1.The role and mechanisms ofω-3 polyunsaturated fatty acids in inducing cell apoptosis and anti-prolif-eration in multiple myeloma
Yu ZHAO ; Xiaoting ZHU ; Yinan WANG
Practical Oncology Journal 2016;30(6):516-522
Objective To explore the role and mechanisms of ω-3 polyunsaturated fatty acids (ω-3PUFA) alone or in combination with dexamethasone ( DEX) in inducing cell apoptosis and anti -proliferation in multiple myeloma(MM).Methods DEX resistance MM cell line MM1R were treated with different concentra-tions of Eicosapentaenoic acid(EPA)or Docosahexaenoic acid(DHA)alone or in combination with DEX for 24hrs or 48hrs.Cell proliferation was detected by MTT .Cell cycle and apoptosis were measured by flow cytometry .The levels of apoptosis related proteins were analyzed by Western blot .Results The proliferation of MM1R was in-hibited by different concentrations (10,20,50,100μM)of EPA or DHA alone or in combination with 10μM DEX in a dose-and time-dependent manner .Inhibition effect was significantly higher in combinative groups than in single agent groups(P<0.05).The percentage of G0/G1 phase and cell apoptosis rate in MM1R treated with dif-ferent concentrations of EPA or DHA alone was increased in a dose -dependent manner ,and being significantly higher in combinative groups than in single agent groups (P<0.05).The expressive levels of cleaved caspase -3 and Bax were up-regulated ,while pro-caspase-3 and BCL-2 were down-regulated in a dose-dependent manner.Conclusion ω-3PUFA can inhibit DEX resistant MM cell proliferation ,arrest cell cycle and induce cell apoptosis ,and has a synergistic anti -resistant effect in combination with DEX ,may serve as a new ,effective MM drugs.
2.Association study between simple febrile seizures and gabbr1 gene and gabbr2 gene
Yujie LI ; Yinan MA ; Yu QI ; Junyi WANG ; Liping ZOU
Chinese Journal of Applied Clinical Pediatrics 2014;29(12):891-894
Objective To investigate whether the gamma-aminobutyric acid (GABAB) receptor genes,including gabbr1 gene and gabbr2 gene,are the susceptible genes for simple febrile seizures (sFS) by screening mutation of gabbr1 gene and gabbr2 gene and to study the possible association between sFS and the 2 genes.Methods All exons and flanking introns of gabbr1 gene and gabbr2 gene were amplified with polymerase chain reaction (PCR) and sequenced to screen the possible mutation on 60 children with sFS in the northern China in Han nationality population.One hundred and one healthy children from the same area were selected as controls,and the genotypes of single nucleotiole polymorphisms (SNPS) (rs29220,rs29230,rs29267 on gabbr1 gene and rs1000440,rs3205936,rs2304391 on gabbr2 gene) were typed by PCR-restriction fragment length polymorphism.EH1.20 software was used to estimate haplotype frequency to study the association with the haplotype as genetic marker between case group and control group.Results No mutation associated with sFS was found in the 60 sFS cases.In all sequenced regions,23 SNPs were identified in both genes:6 SNPs in gabbr1 gene and 17 SNPs in gabbr2 gene.The frequencies of the 6 SNPs were complied well with the Hardy-weinberg equilibrium in sFS group and normal group.Genotype proportions and allele frequencies of 6 SNPs were not significantly different between both groups.The haplotypes of 3 SNPs in gabbr1 gene and in gabbr2 gene distributions were not significantly different between 2 groups.Conclusions No mutations and associations were identified between sFS with both GABAB receptor genes(gabbr1 gene and gabbr2 gene).They may not be the susceptibility gene for simple febrile seizures in Han nationality population in northern China.
