1.Novel hybrids of (phenylsulfonyl)furoxan and N-benzyl matrinol as anti-hepatocellular carcinoma agents.
Li-qin HE ; Qi YANG ; Ya-xian WU ; Xiao-shan WANG
Acta Pharmaceutica Sinica 2015;50(5):574-578
N-Benzyl matrinol was obtained by hydrolysis, benzylation and reduction reaction from matrine. A series of hybrids (8a-8n) from (phenylsulfonyl)furoxan and N-benzyl matrinol were synthesized and biologically evaluated as anti-hepatocellular carcinoma agents. All target compounds were evaluated for anti-proliferative activity against human hepatocellular Bel-7402, SMMC-7721, Bel-7404, and HepG2 cells in vitro by MTT method. The results indicated that all of these compounds had potent anti-proliferative activity which were more potent than their parent compound and 5-FU, especially 8a-8h and 8j showed the strongest anti-HCC HepG2 cell activity with IC50 values of 0.12-0.93 μmol x L(-1).
Antineoplastic Agents
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pharmacology
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Carcinoma, Hepatocellular
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Fluorouracil
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Hep G2 Cells
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Humans
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Liver Neoplasms
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Oxadiazoles
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pharmacology
2.The relationship between four GWAS-identified single nucleotide polymorphisms and female breast canc-er in Henan population
Yaning HE ; Qi CHEN ; Hui LIU ; Xianfu SUN ; Chaojun LIU ; Yingbo SHAO ; Ya ZHAO
Chinese Journal of Endocrine Surgery 2015;(5):367-371
Objective To verify the association between common breast cancer susceptibility loci which have been confirmed in European and Asian populations and breast cancer susceptibility in sporadic breast cancer among the Han nationality in Henan province , and to analyze their genotypes in the internal type of breast cancer . Methods In 253 breast cancer patients ( the case group ) and 343 patients who had benign breast lesions ( the control group), rs2046210(6q25.1), rs2981582(EGFR2), rs889312(MAP3K1), and rs3803662(TOX3/TNRC9)were genotyped by SNP im-LDR technique.According to estrogen receptor(ER), progesterone receptor (PR), human epidermal growth factor receptor 2(HER2)and Ki67, breast cancer are divided into 5 types:Lu-minal A, Luminal B, HER2-enrich, Luminal HER2, and triple negative breast cancer ( TNBC).Results rs2046210(6q25.1), rs2981582(EGFR2), rs889312(MAP3K1)had no statistical differences between the case group and the control group(P=0.421, 0.459, and 0.468), but the genotype of rs3803662(TOX3/TNRC9)in the case group and the control group had statistical difference (P=0.037).The allelic frequencies of rs3803662 between the case group and control group were different in codominant inheritance ( OR=2.19, 95%CI:1.19-4.02)and recessive genetic models (OR =2.06,95% CI:1.15 -3.70).Compared with AA and GA, GG in-creased the risk of breast cancer ( P =0.012, 0.015 ).The genotypes of rs2046210 ( 6q25.1 ), rs2981582 (EGFR2), rs889312(MAP3K1), and rs3803662(TOX3/TNRC9)had no difference in different types of breast cancer.Conclusions Four common breast cancer susceptibility loci from GWAS are not entirely associated with breast cancer risk among the Han nationality in Henan province .Only rs3803662(TOX3/TNRC9)is confirmed to increase the risk of breast cancer .Different genotypes of 4 loci distribute equally in different types of breast cancer .
3.Clinical effect of anterior vitrectomy for congenital cataract
Hua, HE ; Feng, ZHOU ; Qi, ZHU ; Qian, WANG ; Xue-Mei, WU ; Jian, MA ; Ya-Yun, WANG
International Eye Science 2015;(5):825-827
?AlM: To evaluate the clinical efficacy of posterior continuous curvilinear capsulorhexis ( PCCC ) combined with anterior vitrectomy in preventing posterior capsule opacification of congenital cataract surgery.
