Yue H.,The First Peoples Hospital Of Jining |
Han W.,The First Peoples Hospital Of Jining |
Sheng L.,The First Peoples Hospital Of Jining
International Journal of Clinical and Experimental Medicine | Year: 2017
Objective: The progressive neurodegenerative process in Alzheimer’s disease (AD) is accompanied by chronic inflammation, including activation of microglia and astrocytes that express pro-inflammatory cytokines. Up to now, numerous studies of genetic epidemiology have assessed the association of pro-inflammation cytokines gene polymorphisms and risk of AD in different populations, but conflicting results were obtained due to the heterogeneity of the genetic background among populations. Methods: Here, we recruited 248 AD patients, and 226 matched healthy controls from Shandong Province to evaluate the influence of IL-6 rs1800795, IL-12 rs3212227 and TNF-α rs1800629 polymorphism patients with AD. Single nucleotide polymorphism locus was genotyped using PCR-RFLP. Results: The genotypic and allelic frequency of TNF-α, IL-6 did not show significant difference between AD and normal controls. However, the frequency of wild (AA) and homozygous mutant (CC) genotype IL-12 rs3212227 genotypes in cases and controls was found more in controls (43% and 5.7% respectively), but that of the heterozygous genotype was higher (60.15%) in cases with AD patients. Conclusion: Though no any relationship between IL-6, and TNF-α genotypes or alleles and AD susceptibility was revealed, we first identified IL-12 rs3212227 AC genotype confer genetically susceptibility to AD in Chinese population. © 2017, E-Century Publishing Corporation. All rights reserved.
Zhou S.,The First Peoples Hospital of Jining |
Jiao F.,The First Peoples Hospital of Xianyang City |
Li X.,The First Peoples Hospital of Jining |
Lv L.,The First Peoples Hospital of Jining |
Yang X.,The First Peoples Hospital of Jining
International Journal of Clinical and Experimental Pathology | Year: 2017
The aim of this study was to determine serum levels of soluble IL-7R (sIL-7R) in systemic lupus erythematosus (SLE) patients with lupus nephritis and its correlation with disease activity. For this cross-sectional study, 66 patients (20 males and 46 females) with lupus nephritis and 56 age-matched healthy controls (18 males and 38 females) were recruited. Serum sIL-7R levels (ng/mL) were determined by a sandwich ELISA kit. Disease activity was measured by SLE disease activity index (SLEDAI) score, 24 h proteinuria, serum creatinine levels, glomerular filtration rate (GFR), and levels of complement C3 (C3), C4, and C1q. We found that serum sIL-7R level was 67.7% significantly higher in patients with lupus nephritis (1693.6 ± 812.4 vs. 2785.5 ± 1173.5 ng/mL, P < 0.0005). Patients with active nephritis (n=32) had significantly higher serum sIL-7R than those in disease remission (n=34) (3255.4 ± 1583.5 vs. 2186.5 ± 1062.8 ng/mL, P=0.002). Serum sIL-7R levels correlated significantly with disease activity markers with |r| ranging from 0.330 to 0.445 (all P < 0.05). Higher serum sIL-7R levels were associated with lower C3, C4, C1q, and GFR and with higher 24 h proteinuria, serum creatinine levels, and SLEDAI scores. In conclusion, our results indicate that sIL-7R could be a valuable marker of disease activity in lupus nephritis.