3.Research on relative factors of abnormal glycometabolism in chronic hepatitis C patients
Mei LIU ; Feng ZANG ; Yinan YAO ; Peng HUANG ; Rongbin YU
Chinese Journal of Disease Control & Prevention 2017;21(9):909-912,970
Objective Hepatitis C virus patients are often accompanied by insulin resistance and diabetes.To probe the relative factors of abnormal glycometabolism in chronic HCV infections.Methods A total of 1 039 treatment-naive patients that were confirmed chronic HCV infected were enrolled in the study.The demographics,biochemical index parameters and other data about liver function and HCV viral load were got from infectious disease department of Jurong Pepole's Hospital in China.Results A total of 140 (13.5%) patients were diagnosed with some forms of abnormal glycometabolism.The body mass index (BMI) (x2 =9.231,P =0.010),waist circumference (x2 =7.984,P =0.018),systolic blood pressure (x2 =16.366,P <0.001),diastolic blood pressure (x2 =13.970,P =0.001),alanine aminotransferase(ALT) (x2 =4.809,P =0.028),HCV-RNA viral load (t =-3.818,P <0.001) were significantly different between non-diabetic HCV patients and abnormal glycometabolism patients.Multivariate logistic regression analysis showed that ALT(OR =2.986,95% CI:1.171-7.615) and HCV-RNA viral load (OR =2.061,95% CI:1.165-3.644) were found as risk factors in multivariate regression analysis for patients with chronic hepatitis C who had abnormal glucose metabolism.Conclusions Chronic hepatitis C patients with higher ALT and HCV-RNA level were more probably to suffer from abnormal glycometabolism.In order to find potentially novel risk factors of HCV with abnormal glucose metabolisn,further studies about genetic and other clinical factors need to be processed.
4.Effects of Tuina on cartilage degradation and chondrocyte terminal differentiation in rats with knee osteoarthritis (KOA) via the Wnt/β-catenin signaling pathway
Yinan YU ; Youhong XIE ; Chenglin TANG ; Xiao GUO
Journal of Acupuncture and Tuina Science 2023;21(1):18-26
Objective: To investigate the therapeutic effects of Tuina (Chinese therapeutic massage) in a knee osteoarthritis (KOA) rat model and its influence on proteins associated with the Wnt/β-catenin signaling pathway. Methods: A total of 32 specific-pathogen-free grade Sprague-Dawley rats were used. Eight rats were randomly selected as the control group (CG). The remaining 24 rats underwent intra-articular injections with 0.2 mL of 4% papain to prepare the KOA rat models. After the model was established, the 24 rats were randomly and equally assigned to 3 groups, including a model group (MG), a Tuina group (TG), and a positive medicine group (PMG), with 8 rats in each group. The Lequesne score was applied to evaluate the success of model development. After the model was successfully established, the CG did not receive any intervention, and the TG was treated with local, clockwise annular Rou-Kneading around the knee joint with the thumbs. The pressure in the longitudinal direction was 3 N, and the frequency was designed to be 120-140 times/min for 15 min, followed by flexing the joint 10 times. The PMG was intragastrically administered with celecoxib [24 mg/(kg·bw)] every day. These interventions were performed once a day, 6 d per week, for a total of 4 weeks. After treatment, the Lequesne score was applied again to assess the severity of the KOA in the rats; hematoxylin-eosin (HE) staining and a mixture of equal volumes of aqueous solutions of safranin O-fast green were used to stain and observe the cartilage morphology and structure; the modified Mankin score was applied to evaluate the pathology; enzyme-linked immunosorbent assay method was used to quantify the C-telopeptide fragments of type Ⅱ collagen (CTX-Ⅱ) and cartilage oligomeric matrix protein (COMP); Western blotting was then applied to quantify Wnt4, β-catenin, matrix metalloproteinase 13 (MMP-13), and bone morphogenetic protein 2 (BMP-2) protein expression; immunohistochemistry was conducted to determine the percentage of collagen type X (ColX)-positive cells. Results: The Lequesne score of the TG and PMG was both lower than that of the MG (P<0.01); the HE staining, safranin O-fast green stained morphology and structure, and modified Mankin scores of the TG and the PMG were also better than those in the MG (P<0.01). Compared with the CG, the amounts of CTX-Ⅱ and COMP in the serum were significantly increased (P<0.01); the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins in the cartilage tissue was significantly increased (P<0.01), and the percentage of ColX-positive chondrocytes was significantly increased (P<0.01) in the MG. In comparison with those in the MG, the amounts of CTX-Ⅱ and COMP were significantly decreased (P<0.01), the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins was significantly decreased (P<0.01), and the percentage of ColX-positive chondrocytes was significantly decreased (P<0.01) in the TG and PMG. Compared with the PMG, the contents of CTX-Ⅱ and COMP and the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins were decreased (P<0.05 or P<0.01); the percentage of ColX-positive chondrocytes was significantly decreased (P<0.01) in the TG. Conclusion: Tuina can relieve the degeneration of KOA, and the mechanism may be related to the down-regulation of the Wnt/β-catenin signaling pathway, the decrease in MMP-13 and BMP-2 protein expression, the reduction in chondrocyte extracellular matrix degradation, and slowing down the terminal cell differentiation.
