1.BML-111 attenuats acute lung injury induced by intestine ischemia-reperfusion via inhibiting p38 MAPK/NF-κB signaling pathway
Xue HAN ; Chuwen HU ; Hui LUO ; Weifeng YAO ; Shaoli ZHOU ; Quehua LUO ; Mian GE ; Ning SHEN
The Journal of Practical Medicine 2016;32(19):3139-3142
Objective This study aims to investigate the effect of Lipoxin A4 receptor on acute lung injury (ALI) induced by intestine ischemia-reperfusion (IIR). Methods Thirty-two 8-week old SD rats were randomly divided into four groups: sham, intestine ischemia-reperfusion (IIR), IIR + BML111 (BML-111), Boc-2 + IIR +BML111 (Boc-2). BML-111 (1 mg/kg) was given intraperitoneally at the onset of reperfusion in the BML-111 and the Boc-2 group. Boc-2 (50 μg/kg) was given intraperitoneally after anesthesia in the Boc-2 group. Rats were subjected to superior mesenteric artery occlusion consisting of 45-min ischemia and 6-h reperfusion, and the sham laparotomy was served as controls. The lung pathology was assayed by the H&E staining. Lung water content was detected using dry/wet ratio. Concentrations of TNF-α, IL-1β, and IL-6 in lung tissue were determined by ELISA. The protein expression of p38 MAPK and NF-κB of lung was assayed by western blot. Results IIR induced serious ALI, with poor lung pathology and increased lung water content, elevation of TNF-α, IL-1β, and IL-6 levels in lung, accompanied with activation of p38 MAPK/NF-κB pathway. However, BML-111 could inhibit the activation of p38 MAPK/NF-κB pathway, leading to the reductions of TNF-α, IL-1β, and IL-6 in lung and attenuation of IIR-induced ALI. Conclusion BML-111 treatment could attenuate inflammation in lung after IIR injury via inactivating the p38 MAPK/NF-κB signaling pathway.
2.Association between serum uric acid and different states of glucose metabolism and glomerular filtration rate.
Xiao-Ling CAI ; Xue-Yao HAN ; Li-Nong JI
Chinese Medical Journal 2010;123(21):3118-3122
BACKGROUNDRecently, it has been suggested that the serum uric acid (SUA) level decreased in diabetic patients. The aim of this study was to explore the association between SUA level and different state of glucose metabolism and glomerular filtration rate (GFR) reflected by the simplified Modification of Diet in Renal Disease (MDRD) equation and to test the hypothesis that high MDRD is one of the determinants of SUA level.
METHODSThis cross-sectional study included 2373 subjects in Beijing who underwent a 75 g oral glucose tolerance test (OGTT) for screening of diabetes. According to the states of glucose metabolism, they were divided into normal glucose tolerance, impaired glucose regulation and diabetes.
RESULTSMultiple stepwise linear regression analysis showed that adjusted by gender, SUA was positively correlated with body mass index (BMI), waist/hippo ratio, systolic blood pressure (SBP) and triglyceride, meanwhile negatively correlated with age, hemoglobin A1c, fasting insulin and MDRD. There was an increasing trend in SUA concentration and a decreasing trend in MDRD when the levels of fasting plasma glucose (FPG) increased from low to high up to the FPG level of 8.0 mmol/L; thereafter, the SUA concentration started to decrease with further increases in FPG levels, and the MDRD started to increase with further increases in FPG levels.
CONCLUSIONThis study confirmed the previous finding that SUA decreased in diabetes and provided the supporting evidence that the increased MDRD might contribute to the fall of SUA.
Adult ; Aged ; Blood Glucose ; metabolism ; Cross-Sectional Studies ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Linear Models ; Male ; Middle Aged ; Uric Acid ; blood
3.High-normal serum uric acid is associated with albuminuria and impaired glomerular filtration rate in Chinese type 2 diabetic patients.
Xiao-Ling CAI ; Xue-Yao HAN ; Li-Nong JI
Chinese Medical Journal 2011;124(22):3629-3634
BACKGROUNDRecently, some studies had shown that elevated serum uric acid (SUA) itself may increase the risk for development of renal disease in patients with diabetes. This study aimed to explore whether SUA was a predictor of microalbuminuria and impaired renal function in type 2 diabetes in Chinese patients.