Tian F.,The First Peoples Hospital of Jining |
Wei H.,The First Peoples Hospital of Jining |
Jia T.,Health Board of Jinan
Biomedical Chromatography | Year: 2014
Existing methods to determine oxyresveratrol, a trans-polyphenolic stilbene, lack selectivity, require large plasma sample volumes or have time-consuming sample preparation and chromatographic isolation. Here an improved highly sensitive liquid chromatography-tandem mass spectrometry method was developed to determine low oxyresveratrol concentrations in rat plasma. The plasma samples were prepared by liquid-liquid extraction with acetoacetate. The analytes were separated on Venusil hydrophilic interaction chromatography (HILIC) column (2.1×50 mm, 5.0 μm) guarded by a HILIC column (4×3.0 mm, 5.0 μm). The mobile phase consisted of acetonitrile-water (containing 1 mmol/L ammonium formate) at gradient elution mode with a flow rate of 0.3 mL/min. Resveratrol was used as the internal standard. An electrospray ionization source was applied and operated in the negative multiple reaction monitoring (MRM) mode. Oxyresveratrol and resveratrol were detected on MRM by the transitions from the precursor to the product ion (m/z 243.1→175.1 and 227.1→143.0). The total running time was 5 min and the retention times of oxyresveratrol and resveratrol were 1.97 and 1.82 min. Chromatograms showed no endogenous interfering peaks with blank samples. The linear calibration curve was obtained over the concentration range of 1-500 ng/mL. The injection volume was 10 μL and the limit of quantification was 1 ng/mL. The extraction recovery varied from 78.2 to 84.3% for low, medium and high quality control samples. At the same time, the intra- and inter-day relative standard deviations were <6.78 and <10.02%, respectively, while the corresponding intra- and inter-day accuracy relative error values fell in the range of 3.75-6.67%. The HPLC-MS/MS method was successfully applied to a pharmacokinetics study, in which the experimental rats received a single dose of oxyresveratrol (10 mg/kg, intragastric administration). The pharmacokinetic results are presented. © 2013 John Wiley & Sons, Ltd.
Lu J.,The First Peoples Hospital Of Jining |
Sun P.,The Affiliated Hospital of Jining Medical College |
Sun B.,The Second Peoples Hospital Of Jining |
Wang C.,The First Peoples Hospital Of Jining
Medical Science Monitor | Year: 2015
Background: The present study aimed to compare the expression of liver kinase B1 (LKB1) in prostate cancer (PCa) tissues and the paired adjacent tissues, then to evaluate the statistical relationship between LKB1 expression and prognosis of PCa patients. Material/Methods: The relative expression of LKB1 at mRNA level was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of LKB1 at protein level was measured by immunohistochemistry (IHC) method. The relationship between LKB1 expression and clinicopathologic characteristics was estimated by chi-square test. Kaplan-Meier method was used to analyze the overall survival of PCa patients with different LKB1 expression. Cox regression analysis was performed to estimate the significance of LKB1 expression and clinicopathologic characteristics in the prognosis of PCa patients. Results: The relative expression of LKB1 at mRNA level was significantly lower in PCa tissues than in the normal tissues (P<0.001). The LKB1 expression was proved to be affected by clinical stage (P=0.019) and PSA concentration (P=0.031) of PCa patients. Moreover, patients with negative LKB1 expression had shorter survival than those with positive expression. Cox regression analysis confirmed that LKB1 could be regarded as a prognostic biomarker for PCa patients (P=0.001, HR=3.981, 95% CI=1.698–9.336). Conclusions: The expression of LKB1 was lower in PCa tissues and might be a predictor for the prognosis of PCa patients. © Med Sci Monit, 2015.
