1.Identification of Atrial Fibrillation-related Inflammatory Genes and Their Association with Immune Cell Infiltration Based on Comprehensive Bioinformatic Analysis
Man YANG ; Xingan ZHAO ; Yunna GE ; Juan QIN ; Xiya WANG ; Siming TAO
Journal of Kunming Medical University 2024;45(3):18-29
Objective To identify inflammation-related genes in atrial fibrillation(AF)and explore the possible role and mechanism of these genes and infiltrating immune cells in the development of AF.Methods A series of bioinformatics analysis combined with machine learning algorithms to identify biomarkers of AF,the receiver operating characteristic(ROC)curves were used to verify the prediction and diagnostic value of key genes,and Spearman correlation analysis was used to clarify the correlation between key genes and infiltrating immune cells.Results 593 differential genes(| log2(fold change,FC)|>1,P<0.05),7 immune cell subtypes(P<0.05)were selected,190 immune-related differential genes were obtained,3 biomarkers(IGF1,PTGS 2 and PPARG),and the correlation analysis showed that 3 markers were significantly associated with infiltrating immune cells(P<0.05).Conclusion IGF1,PTGS2 and PPARG are inflammation-related genes of AF,which are speculated to be closely related to the process and pathway of immune cell infiltration.
2.Regulatory effect of retinoid X receptor on oxidative stress response in-duced by hypoxia/reoxygenation in rat type Ⅱ alveolar epithelial cells
Xiaoting WANG ; Junpeng XU ; Man HUANG ; Sian CHEN ; Qihao ZHANG ; Wenjie CAO ; Yunna TIAN ; Hui GAO ; Wantie WANG
Chinese Journal of Pathophysiology 2024;40(1):89-94
AIM:To investigate the regulatory role of retinoid X receptor(RXR)in oxidative stress response of rat type Ⅱ alveolar epithelial cells(AECII)induced by hypoxia/reoxygenation(HR).METHODS:The AECII were di-vided into control(C)group,HR group,HR+solvent dimethyl sulfoxide(DMSO)group(HD group),HR+RXR agonist 9-cis-retinoic acid(9-RA)group(RA group),and HR+RXR antagonist HX531 group(HX group).Cell Counting Kit-8(CCK-8)method was used to measure the cell viability.Immunofluorescence staining was used to detect the expression of surfactant protein A(SP-A)and RXRα in AECII.Kits were detected to the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in cells.Transmission electron microscopy was used to observe the ultrastructural changes of the cells.Western blot was used to detect the protein level of nuclear factor E2-related factor 2(Nrf2).RT-PCR was used to detect the expression level of Nrf2 mRNA.RESULTS:Compared with C group,the cell viability and SOD activity in HR,HD,RA and HX groups were decreased significantly(P<0.05),the MDA content were increased significantly(P<0.05),the Nrf2 mRNA and protein expression levels were decreased significantly(P<0.05 or P<0.01),and the immuno-fluorescence expression of RXRα was significantly increased(P<0.01).Compared with HR and HX groups,the cells in RA group showed significantly increased cell viability(P<0.05),increased SOD activity(P<0.05),decreased MDA con-tent(P<0.05),increased Nrf2 mRNA and protein expression levels(P<0.01),and significantly increased immunofluo-rescence expression of RXRα(P<0.01).CONCLUSION:Hypoxia/reoxygenation can aggravate the oxidative stress re-sponse of rat AECII,and RXR agonist intervention can alleviate HR-induced rat AECII injury by inhibiting oxidative stress.