METHODSThis cross-sectional study included 2108 type 2 diabetic patients. Kidney function was estimated using the simplified modification of diet in renal disease (MDRD) equation to obtain estimated glomerular filtration rate. The urine samples were obtained for measuring the albumin-to-creatinine ratio (ACR).
RESULTSAccording to the ACR level, these patients were divided into two groups, normal ACR (NA) and non-normal ACR (non-NA). Both SUA and creatinine were significantly higher in the non-NA group than those in the NA group ((318.89 ± 107.52) vs. (283.44 ± 88.64) µmol/L, and (95.08 ± 53.24) vs. (79.63 ± 18.20) µmol/L, respectively). Logistic regression analysis showed that diabetic duration, systolic blood pressure, creatinine and SUA were the independent predictors of albuminuria. Furthermore, to identify the factors associated with renal function, these patients were divided into two groups according to the MDRD level (MDRD < 90 or MDRD ≥ 90). Both SUA and creatinine were significantly higher in the lower MDRD group than those in the higher MDRD group ((301.90 ± 96.46) vs. (264.07 ± 84.74) µmol/L, and (89.10 ± 31.00) vs. (66.37 ± 11.15) µmol/L, respectively). Logistic regression analysis showed that only age and SUA were the independent predictors of MDRD.
CONCLUSIONHigh-normal SUA was associated with albuminuria and impaired glomerular filtration rate in Chinese type 2 diabetic patients.
Adult ; Aged ; Albuminuria ; blood ; physiopathology ; Diabetes Mellitus, Type 2 ; blood ; complications ; physiopathology ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Male ; Middle Aged ; Uric Acid ; blood
4.Meta-analysis of the association of Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma gene with type 2 diabetes in Chinese Han population.
Wu-Lan GUO ; Yong TANG ; Xue-Yao HAN ; Li-Nong JI
Acta Academiae Medicinae Sinicae 2011;33(6):593-599
OBJECTIVETo evaluate the association of Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma (PPARgamma) gene with type 2 diabetes (T2DM) in Chinese Han population.
METHODSThe present investigation was carried out using the keywords "PPARgamma", "pparg", "Pro12Ala", "type 2 diabetes", and "Chinese. The odds ratios (OR) for Ala12 used as the metric of choice were calculated in the dominant and additive model separately. The Meta-analysis was conducted by software STATA 11.0.
RESULTS(1) We identified 22 studies, of which 17 studies involving 3927 type 2 diabetes cases and 3364 controls fell into the inclusion criteria. The analysis indicated no significant inter-study heterogeneity and publication bias. (2) The frequencies of the minor allele Ala12 in type 2 diabetes and control groups were 4.8% and 4.6% respectively. (3) The combined overall OR of dominant and additive model calculated by fix-effects meta-analysis for type 2 diabetes and the Pro12Ala polymorphism, were 0.95 (95% CI: 0.80, 1.12) and 0.93 (95% CI: 0.79, 1.09) respectively.
CONCLUSIONIn this meta-analysis, the Pro12Ala gene variant (rs1801282) is not found to be associated with the susceptibility for type 2 diabetes in Chinese Han population.
