Thrombopoietin (TPO) is a major cytokine for megakaryocytopoiesis and thrombopoiesis, and also plays an important role in the regulation of early hematopoiesis. TPO activates a number of signal pathways to exert its biological function by binding to its receptor (c-mpl). Once these signal pathways (including Jak/STAT, PI3K/Akt, Ras/MAPK) are activated, the expression of the downstream signal molecules can be changed, which then induces biological effects. Recent researches have suggested the novel functions of TPO in many systems. The receptor of TPO (c-mpl) has been shown not only present in hematological cells, but also in many other cells and organs, such as neurons, heart muscle cells, vessel endothelial cells and so on. TPO exerts a protective effect on these cells through the interaction with c-mpl. This review discusses the molecular mechanism of TPO signal and the effect of TPO on multi-nonhematopoietic cells.
Animals ; Humans ; Myocytes, Cardiac ; Neurons ; Signal Transduction ; genetics ; Thrombopoietin ; genetics ; metabolism

Objective To compare the clinical outcomes between conventional percutaneous vertebroplasty (PVP) and targeted PVP in the treatment of osteoporotic vertebral compression fractures (OVCFs).Methods A retrospective cohort study was designed to review 215 cases of single level OVCFs hospitalized between January 2014 and December 2015.According to the procedure techniques,the patients were assigned to targeted PVP group (89 cases) and conventional PVP group (126 cases) which was further divided into sufficient filled subgroup (110 cases) and insufficient filled subgroup (16 cases) on basis of cement distribution.Key techniques of targeted PVP included accurate needle insertion to fractured area and cement injection using a push rob with a side opening.Operating time,cement injection volume,rate and types of cement leakage,cement distribution in the fractured area and visual analogue score (VAS) of back pain were compared between the two groups.Results Operating time in targeted PVP group was longer than that in conventional PVP group (P ＜ 0.05).There were no significant differences in cement injection volume and rate and types of cement leakage between the two groups (P ＞ 0.05).None in targeted PVP group showed insufficient cement distribution in fractured area,while 16 cases (12.7％) in conventional PVP group (P ＜ 0.05).No significant differences in preoperative VAS of back pain existed among targeted PVP group,sufficient subgroup and insufficient subgroup (P ＞ 0.05).VAS of back pain was significantly decreased after PVP in three groups (P ＜ 0.05).Difference in postoperative VAS of back pain between targeted PVP group and sufficient filled subgroup was insignificant (P ＞0.05).However,postoperative VAS of back pain in insufficient filled subgroup was significantly increased compared with targeted PVP group and sufficient filled subgroup (P ＜ 0.05).Conclusion Targeted PVP provides sufficient cement to fill the fractured area and decreases incidence of unsatisfactory clinical outcome compared with traditional PVP,indicating a secure and effective new technique in the treatment of OVCFs.

OBJECTIVESTo isolate the cardiogenic fraction, which can enhance cardiogenic differentiation of bone marrow-derived mesenchymal stem cells (MSC) from Geum japonicum. The therapeutic effect of the isolated cardiogenic fraction was further tested in a rat myocardial infarction (MI) model.

METHODBioassay guided fractionation method was used for the isolation of the cardiogenic fraction, named as heart repair fraction (HRF). MI was induced by a permanent ligation of left anterior descending coronary artery. The rats exhibiting similarly decreased values of left ventricle ejection fraction (LVEF) and fraction shortening (LVFS) were used. The rats in test group (n = 10) were subject to HRF treatment (20 mg×kg(-1)×d(-1)) through gastric gavage daily for 4 weeks. Water alone (2 ml/d) was given through gastric gavage to rats in the control group (n = 10). The cardiac function was assessed by echocardiography at different time points. Masson trichrome staining was used for evaluation of the infarct size. Morphological and immunohistochemical studies were performed to investigate the HRF mediated myocardial regeneration.

