1. Analysis of anti-inflammation mechanism of zukamu granules based on network pharmacology and hs-spme-gc-ms
Journal of International Pharmaceutical Research 2019;46(6):441-455
Objective: To explore the material basis and anti-inflammatory mechanisms of Zukamu granules (ZKMG)based on the headspace-solid phase microextraction-gas chromatography-mass spectrometry(HS-SPME-GCMS) technique and network pharmacology analyses. Methods: HS-SPME-GC-MS technique was used to extract and identify the volatile components of ZKMG. Then combined with the non-volatile components obtained by literature retrieval, we constructed the main chemical composition table. The bioactive components were screened based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and their targets were predicted by the Swiss Target Prediction database. Thereafter, the anti-inflammatory-related targets were screened based on the Thera- peutic Targets Datebase and DrugBank with”Anti-inflammatory”as keyword. Then, the STRING database to analyze protein-protein interaction(PPI)and the software of Cytoscape 3.6.1 was used to construct the component-target-antiinflammatory target network. Finally, enrichment of function and signaling pathways of the target genes was conducted by Gene Ontology(GO)database and the Database for Annotation, Visualization and Integrated Discovery(DAVID). Re- sults: Thirty bioactive components including thymol, kaempferol and quercetin in ZKMG were screened out. Ninety-seven targets were predicted and AKR1B1, ALOX15, ALOX5, CYP1A2, EGFR, CHRM1, NOS3, PLA2G1B, PTGS2, BCHE were key anti-inflammatory targets. Sixty-eight pathways related to anti-inflammation were obtained by KEGG enrichment analysis, mainly including arachidonic acid metabolism, MAPK signaling pathway, inflammatory mediator regulation of TRP channels, IL-17 signaling pathway and NF-κB signaling pathway. Conclusion: This study focuses on the chemical constituents of ZKMG and network pharmacology to predict the material basis and pharmacological mecha- nism of their anti-inflammatory effect, which lays a good foundation for the verification of the later biological experiments and provides certain reference basis for the research on the anti-inflammation mechanism of other compound preparations.
2.Three-dimensional finite element analysis of the change of cracks in the cracked first mandibular molar under different loading conditions.
Tie-zhou HOU ; Feng-yan ZHU ; Hong TAO ; Shuai-shuai WANG
West China Journal of Stomatology 2009;27(2):126-134
OBJECTIVETo study the change of the cracks and the influence on overall displacement of the cracked first mandibular molar under different loadings.
METHODSThree-dimensional finite element models of first mandibular molar with cracks of different depth and length and a control model with no crack were created firstly. Then six loading conditions were applied to the models simulating the real mastication. The changes of the cracks and displacement of the teeth under the six loadings conditions were obtained by finite element method.
RESULTSThe length and depth of the cracks increased, the cracks of the occlusal surface become wider, and the crack was the widest under the fourth loading condition. Moreover, the edge of the cracks was irregular. The adjacent nodes were not in the same plane. The crack of the distal surface was the widest under the sixth loading condition. Compared to the teeth without cracks, the overall displacement of the teeth with cracks increased, but the increment was limited.
CONCLUSIONThe change of the cracks is closely related to the initial crack forms and loading conditions.
Dental Stress Analysis ; Finite Element Analysis ; Humans ; Mastication ; Molar ; Tooth ; Tooth Fractures
3.Relationship between anogenital distance and cryptorchidism in human newborns.
Da-peng JIANG ; Hong-quan GENG ; Hou-wei LIN ; Yu XI-NA ; Xi-wei ZHANG ; Shu-long YANG ; Shuai WANG
National Journal of Andrology 2015;21(5):432-435
OBJECTIVETo explore the relation of the anogenital distance (AGD) with cryptorchidism in male newborns.
METHODSThis study included 350 male infants delivered in two community hospitals between September 2013 and September 2014. Within 24 hours after birth, a pediatric surgeon measured the AGD of the neonates and determined whether they had cryptorchidism. According to the testicular position, we divided the undescended testes into three types: upper scrotal, inguinal, and non-palpable.
RESULTSTotally 39 cases of cryptorchidism were found in the 350 newborns. The AGD of the cryptorchidism infants was significantly shorter than that of the normal neonates ([2.01 ± 0.22] vs [2.35 ± 0.19] cm, P < 0.01), and statistically significant differences remained even when preterm and low birth-weight infants were excluded ([2.32 ± 0.14] vs [2.06 ± 0.19] cm; (2.37 ± 0.17) cm vs (2.12 ± 0.12) cm, all P < 0.01). The newborns with higher-position cryptorchidism had a shorter AGD, though with no significant difference (F = 0.434, P > 0.05). No significant differences were observed in the AGD between unilateral and bilateral cryptorchidism ([1.96 ± 0.13] vs [2.02 ± 0.17] cm, P > 0.05).