Asian Continental Ancestry Group ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; PPAR gamma ; genetics ; Polymorphism, Genetic
5.Analysis of genetic variation diversity of porcine circovirus-2 virus genome isolated from Shanxi area
Xin WU ; Fan MENG ; Jingming YAO ; Zhenhua FAN ; Juanping WANG ; Yichao HAN ; Ruijuan MI ; Yipeng XUE ; Yue ZHAO ; Wenjun LIU
Chinese Journal of Veterinary Science 2017;37(8):1442-1450
In order to study genetic variation diversity of porcine circovirus type 2 (PCV2) strains in Shanxi,the genomic sequences of nine PCV2 strains including SXQX,SXCZ,SXTY2,SXJC,SXJX,SXLL,SXPY,SXPG and SXXY recently isolated from some areas of Shanxi from 2013 to 2016,was cloned,sequenced and received by GenBank.The amplified PCV2 genomic sequences,ORF2 sequences and Cap protein amino acid of these nine strains were analysed and compared with those of published 28 PCV2 strains by DNAStar,drawing phylogenetic tree.The results showed that the genomic sequences of SXJX,SXJC and SXXY PCV2 strains were 1 768 bp,and the others were 1 767 bp,which accounted for 33% and 67%,respectively.The homologies of nucleotide sequences of the nine strains were 94.7%-99.8%,the homologies of nucleotide sequences of the nine strains with the 28 isolates from different regions of the world PCV strain were 93.9%-99.9%,and the homologies of nucleotide sequences of the nine strains with the domestic vaccine strains were 95.1%-99.8%.The phylogenetic analysed that SXJX,SXJC and SXXY belonged to genotype PCV-2D,SXLL,SXPY and SXCZ belonged to genotype PCV-1C,and SXTY14,SXPG and SXQX belonged to genotype PCV-1A/1B.Thus it proved that the epidemic strain of PCV2 was mainly PCV-2b in Shanxi.The homologies of ORF2 nucleotide sequences and Cap amino acid of the nine strains were 90.0%-100.0% and 87.1 %-100.0% respectively,the homologies of ORF2 nucleotide sequences and Cap amino acid of the nine strains with the 28 isolates from different regions of the world PCV strain were 87.6%-100.0% and 84.1%-100.0% respectively,and the homologies of ORF2 nucleotide sequences and Cap amino acid of the nine strains with the domestic vaccine strains were 91.0%-100.0% and 89.3%-100.0% respectively.The Cap amino acids of SXQX,SXJX,SXTY14,SXPG,SXJC and SXXY PCV2 were 233,ORF2 of SXQX,SXTY14 and SXPG located at 1 033-1 734 bp,ORF2 of SXXY,SXJX and SXJC located at 1 033-1 734 bp,and the Cap amino acids of SXCZ,SXLL and SXPY PCV2 were 234,ORF2 of them located at 1 030-1 734 bp,in addition,the positions of 1 030-1 734 bp were more three bases TCA than other ORF2 genome sequence of 1 767 bp,resulting in increasing a K (Lys) of amino acid sequencein at the 234 position.Also Cap protein of 9 PCV2 strains showed more amino acid variation in addition to the only high-ly conserved glycosylation sites (NYS) (pp.143-145 amino acid).It provided theoretical basis for the PCV2 immune prevention of research in Shanxi,and the data of basic theory of molecular pathogenesis of PCV2.
6.Efficient and rapid liquid reduction animal model.
Bing HAN ; Shu-ming KOU ; Biao CHEN ; Yao-zong PENG ; Yue WANG ; Yu-long HAN ; Xiao-li YE ; Xue-gang LI
China Journal of Chinese Materia Medica 2015;40(22):4446-4451
To investigate the practicability of establishing zebrafish lipid-lowering drug screening model and the effect of berberine (BBR) on hyperlipidemic zebrafish. Three-month-old zebrafishes were fed with 4% cholesterol for 0, 2, 4, 8, 14, 20, 25, 30 days, and the level of total cholesterol in serum was measured. Zebrafish were randomly divided into four groups: the control group, the high cholesterol diet group, the 0.01% simvastatin-treated group, the 0.1% berberine-treated group and the 0.2% berberine-treated group. The levels of total cholesterol (TC), triglyceride (TC), low density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) in serum were measured; the expression of hepatic HMGCR, LDLR and CYP7A1a mRNA expressions were detected by real time PCR. Oil red O staining was performed to observe the changes in fat content in the liver. According to the result, the level of serum TC in the 4% cholesterol diet group significantly was higher than that of the normal control group in a time-dependent manner and reached a stable level at the 20th day. The BBR group showed significant decreases in the levels of TC, TG and LDL-c, HMGCR mRNA expression and fat content and increases in LDLR and CYP7A1a mRNA. The hyperlipidemia zebrafish model was successfully established by feeding with 4% cholesterol for 20 days. The findings lay a foundation for further screenings on lipid-lowering drugs.
Animals
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Berberine
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administration & dosage
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Cholesterol
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metabolism
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Disease Models, Animal
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Drugs, Chinese Herbal
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administration & dosage
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Female
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Humans
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Hyperlipidemias
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drug therapy
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metabolism
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Hypolipidemic Agents
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administration & dosage
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Liver
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drug effects
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metabolism
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Male
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Triglycerides
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metabolism
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Zebrafish
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metabolism
7.Application of immune function test to evaluate effect of cytokine-induced autologous killer cell infusion for elderly patients with hematological malignancies.