Tian D.-H.,The First Peoples Hospital of Jining
International Eye Science | Year: 2014
AIM: To study the correlation between and the peripapillary retinal nerve fiber layer (RNFL) thickness, structure changes in non-proliferative diabetic retinopathy (NPDR) and the the changes of visual function METHODS: Eighty cases (80 eyes) of patients with NPDR who were in our hospital from January 2011 to December 2013 as group NPDR, 60 cases of patients (60 eyes) without retinopathy who were in the hospital were selected as non-diabetic retinopathy group (NRD) group, meanwhile, 50 healthy people who had health examination in our hospital as control group. The RNFL thickness and visual electrophysiological testing were performed on the study objects in the three groups, and the results were compared among groups. RESULTS: Group NPDR's above, below, nasal, temporal and average RNFL thickness were 91.52±18.52, 88.63±21.65, 63.62±11.72, 60.42±9.13, 69.36±12.52μm, those of group NPDR were 111.32±21.90, 113.57±22.67, 74.31±11.74, 67.64±12.34, and 97.31±11.43μm, those of group control were 121.65±21.42, 129.32±23.31, 82.42±9.28, 80.32±8.51, 102.54±21.82μm. To compare of average thickness of RNFL of three groups, groups NPDR and NPD were thinner than that of control group; To compare each quadrant phase, above, below, nasal, the RNFL thickness among three groups had statistical significance (P<0.05), while nasal sides had no obviously changes (P>0.05); At the same time, 60'P100 latency (MS), 60'P100 amplitude (V), 15'P100 latency (MS) and 15'P100 amplitude (V) of three groups had statistical significance (P<0.05). CONCLUSION: The changes of RNFL thickness have occurred in the early time of NPDR, and mainly the above, below and temporal, and it has a significant relevance with the changes of visual function. Copyright 2014 by the IJO Press.
Zhang X.,The First Peoples Hospital of Jining |
Zhang L.,The First Peoples Hospital of Jining
Chinese Journal of Rehabilitation Medicine | Year: 2014
Method: A focal cerebral ischemia model of rat was established by embolizing left middle cerebral artery with autologous blood clots. Ninety healthy Sprague-Dawley rats were randomly divided into 3 groups: sham group, CIMT group,and focal cerebral ischemia (MCAO) group, 30 in each group. The CIMT group rats were forced to use their impaired limbs by placing their nonimpaired fore-limbs in casts at the 7th day after MCAO. The behavior scores were evaluated. Expressions of GAP-43, SYPmRNA and protein were detected by means of in situ hybridization histochemistry technique and immunohistochemistry.Objective: To investigate the effects of constraint-induced movement therapy (CIMT) on the expressions of growth-associated protein 43 (GAP-43) and synaptophysin (SYP) after focal cerebral ischemia in rats.Result: Compared with MCAO group, the scores of neurological deficit were significantly lower,and the expressions of GAP-43, SYPmRNA and protein were obviously higher in CIMT group.Conclusion: CIMT could improve neurological function of rats after cerebral ischemia. The possible mechanism was closely related to up-regulation of expressions of GAP-43 and SYP, thus to improve neural plasticity.
PubMed | The First Peoples Hospital of Jining and Jining Medical University
Type: Journal Article | Journal: Fundamental & clinical pharmacology | Year: 2016
Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and still remains therapeutically a challenge. A strategy to target NSCLC is to identify agents that are effective against NSCLC cells while sparing normal cells. We show that tigecycline, an FDA-approved antibiotic drug, preferentially targets NSCLC cells. Tigecycline is effective in inhibiting proliferation and inducing apoptosis of multiple cell lines derived from two common NSCLC subtypes: adenocarcinoma and squamous cell carcinoma. Tigecycline also dose-dependently inhibits colony formation of NSCLC subpopulation of cells with highly proliferative and invasive properties. Compared to NSCLC cells, tigecycline affects proliferation and survival of normal fibroblast cells significantly to a less extent. More importantly, tigecycline significantly inhibits NSCLC tumor growth through decreasing proliferation and increasing apoptosis of tumor cells in vivo. Tigecycline significantly inhibits mitochondrial respiration, mitochondrial membrane potential, and ATP levels and increases reactive oxygen species (ROS), suggesting that tigecycline impairs mitochondrial functions. Our study suggests that tigecycline may be a useful therapeutic agent, and inhibiting mitochondrial functions may represent a new targeted therapy for NSCLC.
