1.Therapeutic effect of rosuvastatin on atherosclerosis of apolipoprotein E (ApoE)-knockout mice and its mechanism
Wenxuan LYU ; Wenyao LI ; Sijia FAN ; Shu ZHAO ; Wuhu GUO ; Lijuan CHEN ; Yue DENG
Journal of Jilin University(Medicine Edition) 2016;42(2):240-244
Objective:To explore the influence of rosuvastatin in the lipid levels, atherosclerosis plaque and apoptosis in the plaque of atherosclerotic apolipoprotein E (ApoE)-knockout mouse models, and to clarify the mechanism of rosuvastatin in inhibiting atheromatous plaque and apoptosis in the plaque.Methods:Thirty healthy six-week old male mice were randomly divided into high fat diet group (n=10),rosuvastatin group (n=10)and general diet control group (n=10).The mice in first two groups were fed with high fat diet,and the mice in general diet control group were fed with general diet;4 weeks later the mice in three groups were respectively given 0.9% NaCl solution,rosuvastatin (10 mg·kg·d-1 )and 0.9% NaCl solution by gavage for 8 weeks.And then ELISA was used to detect the serum lipid levels,the area of atherosclerotic plaque was measured by HE staining, and the apoptosis in plaques was detected by TUNEL method;the expression of apoptosis-assoicated gene Bax protein was measured by immunohistochemical staining.Results:Compared with high fat diet group,the levels of total cholesterol (TC)and low density lipoprotein cholesterol (LDL-C)of the mice in rosuvastatin group were significantly decreased (P<0.05 or P<0.01),and the 1evel of high density lipoprotein cholesterol (HDL-C)was significantly increased (P<0.01).The aortic atherosclerotic plaque of the mice in high fat diet group was massive with a great quantity of foam cells, cholesterol crystal, necrotic cells and inflammatory cells in the plaque;the aortic atherosclerotic plaque of the mice in rosuvastatin group was smaller with less foam cells,necrotic cells and inflammatory cells;the aortic atherosclerotic plaque area of the mice in rosuvastatin group was significantly smaller than that in high fat diet group (P<0.01);the apoptotic index in the aortic atherosclerotic plaque of the mice in rosuvastatin group was significantly lower than that in high fat diet group (P<0.01).Compared with high fat diet group,the expression of Bax protein in rosuvastatin group was significantly decreased.Conclusion:Rosuvastatin may inhibit the progression of atherosclerotic plaque and the apoptosis in plaques through mitochondrial pathway.
2.A randomized study of de novo combination therapy lamivudine plus adefovir in HBeAg-positive chronic hepatitis B patients with genotype B/C
Huaie LIU ; Jing YOU ; Hongying CHEN ; Jinghua FAN ; Hua LIU ; Ruyi ZHANG ; Shaofeng RAO ; Sijia MA
The Journal of Practical Medicine 2015;(7):1065-1068
Objective To observe the efficacy of de novo combination therapy lamivudine plus adefovir , lamivudine monotherapy and entecavir monotherapy in HBeAg-positive CHB patients with genotype B/C. Methods A total of 182 treatment-naive CHB patients in line with treatment standards of Chinese CHB prevention and treatment guidelines were randomly assigned to three groups and treated with lamivudine plus adefovir or lamivudine monotherapy or entecavir monotherapy for 48 weeks. Results Patients in three groups presented no difference in baseline levels. After treatment by three therapies , the group of lamivudine plus adefovir showed a higher biochemical response rates (12 week P < 0.01, 24 week P < 0.01, 48 week P < 0.01), HBeAg-serological rates(12 week P < 0.01, 24 week P < 0.05, 48 week P < 0.05) and completely virological response rates (12 week P < 0.05, 24 week P < 0.05, 48 week P < 0.05) than lamivudine group. In terms of biochemical response rates , the group of lamivudine plus adefovir had certain advantages when compared with entecavir group. Conclusion De novo combination therapy lamivudine plus adefovir is a good antiviral strategy for chronic hepatitis B patients with B/C genotype viral infection in China.