5.Double-blind study of the efficacy and safety of desloratadine for treating allergic rhinitis
Yinan WANG ; Xianli YU ; Changyou JI ; Zhongzhan NI ;
Journal of Third Military Medical University 2003;0(18):-
Objective To evaluate the efficacy and safety of desloratadine for the treatment of allergic rhinitis. Methods A total of 50 cases of chronic or acute allergic rhinitis confirmed clinically were randomized into control and experimental groups for double blind study. Scoring of clinical symptoms, examinations of the nasal cavity, blood and urine routine examination, functions of liver and kidney and electrocardiogram (ECG) were conducted on day 14 before and after the experiment. The collected data were analyzed statistically. Results The clinical data of the two groups were comparable. The effective rate of desloratadine was significant in allergic rhinitis, being 95.45%. No remarkable adverse effect was noted in this experiment. Conclusion Desloratadine is more effective and safe than loratadine in the treatment of allergic rhinitis and it may be feasible for clinical application.
6.Prenatal diagnosis of mitochondrial disease: analysis of 28 pedigrees with mitochondrial DNA mutation
Yu LIU ; Ying ZHANG ; Xuefei ZHENG ; Hong PAN ; Yu QI ; Yinan MA
Chinese Journal of Perinatal Medicine 2017;20(9):679-683
Objective To perform a prenatal diagnosis for the second fetuses from 28 pedigrees with proband of mitochondrial disease due to mitochondrial DNA (mtDNA) mutation.Methods From April 2011 to November 2015,peripheral blood samples of 28 probands and their parents,urine samples of these probands and their mothers as well as amniotic fluid samples of the second fetuses from the 28 pedigrees were collected in Peking University First Hospital.DNA sequencing was used to identify mtDNA mutations.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to verify mutation sites,calculate mutation loads,and further confirm the diagnosis after birth.Microsatellite maker analysis was also performed on five short tandem repeats located in nuclear genes to exclude maternal contamination.Statistical analysis was carried out using independent t-test.Results In the 15 pedigrees carrying A3243G mutation,13 mothers and nine fetuses carried A3243G mutation.Neither the other two mothers nor their fetuses were positive for A3243G mutation.Among the 12 pedigrees with T8993G mutation,there were eight mothers carrying T8993G mutation and all of their fetuses carried the same mutation;and the other four mothers and their fetuses were negative for T8993G mutation.T10191C mutation was only found in one proband and the second fetus of that pedigree,but not in the mother.None of the fathers had mtDNA mutation.Results of PCR-RFLP were consistent with those of DNA sequencing.Short tandem repeat analysis demonstrated that amniocyte samples were from fetuses without maternal contamination.No mtDNA mutations were found in the six newborns who were negative for mtDNA mutations in prenatal diagnosis.The mean mutation load in urine samples of the six mothers without A3243G mutation in amniocytes was significantly lower than that of the nine mothers with A3243G mutation [(10.1 ±4.8) % vs (28.2 ± 15.1) %,t=2.290,P=0.043].Conclusions The lower the mtDNA mutation load in maternal urine samples,the less the possibility she bears a child with mtDNA mutation.However,prenatal diagnosis of mitochondrial disease is necessary.