CONCLUSIONShorter AGD is associated with a higher incidence of cryptorchidism in male newborns. AGD could serve as a potential biomarker for disruption of androgen action during the male programming window period.
Androgens ; physiology ; Cryptorchidism ; diagnosis ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Male ; Perineum ; abnormalities
4.The roles of PPARs and PPARγ coactivator-1 alpha in mitochondrial cardiomyopathy
Shuai JIANG ; Jie HOU ; Hong LIU ; Dandan LI
Chinese Journal of Endemiology 2018;37(11):943-946
In mitochondria,peroxisome proliferator activated receptor (PPARs) and PPARγ coactivator-1 alpha (PGC-1α) work together to regulate the energy metabolism.Mitochondrial cardiomyopathy is a disease characterized by myocardial damage and abnormal energy metabolic that results from abnormalities in mitochondria quantity,structure and function in cardiac myocytes.However,there is inadequate knowledge on the pathogenesis of mitochondrial cardiomyopathy.In this paper,we summarize the roles played by PPARs and PGC-1α in mitochondrial cardiomyopathy.We expect this paper will provide some new clues for further studies of mitochondrial cardiomyopathy.
5.Therapeutic Effect and Antioxidant Mechanism of Xiaochuanning Granule on Psychological Stress Related Asthma in Rats
Dan HOU ; Shuai-yang HUANG ; Ming-sheng LYU ; Xue-feng GONG ; Hong-sheng CUI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(2):55-61
ObjectiveTo observe the therapeutic effect and antioxidant mechanism of Xiaochuanning granule on psychological stress-related asthma in rats. MethodThe 6-week-old male SD rats were randomly divided into the normal group, asthma group, stress group, stress-related asthma group, western medicine group (atomization of budesonide suspension) and traditional Chinese medicine (TCM) group (Xiaochuanning granule 2.48 g·kg-1). The asthma model was established during 28 days by intraperitoneal injection of 10% ovalbumin(OVA)on the 1st and 8th days and inhaling of vapourized 1% OVA started at the 15th day. Stress group, stress-related asthma group, western medicine group and TCM group were given restraint stimulation during the 28 days to establish the psychological stress-related asthma model. Rats in each group were administered with corresponding drug for 14 days from the 15th day. The sucrose preference test and open field test were performed at the 15th and 28th days. At the end of experiment, the body weight, serum interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13) levels, as well as the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) in lung tissues were detected by assay kits. Hematoxylin-eosin(HE) staining was conducted to observe the pathological changes in lung tissues. Meanwhile, Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) in lung tissues. ResultCompared with the stress-related asthma group, the body weight, sugar water consumption rate and open field distance in the TCM group were significantly increased (P<0.05), and the serum IL-4, IL-5, IL-13 levels were significantly decreased (P<0.05), the levels of SOD and GSH in lung tissues increased significantly (P<0.05), while the level of MDA decreased significantly (P<0.05). HE staining showed that the bronchial mucosal injury, inflammatory cell infiltration, gland hyperplasia, epithelial degeneration and necrosis were significantly ameliorated in the TCM group than in the stress-related asthma group. The expression of Nrf2 and HO-1 protein in lung tissues also increased significantly (P<0.05). ConclusionXiaochuanning Granule can regulate the psychological stress state of stress-related asthmatic rats, alleviate airway inflammatory reaction, and suppress oxidation, which is related to its up-regulation of the Nrf2/HO-1 protein expression.
