1.The protective effect of lipoxin A_4 in a rat model of permanent focal cerebral ischemia
Peipei GUO ; Yuanxu JIANG ; Xihong YE ; Yan WU ; You SHANG ; Shiying YUAN ; Shanglong YAO
Chinese Pharmacological Bulletin 2003;0(10):-
Aim To investigate the protective effect of lipoxin A4(LXA4)on ischemic brain injury in a rat model of permanent focal cerebral ischemia.Methods Adult male Sprague-Dawley rats weighing 200~250 g were used and rats were randomly divided into four groups:sham group,ischemia alone group,LXA4 10 ng group and LXA4 100 ng group.Permanent focal cerebral ischemia was induced by improved thread occlusion of right middle cerebral artery.Approximately 10 mm of nylon surgical thread was inserted into the right internal carotid artery in the rats of sham group.After the middle cerebral artery occlusion,the same volume of LXA4(5 ?l)or isotonic Na chloride(5 ?l)was injected respectively into the right lateral ventricle of the rat in 10 minutes.After 24 h of ischemia,the neurological deficit and the infarct volume were assessed by the method of Longa's score and 2,3,5-triphenyltetrazolium chloride(TTC)staining;the levels of malondialdehyde(MDA)and actvities of myeloperoxidase(MPO)in the ischemia cortex were measured by spectrophotometer;the contents of tumor necrosis factor-?(TNF-?)and interleukin-1?(IL-1?)were assayed by ELISA method.The histopathological change was observed after HE staining.Results Treatment with LXA4 10 ng or 100 ng significantly improved functional recovery,reduced relative infarction volume,inhibited MPO activity,decreased MDA,TNF-? and IL-1? levels,and improved histopathological injury.Moreover,the effects of neurological recovery and decreasing TNF-? level in LXA4 100 ng group were better than those in 10 ng group.Conclusion Treatment with LXA4 protects against permanent focal cerebral ischemia injury in rats.
2.Bioinformatic analysis of small RNA expression during chondrogenesis in rats
Shibin SHAO ; Zixin MIN ; Yuanxu GUO ; Quancheng WANG ; Mengyao SUN ; Yan HAN ; Jian SUN
Journal of Xi'an Jiaotong University(Medical Sciences) 2015;(4):462-466
Objective To study the profiles and function of small RNA (sRNA)gene during chondrogenesis in rats so as to clarify the mechanisms of chondrocytes proliferation and differentiation.Methods All the sRNAs were identified from the female SD rats femoral head cartilages at three time points:at birth,ablactation and maturation,and three sRNA libraries were constructed.The Solexa sequencing and the bioinformatics analysis were employed to be blasted with the genomes of SD rats.Results The perfect match reads in the three libraries were screened out,which were correspondent to the 21 7 921 (41.23%),1 96 650 (38.74%)and 245 436 (41.54%)unique sRNA sequence,respectively.The percentages of 20-24 nt sRNA were 71.94% (d0),72.85% (d21),and 86.39%(d42).Half of clean sequences were 22 nt sRNA.The distribution characteristics of the reads were in line with the high-quality sRNA.More than 62% clean reads were from mature miRNA while the ratios in the three libraries were only 0.69%,0.78% and 0.63%.About 60% of the unique sRNA could not be matched with miRBase20.0 or Rfam9.1.Conclusion The distribution model of miRNA in the three libraries indicates that the miRNAs with different functions or from different sources are involved in the regulation of chondrocytes proliferation and differentiation in bone development and formation.
3.Research advances on the pathogenesis of acute pancreatitis
Zhi ZHENG ; Yuanxu QU ; Yixuan DING ; Wentong MEI ; Yuchen JIA ; Yulin GUO ; Feng CAO ; Fei LI
Chinese Journal of Hepatobiliary Surgery 2021;27(2):152-155
Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Its pathogenesis is not only related to abnormal activation of trypsinogen, but also related to calcium overload, mitochondrial dysfunction, impaired autophagy and endoplasmic reticulum stress. However, the mechanism has not been fully elucidated and needs to be further studied. Currently, there is no effective treatment for AP. It is difficult to prevent the loss of pancreatic function. An in-depth understanding of the pathophysiological mechanisms of AP may help to identify the potential therapeutic targets. Therefore, the purpose of this study is to review recent advances in the mechanism of AP in order to provide more research direction for treatment.