PubMed | P.A. College and The First Peoples Hospital of Jining
Type: Journal Article | Journal: Molecular medicine reports | Year: 2016
The present study aimed to investigate the role of the soluble programmed death1 (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) during the progression of rheumatoid arthritis (RA). From October 2012 to May 2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry. Expression of sPD1 in Treg was detected by western blot analysis. Immunosuppressive activity of CD4+CD25 Treg was measured via thiazolyl blue in an MTT assay. ELISA was used to detect interleukin10 (IL10), transforming growth factor beta (TGF-), interleukin-4 (IL-4), interferon (IFN-) and nuclear factor of activated T cells (NFAT). It was observed that in peripheral blood, CD4+CD25-FOXP3+/CD4+ levels were reduced in the RA group (P<0.001), and sPD1 levels were markedly higher (P<0.001), compared with the HC group. Additionally, it was observed that relative sPD1 protein expression in the small interfering RNA (siRNA)-sPD-1 treated group was reduced compared with the untreated and scrambled siRNA groups (all P<0.0001). The mean fluorescence intensity of CTLA-4 and Foxp3 decreased markedly upon transfection with siRNA-sPD-1 (P<0.001). Compared with the normal CD4+CD25 T group, optical density (OD)540 values, IFN-/IL-4 concentration ratio and NFAT activity in siRNA untreated and scramble groups reduced significantly (all P<0.001). OD540 value, IFN-/IL-4 concentration ratio and NFAT activity in the siRNAsPD1 group were significantly upregulated (all P<0.001). Therefore, sPD-1 may suppress the level of CD4+CD25 Tregs in the peripheral blood of RA patients, and may be involved in a variety of immune processes mediated by CD4+CD25 Tregs.
PubMed | P.A. College and The First Peoples Hospital of Jining
Type: Journal Article | Journal: Oncology letters | Year: 2017
The present study aimed to identify polypeptides that specifically bond to breast cancer stem cells from a phage display random 12 peptide library, in addition to the affinity and specificity of polypeptides. A phage display random 12 peptide library was screened using breast cancer stem cells as targets isolated from the MDA-MB-231 cell line using the serum-free culture technique with hs578bst and MDA-MB-231 cells as subtract-screening cells. Positive and specific binding clones were amplified and sent for sequencing. The affinity and specificity of the positive clones were subsequently identified by ELISA and 3,3-diaminobenzidine staining. The results demonstrated that phages were gathered ~500 times following three rounds of biopanning. ELISA identified that the affinity to breast cancer stem cells of the no. 6 phage was 6.14 times higher than that in the control group. In addition, immunohistochemistry observed that the no. 6 phage exhibited high-specificity bonding to breast cancer stem cells, and the peptide sequence of the positive phage was GYSASRSTIPGK following DNA sequencing and translation. Thus, the present study isolated a specific peptide that bonds to breast cancer stem cells from a phage display random peptide library, which may facilitate further studies regarding the stem cell-targeted therapy of breast cancer.
PubMed | The First Peoples Hospital of Jining and Shandong University
Type: | Journal: Computer methods and programs in biomedicine | Year: 2016
Antibacterial peptides (ABPs) are essential components of host defense against microbial infections present in all domains of life. The AMPs incorporating unnatural amino acids (uABPs) exhibit several advantages over naturally occurring AMPs based on factors such as bioavailability, metabolic stability and overall toxicity.Computer-aided modeling and in vitro susceptibility test were combined to rationally design short uABPs with potent antimicrobial activity. In the procedure, peptide characterization and machine learning modeling were used to develop statistical regression predictors, which were then employed to guide the molecular design and structural optimization of uABPs, to which a number of commercially available unnatural amino acids were introduced.An improved uABP population was obtained, from which several promising candidates were successfully prepared and their antibacterial potencies against three bacterial strains Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli were measured using broth microdilution assay. Consequently, four uABPs with hybrid structure property were determined to have high potency against the tested strains with minimum inhibitory concentration (MIC) of <50g/ml.Molecular dynamics (MD) simulations revealed that the designed uABPs are amphipathic helix in solution but they would largely unfold when spontaneously embedding into an artificial lipid bilayer that mimics microbial membrane.