3.Influence of Shenhong Tongluo Granules in apoptosis in atherosclerosis plaques of ApoE-/- mice and its mechanisms of anti-atherosclerosis
Wenxuan LYU ; Sijia FAN ; Wenyao LI ; Jingwen YU ; Lijuan CHEN ; Yue DENG
Journal of Jilin University(Medicine Edition) 2016;42(5):882-886
Objective:To explore the influence of Shenhong Tongluo Granules in the lipid levels,atherosclerosis plaques and apoptosis in the plaques of atherosclerotic apolipoprotein E (ApoE)-knokout mice,and to clarify the mechanism of Shenhong Tongluo Granules in anti-atherosclerosis.Methods:Forty SPF male mice aged six-week old were randomly divided into normal control group,model group,low dose of traditional chinese medicine (TCM) group and high dose of TCM group (n=10)after fed adaptively for 1 week.The mice in normal control group were fed with normal diet continuously, the mice in other three groups were fed with high fat diet to establish atherosclerosis model,and then the mice in low and high doses of TCM groups were respectively given Shenhong Tongluo Granules (5.06 and 10.12 g·kg-1 · d-1 )by gavage for 6 weeks. The levels of serum total cholesterol (TC),triglycerides (TG),low density lipoprotein cholesterol (LDL-C)and high density lipoprotein cholesterol (HDL-C)of the mice in various groups were measured after the eyeball blood was collected.The aortic arch tissue was separated,and the morphotogy and the areas of atherosclerotic plaques were observed and calculated by HE staining;the apoptosis in plaques of the mice was evaluated by TUNEL method, and the apoptosis index was calculated. The expressions of apoptosis-assoicated gene Bcl-2 and Bax protein were measured by immunohistochemical staining.Results:The serum level of TG in low dose of TCM group was lower than that in model group (P <0.05);the serum levels of HDL-C in low and high doses of TCM groups were lower than that in model group (P <0.05 or P <0.01);the serum levels of TG and HDL-C in high dose of TCM group was higher than that in low dose of TCM group (P <0.05).The areas of atherosclerotic plaques of the mice in low and high doses of TCM groups were significantly smaller than that in model group (P <0.01).The apoptosis index of mice in low and high doses of TCM groups were significantly lower than that in model group (P <0.01);the expression levels of Bcl-2 protein in atherosclerosis plaques of the mice in low and high doses of TCM groups were lower than that in model group,while the expression levels of Bax were significantly higher than that in model group (P <0.05 or P <0.01).Conclusion:Shenhong Tongluo Granules could effectively reduce the serum lipid level of ApoE-/-mice,meanwhile it could inhibit apoptosis by regulating the expressions of Bcl-2 and Bax protein,and then inhibit the progression of atherosclerotic plaques.
4.Therapeutic effect of massage and electro-acupuncture combined with Yaobi-Zhuyu-Zhitong decoction on lumbar intervertebral disc herniation with qi stagnation and blood stasis type
Sijia FAN ; Chuanyao LIU ; Lanfen HUANG ; Haiwen LIN ; Li XU
International Journal of Traditional Chinese Medicine 2019;41(3):243-247
Objective To explore the efficacy of electroacupuncture and massage combined with Yaobi-Zhuyu-Zhitong decoction in the treatment of lumbar disc herniation (LDH). Methods A total of 100 LDH patients with qi stagnation and blood stasis type who met the inclusion criteria were randomly divided into two groups, 50 in each group. The control group was treated with Yaobi-Zhuyu-Zhitong decoction, and the observation group was treated with electroacupuncture and massage on the basis of the control group. Both groups were treated for 4 weeks. The VAS scale was used to evaluate the degree of pain. The Japanese Orthopedic Association Scores (JOA) was used to evaluate the efficacy of low back pain. The Oswestry dysfunction index was used to evaluate the recovery of lumbar function, and the improvement of daily activities of patients after treatment was evaluated.Results After treatment, the VAS score of the observation group was significantly lower than that of the control group, and the JOA score was significantly higher than that of the control group (t value were 9.870, 8.214, P<0.01). The excellent and good rates of Oswestry dysfunction index before and after treatment in the observation group were 34.0% (17/50) and 86.0% (43/50), respectively, and the control group was 24.0% (12/50) and 44.0%(22/50), respectively. The excellent rate of Oswestry dysfunction index in the two groups was significantly higher than that in the same group before treatment (χ2 values were 28.167, 4.456, P<0.01), and the observation group was significantly higher than the control group (χ2=19.385, P<0.001). The scores of daily activities such as walking, weight-bearing, sitting for a long time, bending over, washing, standing, sleeping and turning over in the observation group were significantly higher than those in the control group (t values were 3.689, 1.661, 3.621, 3.621, 3.300, 1.661, 1.461 respectively, all Ps<0.05). The total effective rate was 94.0% (47/50) and the control group was 76.0% (38/50). The difference between the two groups was statistically significant (χ2=6.353, P=0.012). Conclusions Electroacupuncture and massage combined with Yaobi-Zhuyu-Zhitong decoction can improve the lumbar function, reduce the degree of lumbar pain, improve the quality of life of the LDH patients with qi stagnation and blood stasis type.