6.Effect and Mechanism of Sangmei Zhike Granule on Airway Inflammation in Rats with Cough Variant Asthma
Dan HOU ; Shuai-yang HUANG ; Ming-sheng LYU ; Hong-sheng CUI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(2):62-66
ObjectiveTo explore the effect and mechanism of Sangmei Zhike granule (SMZK) on airway inflammation in rats with cough variant asthma(CVA). MethodSix-week-old male SD rats were randomly divided into normal group, model group, and SMZK (2.48 g·kg-1) group. The rats in the model group and the SMZK group received intraperitoneal injection of a mixed solution containing 10% ovalbumin (OVA) and aluminium hydroxide on the 1st and 8th days and aerosol inhalation of 1% OVA solution from the 15th day for CVA model induction. The intervention lasted for two weeks from the 15th day. At the end of animal manipulation, the lung function was detected and inflammatory cells in the peripheral blood were counted. The serum interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-10 (IL-10) levels were determined. Hematoxylin-eosin (HE) staining was performed on the lungs. Western blot was used to detect the protein expression of nuclear factor kappa-B (NF-κB) and its inhibitor α(IκBα) in lung tissues. ResultCompared with the normal group, the model group showed reduced forced expiratory volume in the first 0.1 second (FEV0.1),FEV0.1/forced vital capacity (FVC),and forced expiratory flow 50% (FEF50%) (P<0.05, P<0.01), increased white blood cells and eosinophils (P<0.01), and up-regulated serum IL-4, IL-5, and IL-10 (P<0.01). As revealed by HE staining, the model group displayed shed epithelial cells of the bronchus, airway stenosis, hyperplasia and expansion of mucous glands, disarrangement of layer structures, disorderly arranged cells, and extensive infiltration of inflammatory cells. The protein expression of NF-κB p65 was higher (P<0.01) and that of IκBα was lower (P<0.01) in the lung tissues of the model group than that in the normal group. Compared with the model group, the SMZK group showed increased FEV0.1,FEV0.1/FVC,and FEF50% (P<0.05), decreased white blood cells and eosinophils in the peripheral blood (P<0.01), and declining serum IL-4, IL-5, IL-10 (P<0.01). HE staining demonstrated mild bronchial mucosal injury and relieved inflammatory cell infiltration, gland hyperplasia, and epithelial degeneration and necrosis in the SMZK group. The protein expression of NF-κB p65 was decreased (P<0.05) and that of IκBα was increased (P<0.05) in lung tissues of the SMZK group than that in the model group. ConclusionSMZK can improve lung function and inhibit airway inflammation in rats with CVA. The underlying mechanism may be related to the regulation of IκBα/NF-κB protein expression in the lungs.
7.Network Meta-analysis of Efficacy of Five Classical Prescriptions for Acute Attack of Asthma in Children
Shi-yu ZHANG ; Gui-rui HUANG ; Dan HOU ; Ming-sheng LYU ; Shuai-yang HUANG ; Zhi-jie ZHANG ; Hong-sheng CUI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(2):67-78
ObjectiveTo compare and evaluate the clinical efficacy of five classical prescriptions for acute attack of bronchial asthma (BA) and cough variant asthma (CVA) in children, and to further compare and assess the effect of them on cold-induced asthma or heat-induced asthma. MethodRandomized controlled trials (RCT) on the treatment of acute attack of asthma with five classical prescriptions (Sanzi Yangqintang, Maxing Shigantang, Shegan Mahuangtang, Xiao Qinglongtang, and Dingchuantang) were retrieved from China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), and Wanfang Data (from establishment to August 15, 2021). The eligible RCT were evaluated and the data were extracted for network Meta-analysis by Stata 16.0. ResultA total of eligible 47 RCT were screened out, involving 5 114 children with acute attack of asthma and 10 intervention measures. Among them, 16 RCT (1 912 children, 6 intervention measures) were about the cold-induced asthma and 10 RCT (1 054 cases, 4 intervention measures) focused on the heat-induced asthma. According to the Meta-analysis, among the 10 interventions, Maxing Shigantang + routine treatment of western medicine demonstrated the most significant effect, and the effect of the interventions was in the following order: Maxing Shigantang + routine treatment of western medicine > routine treatment of western medicine, Shegan Mahuangtang + routine treatment of western medicine> Xiao Qinglongtang + routine treatment of western medicine > Shegan Mahuangtang > Dingchuantang + routine treatment of western medicine. For the cold-induced asthma, the effect of Shegan Mahuangtang + routine treatment of western medicine was remarkable, and for the heat-induced asthma, the corresponding intervention was Dingchuantang + routine treatment of western medicine. Shegan Mahuangtang was outstanding in improving the percentage of forced expiratory volume in the first second in predicted value (FEV1%). ConclusionThe combination of western medicine with the five prescriptions was more effective than the western medicine alone, particularly the combination with Maxing Shigantang. The combination of Shegan Mahuangtang and western medicine was outstanding in the treatment of cold-induced asthma, while the corresponding intervention for heat-induced asthma was the combination of Dingchuantang and western medicine. However, a large number of RCT with scientific design and higher quality are still needed to verify the conclusion.
