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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.

Lu J.,The First Peoples Hospital of Jining | Zhong F.,Shandong Academy of Sciences | Sun B.,The Second Peoples Hospital of Jining | Wang C.,The First Peoples Hospital of Jining
International Journal of Clinical and Experimental Pathology | Year: 2016

Background: The heparan sulfate 6-O-endosulfatase 2 (SULF2) promotes growth and metastasis of solid tumors and is linked with the prognosis of various tumors. In the present study, we aimed to detect the expression of SULFs and estimate its prognostic relevance in prostate cancer (PCa) patients. Methods: The relative expression of SULF2 in 128 PCa tissues and 53 healthy tissues at mRNA and protein level were evaluated by qRT-PCR and western blot, respectively. The association between SULF2 expression and clinical factors as well as overall survival was severally assessed using chi-square test and Kaplan-Meier analysis. Meanwhile, cox regression analysis was applied to evaluate the independent prognostic significance of SULF2. Results: The relative expression levels of SULF2 was significantly higher in tumor tissues compared with healthy tissues both at mRNA and protein level (P<0.05). And the high expression of SULF2 was correlated with PSA, metastasis, and tumor stage. Kaplan-Meier analysis indicated that patients with high SULF2 expression had a poor overall survival than those with low expression (log rank test, P=0.000). Moreover, multivariate analysis showed that increased expression of SULF2 was an independent predictor of the prognosis of PCa. Conclusion: Our data indicated that SULF2 was up-regulated and might be a novel prognostic indicator in PCa.

Dong P.,Shandong University | Zhao J.,The Peoples Hospital of Chiping | Zhang Y.,The First Peoples Hospital of Jining | Dong J.,Shandong University | And 6 more authors.
Neuroscience | Year: 2014

Aging is associated with exacerbated brain injury after ischemic stroke. Herein, we explored the possible mechanisms underlying the age-associated exacerbated brain injury after ischemic stroke and determined whether therapeutic intervention with anesthetic post-conditioning would provide neuroprotection in aged rats. Male Fisher 344 rats (young, 4. months; aged, 24. months) underwent 2. h of middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion, with or without sevoflurane post-conditioning for 15. min immediately at the onset of reperfusion. Compared with young rats, aged rats showed larger infarct size, worse neurological scores and more TUNEL-positive cells in the penumbral cerebral cortex at 24. h after MCAO. However, edema formation and motor coordination were similar in both groups. Sevoflurane reduced the infarct size, edema formation, and TUNEL-positive cells, and improved the neurological outcome in young rats but not in aged rats. Molecular studies revealed that basal expression of the anti-apoptotic molecule B-cell lymphoma-2 (Bcl-2) in the brain was lower in aged rats compared with young rats before MCAO, while basal expression of the pro-apoptotic molecule Bcl-2-associated X protein (Bax) showed similar levels in both groups. MCAO reduced Bcl-2 expression and increased Bax expression in both groups; however, Bax increase was more pronounced in aged rats. In young rats, sevoflurane reversed the above MCAO-induced changes. In contrast, sevoflurane failed to enhance Bcl-2 expression but decreased Bax expression in aged rats. These findings suggest that aging-associated reduction in basal Bcl-2 expression in the brain contributes to increased neuronal injury by enhancing cell apoptosis after ischemic stroke. Sevoflurane post-conditioning failed to provide neuroprotection in aged rats, probably due to its inability to increase Bcl-2 levels and prevent apoptosis in the brain. © 2014 IBRO.

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.

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