3.Effects of sodium hydrosulfide on HK2-NLRP3-GSDMD pathway and pyroptosis induced by lung ischemia/reperfusion in rats
Lu SHI ; Xiaoting WANG ; Zhenzhen LUO ; Jun CHENG ; Sian CHEN ; Jun-Peng XU ; Qihao ZHANG ; Wenjie CAO ; Man HUANG ; Yunna TIAN ; Xuguang JIA ; Wantie WANG
Chinese Journal of Pathophysiology 2024;40(6):1105-1113
AIM:To investigate the effects of sodium hydrosulfide(NaHS)on hexokinase 2(HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3(NLRP3)-gasdermin D(GSDMD)pathway and pyroptosis in-duced by lung ischemia/reperfusion(I/R)in rats.METHODS:Male Sprague-Dawley rats were divided into 6 groups:control group,control+NaHS group,I/R group,low-dose NaHS+I/R(L+I/R)group,medium-dose NaHS+I/R(M+I/R)group,and high-dose NaHS+I/R(H+I/R)group,with 6 rats in each group.The NaHS was administered via intraperi-toneal injection at 1.5 mL,30 min before modeling.The left lung tissues were collected 30 min after ischemia and 1 h af-ter reperfusion,and the wet/dry weight ratio and total lung water content were recorded.Hematoxylin-eosin(HE)staining was used to examine lung tissue morphological changes.The levels of malondialdehyde(MDA),myeloperoxidase(MPO)and lactate in lung tissues were measured with test kits.ELISA was employed to determine the levels of interleukin-1β(IL-1β)and IL-18.The expression of glycolysis-and pyroptosis-related indicators was analyzed by Western blot,qRT-PCR and immunofluorescence staining.RESULTS:Compared with control group,the rats in NaHS group showed no signifi-cant differences in all laboratory tests(P>0.05).The rats in I/R group exhibited significant lung injury,oxidative stress,increased lactate level,and up-regulated glycolysis and pyroptosis(P<0.05 or P<0.01).Compared with I/R group,the indicators in L+I/R group showed a downward trend(P<0.01)or no difference(P>0.05),while those in M+I/R group dis-played a significant reduction(P<0.05 or P<0.01).However,the indexes in H+I/R group exhibited no significant dif-ferences in these tests(all P>0.05).CONCLUSION:A moderate dose(56 μmol·L-1·kg-1)of NaHS mitigated the oc-currence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway,thus contributing to the attenuation of lung I/R in-jury in rats.
4.Effect of metformin preconditioning on AMPK/PINK1 signaling pathway during myocardial ischemia-reperfusion injury in diabetic rats
Yunna MA ; Feng HE ; Fuyu WANG ; Hanmin XIANG ; Huimin ZHOU ; Jianjuan KE ; Yanlin WANG
Chinese Journal of Anesthesiology 2023;43(5):613-617
Objective:To evaluate the effect of metformin preconditioning on adenosine monophosphate-activated protein kinase(AMPK)/PTEN-induced putative protein kinase(PINK1) signaling pathway during ischemia-reperfusion (I/R) injury in diabetic rats.Methods:Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 6 weeks, weighing 120-160 g, were divided into 3 groups ( n=12 each) by the random number table method: diabetic sham operation group (DS group), diabetic myocardial I/R group (DI/R group) and diabetic myocardial I/R+ metformin preconditioning group(DI/R+ Met group). After 4 weeks of feeding a high-fat and high-glucose diet, the model of type 2 diabetes mellitus was induced by a single intraperitoneal injection of 1% streptozotocin 40 mg/kg. The myocardial I/R injury was induced by blocking the anterior descending branch of the left coronary artery for 30 min followed by 120-min reperfusion in anesthetized animals. In DI/R+ Met group, metformin 200 mg/kg was given by intragastric gavage once a day within 1 week before myocardial ischemia. Blood samples from the femoral vein were collected at 120 min of reperfusion for determination of the serum creatine kinase isoenzymes (CK-MB) and cardiac troponin I (cTnI) concentrations by enzyme-linked immunosorbent assay. Then the rats were sacrificed and myocardial tissues were obtained for examination of the pathological changes(by HE staining) and for determination of the percentage of myocardial infarct size (by the double staining of Ewan blue and TTC) and expression of myocardial autophagy-related protein Beclin-1, PTEN-induced putative kinase 1 (PINK1), phosphorylated 5′-adenosine monophosphate-activating protein kinase (p-AMPK), and ratio of microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ (LC3Ⅱ/Ⅰ) (by Western blot). Results:Compared with DS group, the percentage of myocardial infarct size and serum CK-MB and cTnI concentrations were significantly increased, the expression of Beclin-1, p-AMPK and PINK1 in myocardial tissues was up-regulated, the ratio of LC3II/I was increased( P<0.05), and the pathological changes were aggravated in DI/R group and DI/R+ Met group. Compared with DI/R group, the percentage of myocardial infarct size and serum CK-MB and cTnI concentrations were significantly decreased, the expression of Beclin-1, p-AMPK and PINK1 in myocardial tissues was up-regulated, the ratio of LC3Ⅱ/Ⅰ was increased ( P<0.05), and the pathological changes were significantly reduced in DI/R+ Met group. Conclusions:The mechanism by which metformin preconditioning reduces myocardial I/R injury is related to activation of AMPK/PINK1 signaling pathway and up-regulation of mitochondrial autophagy in diabetic rats.