Li-Li CAI ; Bo YANG ; Xue-Chun LU ; Hong-Li ZHU ; Wei-Dong HAN ; Yao WANG ; Yang LIU ; Han-Ren DAI ; Shan-Qian YAO
Journal of Experimental Hematology 2010;18(5):1250-1255
The aim of study was to explore the efficacy of cytokine induced autologous killer (CIK) cell infusion as an immune therapy for elderly patients with hematological malignancies. Peripheral blood mononuclear cells (PBMNC) were isolated from 20 elderly patients with hematological malignancies, and then augmented by priming with human recombinant interferon gamma (rhIFN-γ) followed by human recombinant interleukin 2 (rhIL-2) and monoclonal antibody (mAb) against CD3. The obtained autologous CIK cells [(2-3)×10(9)] were infused back to individual patients, then followed by subcutaneous injection of IL-2 at single daily dose of 1×10(6) U for 10 consecutive days. The regimen was repeated every 4 weeks and total 136 cycles of CIK cells transfusion were completed. The changes in cellular immune function, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life (QOL) and survival were assessed. The results indicated that 14 patients received 8 cycles of CIK cells infusion, and 4 cycles were completed in 6 patients. No adverse reaction was observed in all patients. The percentages of CD3+, CD3+CD8+ and CD3+CD56+ cells increased significantly (p<0.05), and serum levels of β2-microglobulin and LDH markedly decreased (p<0.05) after autologous CIK cells transfusion. The tumor-related symptoms were relieved, QOL obviously improved (p<0.01) in all patients. Complete remission was seen in 11 patients, and partial remission was observed in 7 patients. It is concluded that the autologous CIK cell infusion can improve immunity in elderly patients of hematological malignancies and displays its effectiveness and safety for elderly patients.
Aged
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Aged, 80 and over
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Carcinoma, Hepatocellular
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immunology
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therapy
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Cytokine-Induced Killer Cells
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Female
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Hematologic Neoplasms
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immunology
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therapy
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Humans
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Immunotherapy, Adoptive
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methods
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Killer Cells, Natural
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immunology
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Male
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Middle Aged
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Treatment Outcome
8.Clinical study of autologous cytokine induced killer cells combined with IL-2 for therapy of elderly patients with B-cell malignant lymphoma.
Bo YANG ; Xue-Chun LU ; Hong-Li ZHU ; Wei-Dong HAN ; Yao WANG ; Hui FAN ; Su-Xia LI ; Yang LIU ; Han-Ren DAI ; Shan-Qian YAO
Journal of Experimental Hematology 2010;18(5):1244-1249
Objective of this study was to evaluate the effectiveness and safety of autologous cytokine induced killer (CIK) cells combined with IL-2 in treatment of elderly patients with B-cell malignant lymphoma. Peripheral blood mononuclear cells (PBMNC) were isolated from 9 elderly patients with B-cell malignant lymphoma, and then induced into CIK cells by IFN-γ, IL-2 and monoclonal antibody (mAb) against CD3. The autologous CIK cells [(2-3)×10(9)] thus obtained were infused back to individual patients, then followed by subcutaneous injection of IL-2 at single daily dose of 1×10(4) U/day for 10 consecutive days. The regimen was repeated every 4 weeks and total 64 cycles of CIK cell transfusion were completed. The changes in cellular immune function, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life and survival time were assessed. 7 patients received 8 cycles of CIK cell infusion, and 4 cycles were completed in 2 patients. The results showed that no adverse reaction was observed in all above mentioned patients. The percentages of CD3+, CD3+CD8+ and CD3+CD56+ increased significantly (p<0.05), and serum levels of β2-microglobulin and LDH were markedly decreased (p<0.05) after autologous CIK cell transfusion. The lymphoma symptoms were relieved with quality of life obviously elevated (p<0.01) in all patients. Complete remission was seen in 8 patients. Though one patient received 8 cycles of CIK cell transfusion therapy and achieved transient very good partial remission, but he died of acute large-area myocardial infarction and persistent progression of lymphoma. In conclusion, regimen of autologous CIK cells combined with IL-2 is safe and effective for the therapy of elderly patients with B-cell malignant lymphoma.