8.Mechanism of Xiaochuanning Granules in Treatment of Bronchial Asthma via PI3K/Akt Signaling Pathway Based on Network Pharmacology and Experimental Verification
Shuai-yang HUANG ; Dan HOU ; Gui-rui HUANG ; Ming-sheng LYU ; Xue-feng GONG ; Shi-yu ZHANG ; Zhi-jie ZHANG ; Hong-sheng CUI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(9):150-157
ObjectiveTo explore the underlying molecular mechanism of Xiaochuanning granules in the treatment of bronchial asthma based on the network pharmacology and experimental verification through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway on ovalbumin (OVA) sensitization-induced bronchial asthma model in rats. MethodThe main active ingredients and targets of Xiaochuanning Granules were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). The targets related to bronchial asthma were obtained from five disease databases such as GeneCards and Online Mendelian Inheritance in Man (OMIM). The common targets were screened out through the Venn diagram. STRING was used to construct the protein-protein interaction (PPI) network of "compound-disease", and Cytoscape 3.8.0 was used to establish a network of key active ingredients of Xiaochuanning granules and core target genes ("ingredient-gene" network). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed through DAVID. The bronchial asthma model was induced by OVA stimulation in rats. Bronchial and lung tissue inflammation was observed by hematoxylin-eosin (HE) staining, and the enrichment analysis results of the network pharmacology were verified by Western blot. ResultIn this experiment, 232 active ingredients and 4 687 related targets of Xiaochuanning granules were screened out, and 233 common targets of Xiaochuanning granules and bronchial asthma were collected, including eosinophil-derived neurotoxin 1 (EDN1), cyclic AMP response element-binding protein 1 (CREB1), cyclin-dependent kinase inhibitor 1A (CDKN1A), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 14 (MAPK14), and Akt1. KEGG pathway analysis revealed 186 related signaling pathways, indicating that the PI3K/Akt signaling pathway presumedly played a key role in the treatment of bronchial asthma by Xiaochuanning granules. The animal experiment showed that Xiaochuanning granules relieved the airway inflammation and smooth muscle hyperplasia in rats and down-regulated the gene expression of PI3K and Akt as compared with the conditions in the model group (P<0.05). ConclusionXiaochuanning granules have the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of asthma. Xiaochuanning granules may exert anti-inflammatory effects by regulating the expression of genes related to the PI3K/Akt signaling pathway. The present study is expected to provide a theoretical basis for follow-up in-depth research on the complex mechanism of Xiaochuanning granules in the treatment of bronchial asthma.
9.Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/β-catenin Signaling Pathway
Jia-mei WANG ; Xue-feng GONG ; Ming-sheng LYU ; Dan HOU ; Shuai-yang HUANG ; Shi-yu ZHANG ; Hong-sheng CUI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(2):47-54
ObjectiveTo explore the intervention effect of Baofeikang granule (BFK) on the rat model of pulmonary fibrosis through the Wnt/β-catenin signaling pathway. MethodAfter adaptive feeding for one week, 50 healthy rats were randomly divided into a blank group (n=8) and an experimental group (n=42). After anesthesia, the rats in the experimental group were injected with bleomycin sulfate solution (5 mg·kg-1) into the trachea for the induction of the pulmonary fibrosis model. Those in the blank group were injected with the same amount of normal saline under the same manipulation. On the 7th day after modeling, one of the remaining 33 rats alive was randomly removed, and the other 32 model rats were assigned into a model group (n=8), a prednisone acetate (1.17 mg·kg-1) group (n=8), a low-dose BFK (13.59 g·kg-1) group (n=8), and a high-dose BFK (27.18 g·kg-1) group (n=8). The rats in the groups with drug intervention were treated correspondingly by gavage once per day for 21 days, and those in the blank group and the model group received the same amount of normal saline. The pulmonary compliance and ventilatory function, the scores of pathological changes and fibrosis, the levels of type Ⅰ collagen (Col Ⅰ) in lung tissues and hydroxyproline (HYP) in the serum, and the relative expression of Wnt3a and β-catenin protein in lung tissues were compared. ResultCompared with the blank group, the model group showed reduced pulmonary function indexes, such as forced vital capacity (FVC), peak expiratory flow (PEF), the resistance of lung (RL), and dynamic compliance (Cdyn) (P<0.05, P<0.01), severely damaged lung tissue morphology, massive formed continuous fibrous foci, increased fibrosis score (P<0.01), elevated levels of Col Ⅰ in lung tissues and HYP in the serum (P<0.01), and up-regulated expression of Wnt3a and β-catenin (P<0.01). FVC, PEF, and Cdyn levels in the prednisone acetate group and the BFK groups were higher than those in the model group (P<0.05, P<0.01). Pathological changes were improved in the groups with drug intervention, and fibrosis scores were decreased as compared with the model group (P<0.05, P<0.01). The scores in the BFK groups were lower than that in the prednisone acetate group (P<0.01). The levels of Col Ⅰ and HYP in the groups with drug intervention were lower than those in the model group (P<0.05, P<0.01). The level of Col Ⅰ in the prednisone acetate group was higher than that in the high-dose BFK group (P<0.01). The levels of serum HYP in the BFK groups was lower than that in the prednisone acetate group (P<0.01). The protein expression of Wnt3a in lung tissues of the high-dose BFK group was lower than that of the model group (P<0.05). The protein expression of β-catenin in the prednisone acetate group and the BFK groups was lower than that in the model group (P<0.05, P<0.01), and the expression level in the high-dose BFK group was lower than that in the prednisone acetate group (P<0.01). ConclusionBFK can relieve bleomycin sulfate-induced pulmonary fibrosis, reduce collagen deposition, improve pulmonary compliance, and enhance pulmonary ventilatory function in rats. One of its mechanisms is presumedly the inhibition of the Wnt/β-catenin signaling pathway.
10.Effect of electroacupuncture at different time on circadian rhythm and SCN epigenetic modification in mice with hepatocellular carcinoma.
Shuai HOU ; Shen ZHENG ; Jianing WANG ; Xiong CHEN ; Zelan ZHONG ; Hong XUE ; Shasha CHEN
Chinese Acupuncture & Moxibustion 2018;38(8):864-870
OBJECTIVETo observe the effects of electroacupuncture (EA) on the circadian rhythm and suprachiasmatic nucleus (SCN) epigenetic modification in mice with hepatocellular carcinoma (HCC), and to explore the epigenetics mechanism of EA on circadian rhythm in patients with HCC.
METHODSAccording to six zeitbeger time (ZT) of ZT0 (7:00), ZT4 (11:00), ZT8 (15:00), ZT12 (19:00), ZT16 (23:00) and ZT20 (3:00), a total of 108 eligible male C57BL/6J mice were divided into a blank group, a model group and an EA group at each ZT, 6 mice each group. Injection of H22 cancer cell suspension was used to establish the HCC model. After 11 days, EA (2 Hz/15 Hz, 0.2 mA) for 10 days was applied at "Ganshu" (BL 18) and "Zhiyang" (GV 9) in the EA group at each ZT, once a day, 15 min a time; the rats in the blank group and model group were treated with immobilization at the same time and under the same conditions. ClockLab (ACT-500) software was used to record the activity rhythm of mice. After 10 days intervention, MATLAB (R2007b) was used to export the circadian rhythm of mice, and the amplitude and peak phase of the mice were analyzed. The high-throughput epigenetics PCRarray array was applied to detect epigenetics-related gene expression in SCN.
RESULTS(1) After modeling, compared with the blank group, the amplitude of activity was decreased and peak phase was delayed in the model group and EA group at each ZT (all <0.05), but the difference of rhythm parameters between the model group and EA group was not significant (all > 0.05). (2) After intervention, compared with the model group, the amplitude of activity in the EA group at ZT 8 was increased and peak phase was advanced (both <0.05); the difference of the activity amplitude and peak phase between the EA group and model group at ZT0, ZT4, ZT12, ZT16 and ZT20 was not significant (all >0.05); compared with the ZT0, ZT4, ZT12, ZT16 and ZT20, the amplitude of activity in the EA group at ZT 8 was increased and peak phase was advanced (all <0.05). (3) The results of epigenetic PCRarray array showed that after intervention at ZT 8, compared with the blank group, the expression of 48 epigenetic-related genes in SCN of HCC mice was up-regulated; compared with the model group, the relative expression of 49 epigenetic-related genes in the SCN was down-regulated in the EA group; there were 23 epigenetic-related genes differentially expressed among the three groups.
CONCLUSIONEA has benign regulation on circadian rhythm of HCC mice, and achieves the best efficacy at ZT 8. EA at ZT 8 could down-regulate the overexpression of epigenetic-related genes.