5.Risk factors and prognosis of persistent inflammation-immunosuppressive catabolism syndrome in malignant tumor patients with lung infection after chemotherapy
Sijia FAN ; Ni SUN ; Yongfei ZHANG ; Liying ZHANG ; Xiujiang LI ; Guoxing ZHANG
Cancer Research and Clinic 2019;31(3):172-175
Objective To investigate the risk factors and prognosis of persistent inflammation-immunosuppressive catabolism syndrome (PICS) in malignant tumor patients with lung infection after chemotherapy.Methods A total of 128 malignant tumor patients with pulmonary infection after chemotherapy from January 2014 to January 2018 in Jilin Cancer Hospital were collected.According to whether the patients were complicated with PICS,the patients were divided into the PICS group (44 cases) and the control group (84 cases).The clinical characteristics and prognosis of the two groups were compared,and the risk factors of PICS during hospitalization were analyzed.Results The acute physiology and chronic health evaluation (APACHE) Ⅱ score and sequential organ failure assessment (SOFA) score in the PICS group were higher than those in the control group [(18.6±3.8) vs.(15.9±4.0),t =3.598,P < 0.01;(4.8±1.5) vs.(4.0±1.6),t =2.832,P =0.005].When compared with the control group,the proportion of lung cancer in the PICS group was increased [47.7% (21/44) vs.23.8% (20/84),x2 =8.378,P =0.006],and the albumin was decreased [(28.8±3.3) g/L vs.(30.8±2.9) g/L,t =3.695,P < 0.01],the C reactive protein was increased [(60±8) mg/L vs.(45±8) mg/L,t =9.520,P < 0.01],hospital duration was prolonged [(33±7) d vs.(26±7) d,t =4.820,P < 0.01],hospital mortality was increased [22.7% (10/44) vs.4.8% (4/84),x2 =9.567,P =0.002].Multiple factor logistic regression analysis showed that the APACHE Ⅱ score > 20,lung cancer and the albumin < 30 g/L were the risk factors for PICS in the malignant tumor patients with lung infection after chemotherapy (all P < 0.05).Conclusion The incidence of PICS in malignant tumor patients with pulmonary infection after chemotherapy is high,and the risk factors for the poor prognosis include APACHE Ⅱ score >20,lung cancer and the albumin <30 g/L.
6.Progress in the mechanism of estrogen receptors in skeletal muscle diseases
Sijia LI ; Shusheng FAN ; Xiaofei HHUANG ; Chunjie LI ; Zhenzhou JIANG
International Journal of Pediatrics 2021;48(8):555-558
Estrogen receptors are steroid receptors, widely distributed in skeletal muscle, liver and other tissues.Currently, there are 5 known estrogen receptors.Different estrogen receptors are distributed in different places and have different functions.By mediating different estrogen receptors, estrogen plays an important role in anti-inflammation, promoting proliferation and inhibiting muscle atrophy.Skeletal muscle is the main tissue in the human body, accounting for about 40% of body weight.Skeletal muscle not only plays the role of exercise and support, but also plays an important role in maintaining the body′s metabolism.In recent years, estrogen receptors have received extensive attention in skeletal muscle diseases.Estrogen receptors are considered as potential targets for the treatment of skeletal muscle diseases such as Duchenne muscular dystrophy(DMD)and myotubular myopathy(MTM). This article reviews the research progress of estrogen receptors in skeletal muscle diseases.
7.Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology, molecular docking, and in vitro experiments
Shuangqiao Liu ; Xin Liu ; Sijia Jiang ; Min Fu ; Jinxi Hu ; Jiaqi Liu ; Xiaoxu Fan ; Yingtong Feng ; Shujing Zhang ; Jingxia Wang
Journal of Traditional Chinese Medical Sciences 2024;11(1):55-66
Objective:
To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments.
Methods:
Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot.
Results:
Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells.
Conclusion
P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.
8.Functional study on elastase regulation of inflammatory neutrophils recruitment
Yang LIU ; Ling MENG ; Sijia FAN ; Chunguang REN ; Huan ZHANG
Chinese Journal of Immunology 2024;40(3):449-455
Objective:To explore the effect of neutrophil elastase(NE)on neutrophil inflammatory recruitment.Methods:Mice bone marrow-derived neutrophils were pretreated with an exogenous elastase inhibitor-sivelestat sodium.The effects of elastase inhibition on the in vivo inflammatory recruitment,chemotaxis,adhesion,cell polarization and spreading of NE were examined by peritonitis adoptive transfer assay,dunn chamber,flow chamber,immunofluorescence staining and spreading assay,respectively.The effects of elastase inhibition on NE phagocytosis and reactive oxygen species(ROS)release capacity were detected by flow cytom-etry and the luminol chemiluminescence system.Results:Sivelestat sodium pretreatment significantly attenuated neutrophil in vivo in-flammatory recruitment(P<0.001);impaired neutrophil perception of chemotaxis in vitro(P<0.05),slowed chemotactic velocity(P<0.05),and decreased the chemotactic distance(P<0.05);reduced the adhesion of neutrophils to inflamed endothelial cells(P<0.000 1)and inhibited the phagocytosis of bacteria by neutrophils(P<0.01);however,there was no significant effect on neutrophil spreading,polarization and ROS.Conclusion:NE inhibition significantly impaired the inflammatory recruitment cascade response and phagocyto-sis of neutrophils in vitro and in vivo but had no significant effect on the spreading,polarization and ROS release of neutrophils.