5.Carbon dots derived from Poria cocos polysaccharide as an effective"on-off"fluorescence sensor for chromium(Ⅵ)detection
Qianqian HUANG ; Qianqian BAO ; Chengyuan WU ; Mengru HU ; Yunna CHEN ; Lei WANG ; Weidong CHEN
Journal of Pharmaceutical Analysis 2022;12(1):104-112
Chromium is a harmful contaminant showing mutagenicity and carcinogenicity.Therefore,detection of chromium requires the development of low-cost and high-sensitivity sensors.Herein,blue-fluorescent carbon quantum dots were synthesized by one-step hydrothermal method from alkali-soluble Poria cocos polysaccharide,which is green source,cheap and easy to obtain,and has no pharmacological ac-tivity due to low water solubility.These carbon quantum dots exhibit good fluorescence stability,water solubility,anti-interference and low cytotoxicity,and can be specifically combined with the detection of Cr(Ⅵ)to form a non-fluorescent complex that causes fluorescence quenching,so they can be used as a label-free nanosensor.High-sensitivity detection of Cr(Ⅵ)was achieved through internal filtering and static quenching effects.The fluorescence quenching degree of carbon dots fluorescent probe showed a good linear relationship with Cr(Ⅵ)concentration in the range of 1-100 μM.The linear equation was F0/F=0.9942+0.01472[Cr(Ⅵ)](R2=0.9922),and the detection limit can be as low as 0.25 μM(S/N=3),which has been successfully applied to Cr(Ⅵ)detection in actual water samples herein.
6.Stereoselective pharmacokinetics of itraconazole enantiomers in rats
Yunna ZANG ; Jianguo SUN ; Jiye A ; Yuqing Jiye ; Xiaoliang JIN ; Guangji WANG
Journal of China Pharmaceutical University 2015;46(3):339-344
To investigate the stereoselective pharmacokinetics of itraconazole enantiomers in rats, four cis-ITR stereoisomers at the dose of 15 mg/kg were administered orally to rats. Blood was collected and single stereoisomer of ITZ and hydroxy-itraconazole(OH-ITZ)were determinated simultaneously by LC-MS/MS. Samples were extracted by protein precipitation with acetonitrile. Durashell HILIC column(100 mm×2. 1 mm, 5. 0 m)was used as the analytical column, while a mixture of solvent A(0. 02% acetic acid and 5 mmol/L ammonium acetate in water)and B(50% acetonitrile and 50% methyl alcohol)was used as the mobile phase. A 5. 5 min binary gradient elution(delivered at 0. 5 mL/min)was performed for the separation. LC-MS/MS was performed in positive ion mode with multiple reactions monitoring(MRM). The pharmacokinetic parameters of itraconazole enantiomers after the administration were estimated as follows: the plasma levels and AUC0-∞ of OH-(2S, 4R, 2R)-ITZ and OH-(2S, 4R, 2S)-ITZ were higher than those of OH-(2R, 4S, 2R)-ITZ and OH-(2R, 4S, 2S)-ITZ(P< 0. 001). At the same time, female rats exhibited greater cmax, t1/2, AUC0-∞ than male rats, and the absorption of male rats was more rapid than those of females. The findings indicate significant stereoselective differences in the pharmacokinetic parameters of itraconazole enantiomers and gender difference in rats.