7.Neuron-like differentiation of mesenchymal stem cells induced by quaternary chitosan thermosensitive hydrogel scaffolds combined with glial cell line-derived neurotrophic factor
Cheng HUANG ; Jiandong YANG ; Xinmin FENG ; Guangfeng LI ; Yinan LI ; Haixiang XIAO ; Yu SUN
Chinese Journal of Tissue Engineering Research 2013;(42):7420-7426
BACKGROUND:In recent years, chitosan-based thermosensitive hydrogel, as scaffold materials, have received more and more attentions in the field of tissue repair because of good biocompatibility, biodegradability and drug-sustained release.
OBJECTIVE:To explore the directed differentiation and growth of rat bone marrow mesenchymal stem cells on the quaternary chitosan thermosensitive hydrogel scaffold and to look for more ideal tissue engineering materials for the treatment of nervous system damage.
METHODS:The thermosensitive hygrogel scaffold was prepared using hydroxypropyltrimethyl ammonium chloride chitosan (HACC) andβ-glycerophosphate (β-GP). The spatial structure of scaffold was observed by scanning electronic microscope. Effect of leaching liquor from the HACC/β-GP scaffold on the viability of bone marrow mesenchymal stem cells was detected by (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The albumin from bovine serum was combined with the scaffold, and the slow-release effect of the scaffold was detected by ultraviolet absorption spectrometry. Bone marrow mesenchymal stem cells were incubated onto the compound scaffold at 3 passages. The adhesion, growth and differentiation of bone marrow mesenchymal stem cells on the compound scaffold were observed by the scanning electron microscope. Neuron-specific enolase was detected by immunofluorescence.
RESULTS AND CONCLUSION:The porosity and thermal sensitivity of HACC/β-GP scaffold and slow-release effect of glial cellline-derived neurotrophic factor were apparent. The results of MTT showed that the compound scaffold cannot take apparent negative effects to the proliferation of bone marrow mesenchymal stem cells. After inoculation, bone marrow mesenchymal stem cells permeated the porous structure of the scaffold and adhered to the scaffold. Under the role of glial cellline-derived neurotrophic factor, bone marrow mesenchymal stem cells showed neuron-like cellmorphology and cells co-cultured with the compound scaffold expressed the marker of neurons, neuron-specific enolase. Under the role of slow-release glial cellline-derived neurotrophic factor, bone marrow mesenchymal stem cells can grow wel in vitro and differentiate into neuron-like cells on the HACC/β-GP scaffold.
8.Effect of HbA1c meeting the standard or not on microalbuminuria,blood lipids and liver enzymes in patients with type 2 diabetes
Keying ZHANG ; Peng CAO ; Jian DU ; Yinan YU ; Yun LI ; Hongfei LUO
Journal of Chinese Physician 2011;13(2):167-169
Objective To investigate the effect of HbA1c meeting the standard or not on microalbuminuria,blood lipids and liver enzymes in patients with type 2 diabetes.Methods A retrospective analysis was performed on 457 subjects who had type 2 diabetes.They were divided into substandard group and standard group according to HbA1c result.The general information and relevant laboratory indicators of patients were.collected and compared between two groups.Results The microalbuminuria,serum triglyceride and liver enzymes (glutamyl transpeptidase,alkaline phosphatase,aspertate aminotransferase) were significantly different between two groups [ (189.8 ± 235.3) mg/dl vs (38.9 ± 85.5) mg/dl,(2.64 ± 2.99) mmol/L vs (2.02 ± 1.50)mmol/L,(41.7 ±52.9)U/L vs (29.7 ±24.9)U/L,(83.6 ±28.6) U/L vs (74.3 ±25.8)U/L,(26.7 ±19.1)U/L vs (22.0 ±10.5) U/L,P <0.05].HbA1c level was positively correlated with microalbuminuria,glutamyl transpeptidase and alkaline phosphatase (r =0.209,0.115,0.11,P <0.01).The microalbuminuria was an independent risk factor of affecting HbA1c to reach the standard (OR = 1.009,P <0.05).Conclusions HbA1c meeting the standard or not can influence many factors except blood glucose.