9.Concomitant use of immobilized uridine-cytidine kinase and polyphosphate kinase for 5'-cytidine monophosphate production.
Sijia WU ; Jie LI ; Chenlong HU ; Junyu TIAN ; Tong ZHANG ; Ning CHEN ; Xiaoguang FAN
Chinese Journal of Biotechnology 2020;36(5):1002-1011
Uridine-cytidine kinase, an important catalyst in the compensation pathway of nucleotide metabolism, can catalyze the phosphorylation reaction of cytidine to 5'-cytidine monophosphate (CMP), but the reaction needs NTP as the phosphate donor. To increase the production efficiency of CMP, uridine-cytidine kinase gene from Thermus thermophilus HB8 and polyphosphate kinase gene from Rhodobacter sphaeroides were cloned and expressed in Escherichia coli BL21(DE3). Uridine-cytidine kinase was used for the generation of CMP from cytidine and ATP, and polyphosphate kinase was used for the regeneration of ATP. Then, the D403 metal chelate resin was used to adsorb Ni²⁺ to form an immobilized carrier, and the immobilized carrier was specifically combined with the recombinant enzymes to form the immobilized enzymes. Finally, single-factor optimization experiment was carried out to determine the reaction conditions of the immobilized enzyme. At 30 °C and pH 8.0, 60 mmol/L cytidine and 0.5 mmol/L ATP were used as substrates to achieve 5 batches of high-efficiency continuous catalytic reaction, and the average molar yield of CMP reached 91.2%. The above method has the advantages of low reaction cost, high product yield and high enzyme utilization rate, and has good applied value for industrial production.
Cytidine Monophosphate
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metabolism
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Escherichia coli
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genetics
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Industrial Microbiology
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methods
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Phosphotransferases (Phosphate Group Acceptor)
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metabolism
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Uridine Kinase
10.Identification of terpene synthase gene family members in Rhododendron and its relationship with terpenoid metabolism.
Guoxia YANG ; Baoxin JIANG ; Fan HE ; Sijia LÜ ; Dongbin LI ; Yonghong JIA ; Ping ZHU ; Xiaohong XIE ; Yueyan WU
Chinese Journal of Biotechnology 2022;38(10):3740-3756
Terpene synthase (TPS) plays important roles in the synthesis of terpenoids which are the main fragrances in Rhododendron flowers. To understand the function of TPS genes in terpenoid metabolism in relation to flower aroma formation, we identified all TPS gene family members in Rhododendron by analyzing its genome database. We then used a transcriptomic approach to analyze the differential gene expression patterns of TPS gene family members in the scented flower Rhododendron fortunei compared to the non-scented flower Rhododendron 'Nova Zembla'. The contents of terpenoid compounds in petals of the above two Rhododendron species at different developmental stages were also measured by using qRT-PCR and head space-solid phase micro-extraction combined with gas chromatography-mass spectrometry. Our results showed that a total of 47 RsTPS members, with individual lengths ranged from 591 to 2 634 bp, were identified in the Rhododendron genome. The number of exons in RsTPS gene ranged from 3 to 12, while the length of each protein encoded ranged from 196 to 877 amino acids. Members of the RsTPS family are mainly distributed in the chloroplast and cytoplasm. Phylogenetic analysis showed that RsTPS genes can be clustered into 5 subgroups. Seven gene family members can be functionally annotated as TPS gene family since they were temporally and spatially expressed as shown in the transcriptome data. Notably, TPS1, TPS10, TPS12 and TPS13 in Rhododendron fortunei were expressed highly in flower buds reached the peak in the full blossoming. Correlation analysis between gene expression levels and terpenoid content indicates that the expression levels of TPS1, TPS4, TPS9, TPS10, TPS12 and TPS13 were positively correlated with the content of terpenoids in the petals of R. fortunei at all flower developmental stages, suggesting that these six genes might be involved in the aroma formation in R. fortunei.
Rhododendron/metabolism*
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Phylogeny
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Terpenes/metabolism*
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Family
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Gene Expression Regulation, Plant