?METHODS:Postoperative clinical follow-up data of 82 cases ( 87 eyes ) with congenital cataract treated in Eye Center of our hospital from January 2011 to August 2014 were retrospectively analyzed. The patients were divided into the surgical control group ( 38 cases, 40 eyes, recieved phacoemulsification + PCCC ) and the study group ( 44 cases, 47 eyes, accepted phacoemulsification+ PCCC + anterior vitrectomy). The incidence of central optic axis opaque and postoperative visual acuity distribution were recorded at 1a follow - up. lntraoperative and postoperative complications were observed.
?RESULTS:The rate of central optic axis opaque grade 0 in control group was 37. 5%, compared to 76. 6% in study groups. The opacity distribution ratio of grade 1,2,3 and 4 in study group were lower than that of control group, and the central optic axis opacity distribution ratio in study group was significantly better than that of control group (P<0. 05). The 19 eyes(47. 5%) of visual acuity testing ≤0. 5 in control group , was higher than the 7 eyes(14. 89%) of that in the study group, The 21 eyes (52. 5%) of visual acuity testing >0. 5 in control group was lower than the 40 eyes ( 85. 11%) of that in study group. The visual acuity between two groups has statistical significance difference after 1a follow-up ( P<0. 05 ) , and the visual acuity in study group was significantly better than that in the control group. The postoperative intraocular pressure at 1mo and 1a follow-up was lower than before operation in two groups ( P<0. 05), but there was no significant difference between two groups in intraocular pressure (P<0. 05).
?CONCLUSlON: Combination of phacoemulsification, PCCC and anterior vitrectomy presents reliable clinical effects on postoperative central optic axis opacity distribution ratio and visual acuity, and it should be adopted to prevent the occurrence of posterior capsule opacification.
4.Research progress of ionizable lipid nanoparticles for siRNA delivery
Ya-nan ZHAO ; Wei HE ; Quan-lin SHAO ; Hua-yu LIU ; Ming-qi LIU ; Ran MO
Acta Pharmaceutica Sinica 2023;58(8):2292-2299
Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.
5.Neurobehavioral function of neonatal mice following excitotoxic brain damage.
Zhi-Ye QI ; Xiang-Ying HE ; Qi LI ; Ya-Xiong MO ; Kun LIANG
Chinese Journal of Contemporary Pediatrics 2009;11(3):191-193
OBJECTIVETo assess the changes of neurobehavioral function in a neonatal mouse model of excitotoxic brain damage.
METHODSFifty-five 5-day-old ICR neonatal mice were randomly assigned to three groups: blank (no intravenous) control (n=20), saline control (n=20) and excitotoxic brain damage model (ibotenic acid treatment, n=15). Behavioral function was evaluated by the surface righting reflex test (postnatal days 6-10), the swimming test (postnatal days 8-12) and the Y-maze discrimination learning test (postnatal days 33-34).
RESULTSRighting time in the surface righting reflex test in the ibotenic acid treatment group on postnatal days 6-10 was more prolonged than that in the two control groups (p<0.05). Swimming test scores in the ibotenic acid treatment group were significantly lower than those in the two control groups (p<0.05). In the Y-maze discrimination learning test, the mice from the ibotenic acid treatment group performed significantly worse than two control groups, presenting with increased learning times (19.79+/-2.42 vs 16.29+/-2.48 or 16.30+/-2.37; p<0.05) and achieving a lower correct percentage (86.7% vs 96.5% or 95.0%) (p<0.05).
CONCLUSIONSThe developmental reflexes and learning and memory functions were impaired in neonatal mice following excitotoxic brain damage. Behavioral testing is useful in the evaluation of early developmental reflexes and long-term neurobehavioral outcome in neonatal mice with excitotoxic brain damage.