4.Research progress of Kruppel-like factor family in malignant tumors
Zhi ZHENG ; Yixuan DING ; Wentong MEI ; Yulin GUO ; Yuanxu QU ; Jiongdi LU ; Shuang LIU ; Haichen SUN ; Feng CAO ; Fei LI
International Journal of Surgery 2021;48(4):264-268
Malignant tumors usually have no obvious clinical symptoms in the early stage. Most patients are already in the advanced stage when they are diagnosed. Some patients have lost the opportunity for operation, resulting in poor prognosis. Therefore, how to find the best therapeutic target for such patients and improve the prognosis of patients has gradually become the focus of scholar′s attention. Recently, Kruppel-like factor (KLF) is a transcriptional regulator that can bind to the target DNA, and its family plays an important role in the occurrence and development of malignant tumors. It has also been confirmed that the KLF family affects the proliferation, differentiation and migration of tumor cells, but the specific mechanism is still not fully elucidate. Consequently, in order to further explored the effect of the KLF family on tumors, this study intends to briefly review the roles and regulatory mechanisms of the KLF family in the cell proliferation, differentiation and migration of malignant tumors, hoping to provide new target for the biological treatment of tumors.
5.Influence of infection complications on the prognosis of patients with severe acute pancreatitis
Jiongdi LU ; Yixuan DING ; Zhi ZHENG ; Yuanxu QU ; Wentong MEI ; Yulin GUO ; Feng CAO ; Fei LI
International Journal of Surgery 2022;49(10):699-707,C5
Objective:To analyze the effects of infectious complications [infected pancreatic necrosis (IPN) and extra-pancreatic infection (EPI)] on the outcomes of patients with severe acute pancreatitis (SAP), and evaluate the differences in infection time, infection site and infecting species between SAP patients with infections complications.Methods:The clinical data of 66 SAP patients with combined infectious complications admitted to Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were retrospectively analyzed, and SAP patients were divided into IPN group ( n=7), EPI group ( n=14) and co-infection (EPI+ IPN) group ( n=45) according to the type of infection. Whether the study data conformed to a normal distribution was assessed by the Shapiro-Wilk test, normally distributed measures were expressed as mean ± standard deviation ( ± s), and ANOVA was used for comparison between groups; skewed measures were expressed as median (interquartile range) [ M ( Q1, Q3)], and the rank-sum test was used for comparison between groups. Bonferroni correction was used for multiple group comparisons ( P value significance level reduced to 0.017). Quantitative data were compared between groups using the χ2 test or Fisher's exact probability method. Results:There were no statistical differences between the three groups in terms of baseline data at admission (gender, age, etiology, modified CTSI score, degree of pancreatic necrosis, and number of organ failure) ( P>0.05), patients in the EPI group were referred earlier than the other two groups ( P<0.05). In clinical treatment, patients in the IPN group and co-infection group required multiple minimally invasive interventions compared with those in the EPI group ( P<0.05), and the number of patients requiring combined nutritional support, length of intensive care unit stay, and total length of hospital stay were higher in the co-infection group than in the other two groups ( P<0.05). In addition, 360 strains of pathogenic bacteria were cultured in this study, with Gram-negative bacteria being the most common, and patients with SAP were more likely to have EPI in the early stage of disease onset, with bacteremia and respiratory tract infections in the early stage (≤14 d), and bacteremia, urinary tract infections, and catheter-associated infections in the late stage (>14 d). Conclusions:Among patients with SAP, patients in the co-infection group had higher surgical intervention, nutritional support and length of hospital stay than those in the single infection group. It is advisable to prioritize EPI in SAP patients with suspected infections, and the common infectious strains in SAP patients are still predominantly Gram-negative bacteria, and clinicians need to adjust the treatment plan in a timely manner according to the changes in patients′ conditions.
6.Design,synthesis,and evaluation of fluoroquinolone derivatives as microRNA-21 small-molecule inhibitors
Hei YUAN-YUAN ; Wang SI ; Xi XIAO-XIAO ; Wang HAI-PENG ; Guo YUANXU ; Xin MINHANG ; Jiang CONGSHAN ; Lu SHEMIN ; Zhang SAN-QI
Journal of Pharmaceutical Analysis 2022;12(4):653-663
MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone de-rivatives Al-A43 were synthesized and used as miRNA-21 inhibitors.Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells.Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes,including programmed cell death protein 4(PDCD4)and phos-phatase and tensin homology deleted on chromosome ten(PTEN),at 10 uM in HeLa cells.The Cell Counting Kit-8 assay(CCK-8)was used to evaluate the antiproliferative activity of A36;the results showed that the IC50 value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM.Meanwhile,A36 did not display cytotoxicity in BEAS-2B cells(lung epithelial cells from a healthy human donor).Furthermore,A36 significantly induced apoptosis,arrested cells at the G0/G1 phase,and inhibited cell-colony formation in HeLa cells.In addition,mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells,while the expression of miRNA-21 target gene dual-specificity phosphatase 5(DUSP5)was significantly upregulated at both the mRNA and protein levels.Collectively,these findings demonstrated that A36 is a novel miRNA-21 inhibitor.