7.Study on correlation between depth of sedation and Narcotrend index in Midazolam target-controlled infusion
Ruiyu LI ; Yunna QU ; Lixun WANG ; Hui LI ; Qitao HE
Chinese Journal of Primary Medicine and Pharmacy 2013;20(15):2252-2254
Objective To investigate the reliability of Narcotrend for monitoring the depth of sedation [the observer's assessment of alterness/sedation(OAA/S) scale] with midazolam and correlation between the depth of sedation and Narcotrend index.Methods 0 ASA Ⅰ-Ⅱ status patients scheduled for elective lower limb operations underwent spinal anesthesia,who were given target-controlled infusion of midazolam.Target plasma concentration was 50ng/ ml at first and increased by 10 ng/ml each grade until OAA/S scale became 1 point.Each target concentration infusion was maintained for 5min.Observe the patient the OAA/S scale to be 5 points.If the operation was not over yet,regulated the appropriate depth of sedation until the end of operation.The Narcotrend index of different OAA/S scale and heart rate,mean arterial pressure,respiration were recorded.Results In the deepening or recovery phase of sedation,OAA/S scales were correlated with Narcotrend index (Spearman' s r =0.786,0.652,all P < 0.05).Conclusion Narcotrend is a good index to guide target controlled infusion of midazolam,the index is closely related with the depth of sedation of midazolam.
8.Establishment of a three-dimensional finite element model of transmission straight wire appliance
Rui DING ; Yunna MAN ; Peiling WU ; Wei WANG
Chinese Journal of Tissue Engineering Research 2013;(33):5942-5948
BACKGROUND:With the development of modern orthodontics, to invent an efficient appliance is the focus in
recent studies. Transmission straight wire appliance was born on this background. This appliance can accelerate occlusion and shorten treatment duration. The relationship between distal width and angulation of gable bends of main arch wire needs to study in depth.
OBJECTIVE:To establish three-dimensional finite element model of transmission straight wire appliance with better biological and mechanical similarity, and to obtain the relationship between distal width and angulation of gable bend of main arch wire.
METHODS:By using scanning of spiral CT with 64 rows, the sectional image data in DICOM format of maxil ary dentition and maxil ae of the volunteers (Class Ⅱ, division 1) were obtained. With the help of Ansys workbench 13.0, Mimics 10.01, Unigraphics NX and Geomagic Studio 8.0 softwares, the three-dimensional finite element model including transmission straight wire appliance, bend, Australian Orthodontic Wire, maxil ae, maxil ary tooth and periodontal ligament was established in Windows XP Service Pack 3 system.
RESULTS AND CONCLUSION:A three-dimensional finite element model of transmission straight wire appliance was established, which consisted of 250 929 elements and 657 766 nodes. Furthermore, three-dimensional finite element model had higher geometric similarity and mechanical similarity, as wel as the advantages of adding or subtracting components according to the requirement of the research. The model was conductive to analyze the mechanical system of transmission straight wire appliance and guide the clinical application and appliance modification.
9.Effect of polypeptide extract from scorpion venom (PESV) on expression of HIF-1alpha and SDF-1/CXCR4 in repopulating H22 tumour tissue during chemotherapy treatment.
Zhaopeng WANG ; Weidong ZHANG ; Licun WU ; Qing JIA ; Zhaoxia WANG ; Yueying ZHANG ; Yunna NING
China Journal of Chinese Materia Medica 2011;36(13):1803-1807
OBJECTIVETo study the expression of HIF-1alpha and SDF-1/CXCR4 in repopulating H22 tumor tissue and the mechanism of angiogenesis of polypeptide extract from scorpion venom (PESV) during chemotherapy treatment.