Animals ; Animals, Newborn ; Behavior, Animal ; drug effects ; Brain ; drug effects ; Excitatory Amino Acid Agonists ; toxicity ; Female ; Ibotenic Acid ; toxicity ; Male ; Maze Learning ; drug effects ; Mice ; Mice, Inbred ICR ; Swimming
6.Mechanism of PC12 cell differentiation induced by total salvianolic acid
Yang SHEN ; Qi ZHANG ; Jia-Qi ZHAO ; Ya-Juan TIAN ; Qin-Qing LI ; Shi-Feng CHU ; Wen-Bin HE
Chinese Journal of Pharmacology and Toxicology 2018;32(2):99-104
OBJECTIVE To study the differentiation of PC12 cells induced by total salvianolic acid (Tsa) and the mechanism. METHODS MTT assay was used to detect the effect of Tsa 0.01, 0.1 and 1.0 μg·L-1on proliferation of PC12 cells and on the cells damaged by oxygen and glucose deprivation (OGD).The number of projections of PC12 cells was statistically analyzed.Western blotting was applied to detect the levels of microtubule-associated protein2 (MAP-2), extracellular signal-regulated kinase1/2 (ERK1/2), phosphorylated ERK1/2(p-ERK1/2), mitogen-activated protein kinase kinase1/2(MEK1/2) and p-MEK1/2 proteins.MEK inhibitor U0126 was examined for its effect on expressions of p-ERK1/2 and ERK1/2 protein in PC12 cells induced by Tsa 1.0 μg·L-1.RESULTS Compared with normal control group, Tsa 1.0 μg·L-1could promote PC12 cell proliferation, and the survival rate was increased by 90%, but the survival rate of PC12 cells was not affected by Tsa 0.01 or 0.1 μg·L-1. Compared with OGD injured group,PC12 cells injured by OGD could be repaired by Tsa 0.1 or 1.0 μg·L-1,and the survival rate was increased to (47.7±1.8)% and (63.2±13.0)%, respectively (P<0.05, P<0.01). Compared with normal control group,Tsa 0.01,0.1 and 1.0 μg·L-1could promote the growth of PC12 cell projections (P<0.01). Western blotting results showed that Tsa could promote the expressions of MAP-2, p-ERK1/2 and p-MEK1/2 proteins, and this effect could be blocked by U0126 inhibitor (P<0.01). CONCLUSION Tsa can induce the proliferation and differentiation of PC12 cells, the mechanism of which is possibly the activation of p-MEK and p-ERK1/2.
7.Hipbone biomechanical finite element analysis and clinical study after the resection of ischiopubic tumors.
He YA-QI ; Zhang XUE-LIN ; Tang BING-HANG ; Yang ANG
Chinese Medical Sciences Journal 2012;27(3):153-160
OBJECTIVETo investigate the changes of hipbone biomechanics after the resection of ischiopubic tumors and their relationships with the complications in the convalescent stage, and directing the postoperative pelvic reconstruction.
METHODSDICOM data were used to create an intact hipbone finite element model and postoperative model. The biomechanical indices on the same region in the two models under the same boundary condition were compared. The differences of displacement, stress, and strain of the two models were analyzed with statistical methods.
RESULTSThe distribution areas of the hipbone nodes' displacement, stress, and strain were similar before and after the simulated operation. The sacroiliac joint nodes' displacement (P=0.040) and strain (P=0.000), and the acetabular roof nodes' stress (P=0.000) and strain (P=0.005) of two models had significant differences, respectively.But the sacroiliac joint nodes' stress (P=0.076) and the greater sciatic notch nodes' stress (P=0.825) and strain (P=0.506) did not have significant differences.
CONCLUSIONSThe resection of ischiopubic tumors mainly affect the biomechanical states of the homolateral sacroiliac joint and acetabular roof. The complications in the convalescent stage are due to the biomechanical changes of the sacroiliac joint and the acetabular roof and disappearances of the stabilization and connection functions of the pubic symphysis and superior ramus of pubis.
Acetabulum ; physiopathology ; Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Pelvic Bones ; physiopathology ; Pelvic Neoplasms ; physiopathology ; surgery ; Sacroiliac Joint ; physiopathology
8.Mutation Analysis of CIB2 196C>T 272T>C and 297C>G in Patients with Non-syndromic Hearing Impairment
Qi LI ; Jun-Dong HE ; Jin-Li WANG ; Yong-Qin ZHENG ; Rong-Xia ZUO ; Ya-Lian SA
Journal of Kunming Medical University 2018;39(5):7-10
Objective To investigate the gene mutations of calcium-and integrin-binding protein 2 (CIB2) 196C>T, 272T > C and 297C > G carried by students with non-syndromic hearing impairment from special educational schools in Yunnan Province. Methods The experimental group included 337 students with non-syndromic hearing impairment who failed to carry deafness gene with GJB2 (35 del G, 176_191 del 16,235delC, 299_300 del AT), GJB3 (C538T,G547A), mtDNA 12S rRNA (A1555G, C1494T), and SLC26A4 (IVS7_2A>G, A2168G) . The control group consisted with 150 healthy people. Genomic DNA was isolated from peripheral blood with EDTA anti-coagulate. The subject's DNA fragments including CIB2 196C>T, 272T > C and 297C> G were amplified by polymerase chain reaction (PCR), and subsequently analyzed by direct sequencing to identify deafness-associated mutations. Results Both in the experimental group and control group, we failed to find the mutation of CIB2 196C>T, 272T>C and 297C>G in all individuals. Conclusion Mutations in CIB2 gene 196C>T, 272T>C and 297C>G are not a frequent cause of non-syndromic hearing loss among deaf people in Yunnan province. It provided important information for deafness with formulating landscape of gene screening in this region.