9.Expression of NF-κB p50 subunit in nodal peripheral T-cell lymphoma-uuspecified
Yinan WANG ; Hongmin LI ; Yu ZHAO ; Weidong LIU ; Shoudong MA ; Haishu YUE
Journal of Leukemia & Lymphoma 2009;18(3):149-151,154
Objective To study the expression of NF-κB p50 in nodal peripheral T-cell lymphomasunspecified (PTCL-U),and investigated the relationship between NF-κB and PTCL-U's complex biological behavior. Methods 51 patients with nodal PTCL-U were analysed by detecting the expression of NF-κB p50, p170 by immunohistochemistry and correlation between them and PTCL-U' s clinical feature, treatment effectiveness and prognosis were also studied. Results 11 patients(21.6 %, 11/51) and 31patients (60.8 %,31/51) were respectively positive for N F-κB p50 and p 170 expression. Expression of NF-κB were significantly correlated with p170 expression, poor performance status (PS>2) and non-complete remission in first line treatment(Spearman correlation= 0.459, 0.313, 0.284; P = 0.001, 0.025, 0.044). Overall survival rate of NFκB p50-positive PTCL-U was significantly lower than that of NF-κB p50-negative patients by Log-Rank test (P =0.0451). Multivariate analysis showed poor performance and higher Ki-67 were independent prognostic factor for PTCL-U, while NF-κB p50 was not. Conclusion The expression of NF-κB pS0 was correlated with muhidrug resistance and poor prognosis in nodal PTCL-U.
10.Prenatal diagnosis and genetic counseling of fragile X syndrome in four pedigrees by using high-resolution multiplex polymerase chain reaction
Hong PAN ; Songtao WANG ; Jie FU ; Xuefei ZHENG ; Pei PEI ; Yinan MA ; Yu QI
Chinese Journal of Perinatal Medicine 2017;20(3):172-176
Objectives To provide prenatal diagnosis and genetic counseling for four athigh-risk pregnant women with a suspected family or personal history of fragile X syndrome (FXS) by genetic screening of fragile X mental retardation (FMR1) gene.Methods This study was conducted on four pregnant women (No.l to 4) who received outpatient treatment in Peking University First Hospital from August 2014 to June 2016.Genomic DNA was extracted from peripheral blood samples of the pregnant women and six of their family members,four of which were suspected or confirmed FXS and the other two were FMR1 gene carriers.Amplide X kits were used to detect CGG repeat size in FMR1 gene.Two amniocytes and one chorionic villi samples were collected from three pregnant women to extract DNAs for FMR1 gene and karyotyping analyses.Results There were patients diagnosed with FXS in all the families by detecting CGG repeat numbers in FMR1 gene.The pregnant woman No.1 was a permutation carrier;No.2 carried normal FMR1 alleles while her brother had a mutation with over 20 CGG repeats in FMRI gene at chromosome X.No.3 and 4 were full mutation carriers with over 200 CGG repeats in FMR1 gene.After genetic counseling,No.3 decided to terminate the pregnancy due to abnormal fetal karyotype (47,XY,+21) and full mutation of FMR1 alleles.No.1 and 4 continued to pregnancy as their fetuses were normal in FMR1 alleles and karyotype.No.2 continued to pregnancy as her fetus was free of FXS risk.Conclusions Prenatal diagnosis and genetic counseling should be conducted on women at highrisk for FXS to avoid birth defects.People with a family history of FXS should be tested for FMR1 gene carrier status.