METHODThe expression of HIF-1alpha and SDF-1/CXCR4 in H22 tumor tissue was monitored by immunohistochemistry, and the expression level was determined by Qwin V3 image analyzing software. The correlation between HIF-1alpha and SDF-1 was analyzed. SDF-1 content was detected by ELISA.
RESULTHIF-1alpha expression was found no difference in model group between 14 d and 21 d, and up-regulated in 28 d. There was no change of HIF-1alpha expression was observed in low-dose PESV group. In high-dose PESV group, the level of HIF-1alpha expression was high in 14 d and low in 21 d. ELISA detecting showed SDF-1 content increased slowly from 14 d to 21 d, highly from 21 d to 28 d. But in high-dose PESV groups, the content increased slowly all the time. The immunohitochemistry method got the same result with ELISA. Correlation analysis showed r = 0.805. CXCR4 expression down-regulated in two PESV treated groups, and no difference was found between these two groups.
CONCLUSIONHIF-1alpha and SDF-1 participated in VEGF expression and angiogenesis in tumor tissue during chemotherapy, while PESV could inhibit the expression of HIF-1alpha and SDF-I.
Animals ; Cell Line, Tumor ; Chemokine CXCL12 ; drug effects ; metabolism ; Down-Regulation ; drug effects ; Hypoxia-Inducible Factor 1, alpha Subunit ; drug effects ; metabolism ; Mice ; Peptides ; pharmacology ; Receptors, CXCR4 ; drug effects ; metabolism ; Scorpion Venoms ; chemistry ; pharmacology ; Scorpions ; chemistry ; Time Factors
10.Application of tissue engineering techniques and materials in prevention and treatment of tendon adhesion induced by movement injury
Xiangdong WANG ; Huiqing MA ; Yunna ZHAO ; Baojuan MA ; Ronghua LIU
Chinese Journal of Tissue Engineering Research 2009;13(51):10157-10160
BACKGROUND:Previous studies have confirmed that healing of in vivo tendon is the outcome of interaction between endogenous healing and exogenous healing. Exogenous healing is a main reason for tendon adhesion, and affects the recovery of tendon function.OBJECTIVE: To explore application of tissue engineering technique and its materials in prevention and treatment of tendon adhesion induced by movement injury.METHODS: Using the key words of "movement injury, biomaterial, tissue engineering, tendon adhesion", we retrieved randomized animal controlled studies and clinical application literatures addressing tendon biomechanics function, adsorbable biomaterial polyglycolic acid, tendon cells-constructed tissue engineered tendon in vitro, biomembrane, chitosan, adsorbable antistick membrane, sodium hyaluronate, bioprotein gel and so on in prevention of tendon adhesion in Chinese Journal Full-text Database published from January 1990 to December 2000. By aggregate analysis of literature data, follow-up and function evaluation, this article summarized clinical application of tissue engineered techniques and materials in prevention of tendon adhesion.RESULTS AND CONCLUSION: A total of 61 literatures were primarily obtained. Following reading titles and abstracts, 31 literatures of irrelevant objectives and contents, and 9 literatures of repetitive contents were excluded. Totally 21 literatures were included for analysis. Tendon adhesion refers to hyperplasia and invasion of surrounding tissues during repair of tendon damage. With the deep understanding of tendon repair healing, application of tissue engineering to preventing tendon adhesion became more and more. Tendon healing is an interaction between endogenous healing and exogenous healing, and mainly endogenous healing, which was simultaneously associated with tendon sheath, vincula tendinum and synovial fluid. Tendon adhesion is mainly induced by excessive action of exogenous healing and damage to surrounding tissues. Tissue engineering is a novel technique. Novel biomaterials are widely used in tissue engineering performance to solve problems such as tendon injury andchondronecrosis. Presently, it Is important to reconstruct tissues, which can reach clinical outcomes of preventing adhesion.

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