Aged
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Aged, 80 and over
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Cytokine-Induced Killer Cells
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immunology
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Female
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Humans
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Immunotherapy, Adoptive
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Interleukin-2
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therapeutic use
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Killer Cells, Natural
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immunology
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Lymphoma, B-Cell
;
therapy
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Male
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Middle Aged
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Treatment Outcome
9.Clinical study of autologous cytokine induced killer cell infusion treating for elderly patients with myelodysplastic syndrome.
Yang LIU ; Er-Ning BAO ; Bo YANG ; Xue-Chun LU ; Hong-Li ZHU ; Wei-Dong HAN ; Yao WANG ; Han-Ren DAI ; Shan-Qian YAO
Journal of Experimental Hematology 2011;19(3):787-792
Objective of this study was to evaluate the effectiveness and safety of autologous cytokine induced killer (CIK) cells combined with IL-2 in treatment of elderly patients with myelodysplastic syndromes (MDS). Peripheral blood mononuclear cells were isolated from 6 elderly MDS patients and were stimulated by cytokines in vitro to form CIK cells. The autologous CIK cells were then infused back into the corresponding patients. The regimen was repeated every 4 weeks. Effector cell proportion changes, adverse effects, effects on inflammation, hemoglobin level and blood transfusion were assessed after treatment. The results showed that after autologous CIK cell infusion, the percentages of CD3(+), CD3(+)CD8(+) and CD3(+)CD56(+) increased significantly (p < 0.05). No severe adverse effects were observed in all patients. It also significantly reduced inflammation frequency and shortened high fever duration. During stable stage of disease, the CIK cell infusion could reduce the red blood cell infusion amount and stabilize hemoglobin level. However, the natural course of transformation from myelodysplastic syndromes to high-risk subtypes could not be changed by CIK cell treatment. It is concluded that the autologous CIK cell infusion is a safe and effective therapy for geriatric myelodysplastic syndrome.
Aged
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Aged, 80 and over
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Cytokine-Induced Killer Cells
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Humans
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Immunotherapy, Adoptive
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Lymphocyte Transfusion
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Male
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Myelodysplastic Syndromes
;
therapy
10.The mutations of the D-loop hypervariable region II and hypervariable region III of mitochondrial DNA in oral squamous cell carcinoma.
Yao-zhong WANG ; Mu-yun JIA ; Rong-tao YUAN ; Guo-dong HAN ; Ling-xue BU
West China Journal of Stomatology 2010;28(3):254-260
OBJECTIVETo investigate the frequency of mitochondrial DNA (mtDNA) D-loop hypervariable region II (HVR II) and hypervariable region III (HVR III) mutations in oral squamous cell carcinoma (OSCC) and their correlation to provide the new targets for the prevention and treatment of OSCC.
METHODSThe D-loop HVR II and HVR III regions of mtDNA in seven cases with OSCC tissues, matched with paracancerous tissues and normal mucosa tissues from the same case, were amplified by polymerase chain raction (PCR), then were detected by direct sequencing to find the mutantsites after the comparison of all sequencing results with the mtDNA Cambridge sequence in the GenBank database.
RESULTS82 (56 species) nucleotide changes, with 51(26 species) nucleotide polymorphism, were found after the comparison of all sequencing results with the mtDNA Cambridge sequence in the GenBank database. 31(30 species) mutations, with 21 located within the HVR II and HVR III regions, were found in 3 tumor tissue samples, their paracancerous and normal mucosa tissue were found more polymorphic changes but no mutation. The mtDNA D-loop HVR II and HVR III regions mutation rate was 42.9% (3/7) in OSCC.
CONCLUSIONThe mtDNA D-loop HVR II and HVR III regions were highly polymorphic and mutable regions in OSCC. It suggested that the D-loop HVR II and HVR III regions of mtDNA might play a significant role in the tumorigenesis of OSCC. It may become new targets for the gene therapy of OSCC by regulating the above indexes.
Carcinoma, Squamous Cell ; DNA, Mitochondrial ; Female ; Humans ; Mouth Neoplasms ; Mutation ; Polymorphism, Genetic