9.Multi-slice spiral CT urography in the diagnosis of urinary congenital abnormities
Ya-Qi HE ; Bing-Hang TANG ; Liang-Cai LI ; Ren-Guo WU ; De-Cheng HUANG ; Jian-Xiong LIANG ; Chuan-Le DONG ;
Chinese Journal of Radiology 2001;0(08):-
Objective To evaluate the imaging methods,characteristics,diagnostic value of multi- slice CT urography(MSCTU)in congenital abnormities of urinary system.Methods To collect 33 urinary congenital abnormities cases in three years and to analyses these MSCTU images.All examinations were performed with a multi-slice spiral CT scanner.The patients were intravenously injected with 90 ml of Iohexol 300 with a power injector at the rate of 3 ml/s.Nephrographic-phase images were obtained at 75 s after initiation of the injection of contrast material,the appropriate delay time is according to Kidney's enhancement extent and nephrohydrosis degree.Excretory-phase images were obtained through the abdomen and pelvis from 10 min.to 23 h after initiation of the injection of contrast material without abdominal compression.Excretory-phase images were transferred to the workstation and performed maximun intensity projection(MIP),multiplanar reconstruction(MPR),volume rendering(VR),and virtual cystoscopy (VC).Results The urinary congenital abnormities diagnosed by MSCTU in 33 cases,including 1 ectopic kidney,1 horseshoe kidney,1 renal malrotaion,2 supernumerary kidneys,2 ureteral valves,2 retrocaval ureters,4 congenital megaureters,6 ureteropelvic junction stenosis,9 pelviureteric duplication malformations and 5 bladder diverticula.The displaying rate of ureter was 91%(61/66).The scanning time of excretory-phase was less than 20 seconds in All cases.The average CT value of contrast media in displayed ureter lumens was 520 HU.The postprocessing images had clear,dimensional feature and It was satisfy the diagnosis.Conclusion MSCTU has clear,dimensional feature and has strong ability of displaying total anatomy shape and tiny pathology change of congenital abnormities in the urinary system.It is a very useful method for detecting the congenital abnormities in the urinary system.
10.CT findings of Madelung's disease in the head and neck region
Ren-Guo WU ; Bing-Hang TANG ; Ya-Qi HE ; Liang-Cai LI ; De-Cheng HUANG ; Shi-Jun SUN ; Jun-Fang XIAN ; Zhen-Chang WANG ;
Chinese Journal of Radiology 2001;0(08):-
Objective To investigate the CT findings of Madelung's disease in the head and neck region,and to evaluate the value of CT in demonstrating the Madelung's disease in the head and neck region.Methods CT findings of Madelung's disease in the head and neck region in 7 cases were analyzed retrospectively.All were males,with the age from 36 to 60 years,mean 51 years.All patients were underwent CT native scan,and enhanced CT scan was performed on 3 of them.Results CT images in the neck of all patients showed accumulation of nonencapsulated fat within the subcutaneous tissue and(or) deep to the platysma,and(or)within the spaces between the muscles.The fat deposits were ill-defined and symmetrical.In most cases the fat deposits involved the anterior part of the neck(infrahyoid and suprahyoid),submandibular region,the subcutaneous tissue of the nape and deep to the stenomastoid muscles.Conclusions Madelung's disease in the head and neck region have characteristic CT findings,and CT has great value in qualitative and quantitative diagnosis in Madelung's disease.