55
ObjectiveTo investigate the effect of icariin (ICA)-mediated vitamin D system on peripheral blood dendritic cells (DCs) and helper T cells 17 (Th17)/regulatory T cells (Treg) balance in myocardial remodeling model of Dahl salt-sensitive rats. MethodFifty SPF Dahl salt-sensitive rats were divided into model group, vitamin D group (3×10-5 mg·kg-1·d-1), and high-, medium-, and low-dose ICA groups (120, 60, 30 mg·kg-1·d-1), and 10 Dahl salt-resistant rats were used as normal group. The myocardial remodeling model was established by feeding rats with a high-salt diet containing 8% NaCl. After six weeks of modeling, the normal group and the model group were given an equal volume of ultrapure water by gavage, and other groups were continuously administrated for six weeks. Cardiac echocardiography, hematoxylin-eosin (HE) staining, and Masson staining were used to observe the pathological changes in cardiac structure and fibrosis. The levels of serum 25(OH)D3, B-type N-terminal pro-brain natriuretic peptide (NT-ProBNP), interleukin (IL)-17, transforming growth factor (TGF)-β1, IL-12, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). The phenotype of peripheral blood DCs and the ratio of Th17/Treg cells of rats were detected by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expressions of vitamin D receptor (VDR),1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) in peripheral blood DCs of rats. ResultCompared with the control group, the rats in the model group had pathological changes such as disordered arrangement of myocardial cells and cytoplasmic hypertrophy and swelling. Myocardial collagen fibers proliferated significantly, and the arrangement of myocardial fibers was disordered. The levels of serum 25(OH)D3 and IL-10 were significantly decreased, and the levels of serum IL-17, TGF-β1, IL-6, IL-12, and NT-ProBNP were significantly increased (P<0.05). The costimulatory molecules CD40, CD80, CD86, and MHC-Ⅱ were highly expressed in the peripheral blood DCs, and the expression of CD11 and CD11b was lower (P<0.05). The proportion of Th17 cells in the peripheral blood was significantly increased, and the proportion of Treg cells was decreased. The ratio of Th17/Treg was increased (P<0.05). The mRNA and protein expressions of CYP24A1 in peripheral blood DCs increased, and the mRNA and protein expressions of CYP27B1 and VDR decreased (P<0.05). Compared with the model group, the arrangement of myocardial fibers in each drug administration group was relatively regular, and the swelling of myocardial cells was significantly reduced. The pathological morphology of myocardial tissue was improved to varying degrees. The pathological changes in myocardial tissue were improved and alleviated to varying degrees. The drug could reduce the serum levels of NT-ProBNP, IL-17, TGF-β1, IL-6, and IL-12 and increase the level of serum 25(OH)D3 and IL-10 (P<0.05). The expression of costimulatory molecules CD40, CD80, CD86, and MHC-Ⅱ in the peripheral blood DCs of rats was decreased, and the expression of CD11 and CD11b molecules was increased (P<0.05). The drug could reduce the proportion of Th17 cells in peripheral blood and the ratio of Th17/Treg cells and increase the proportion of Treg cells (P<0.05). It could decrease the mRNA and protein expressions of CYP24A1 in peripheral blood DCs of rats and elevate the mRNA and protein expression of VDR and CYP27B1 (P<0.05). ConclusionICA can regulate the phenotype of peripheral blood DCs and the ratio of Th17/Treg cells by regulating the vitamin D system and play a role in improving myocardial remodeling from the perspective of immune balance.


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