RESULTSLVEF (66.2% ± 6.9%) and LVFS (46.8% ± 5.8%) were significantly increased two weeks post HRF treatment compared with the values (LVEF: 55.7% ± 6.0% and LVFS: 36.4% ± 5.2%) in control rats (all P < 0.01). The improved heart function was further restored 4 weeks post HRF treatment (P < 0.01). Furthermore, the treatment of acute MI with this HRF significantly reduced the infarct size (19.0% ± 6.1%) compared with that (31.1% ± 8.6%) in control rats (P < 0.01). Substantial regeneration of cardiomyocytes in infarcted region of the HRF treated heart was also observed that replaced a considerable part of the infarcted heart tissues resulting in remarkable reduction of the infarct size.

CONCLUSIONThe properties of this HRF isolated from Geum japonicum in stimulating substantial regeneration of myocardium in infarct region with consequently improved cardiac function appear to be new and represent a new approach for the treatment of MI.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Geum ; chemistry ; Male ; Myocardial Infarction ; drug therapy ; Myocytes, Cardiac ; drug effects ; Rats ; Rats, Sprague-Dawley ; Regeneration

OBJECTIVETo explore the effect of a non-lethal heat shock, in comparison with the treatment of interferon-gamma (IFN gamma), on the expression of major histocompatibility complex transactivator (CTA) and its downstream target gene of the human leukocyte antigens (HLA)-DR in Jurkat cells.

METHODSThe changes of CTA mRNA in Jurkat cells before and after the treatment of heat shock or IFN gamma were detected using real time RT-PCR. The changes of CTA protein were detected with Western blot. The expression of HLA-DR was detected with flow cytometry. : CTA mRNA and protein were induced in Jurkat cells under heat shock, but not with IFN-gamma. The expression of HLA-DR gene significantly increased after recovery (P<0.01).

CONCLUSIONThe expressions of CTA and HLA-DR in Jurkat cells remarkably increase after heat shock, indicating that heat shock may help reconstruct relevant genes in cells with immunologic gene deficiencies.

HLA-DR Antigens ; metabolism ; Heat-Shock Response ; physiology ; Humans ; Jurkat Cells ; Nuclear Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; Trans-Activators ; genetics ; metabolism

Objective To observe the effects of three pretreatments of electroacupuncture with different waveforms for septic brain injury in rats, and to explore the optimal waveform. Methods Eighty male Sprague-Dawley rats were divided randomly into five groups (n = 16):sham group,cecal ligation and puncture group (group CLP),continuous wave group (group CW),dilata-tional wave group (group DW)and intermittent wave group (group IW).A rat sepsis model was pre-pared by cecal ligation and puncture.Brain water content was detected.Tumor necrosis factor (TNF)-α,interleukin(IL)-6,malondialdehyde (MDA)and superoxide dismutase (SOD)in serum and frontal cortex were detected 48 h after sham or CLP operation.Pathological changes of frontal cortex,ex-pression of Toll-like receptor-4 (TLR4),and apoptosis of nerve cells were observed by hematoxylin and eosin staining (H&E),immunohistochemistry and TUNEL assay,respectively.Results Com-pared with the sham group,encephaledema,as well as brain injury and neuron apoptosis increased in group CLP (P <0.05).Concentrations of tumor necrosis factor-α,interleukin-6,and malondialdehyde in serum and frontal cortex significantly increased,and the activities of superoxide dismutase significantly de-creased (P < 0.05 ).The expression of TLR4 significantly increased (P < 0.05 ).Compared with group CLP,the aforementioned indicators in the continuous,dilatational,and intermittent wave groups significantly improved (P < 0.05 ).Compared among the electroacupunctured groups,the effect of dilatational wave was the most significant,followed by intermittent wave,and continuous wave was the least one (P <0.05).Conclusion EA pretreatment with different waveforms at Baihui and Tsusanli acupoints could reduce the septic brain injury,and DW might be the best one.The mechanism might be related with the inhibition of inflammation and oxidative stress response and the decrease in nerve cell apoptosis.

Background/Aims: Recently, the treatment of Crohn’s disease (CD) has changed to a treat-totarget strategy, in which disease progression is prevented with early intervention. We analyzed the long-term evolution of nonstricturing, nonpenetrating (B1) disease at diagnosis and factors related to disease evolution in pediatric CD. Methods: We retrospectively analyzed 402 patients between 2000 and 2013 who were younger than 18 years and had B1 disease at CD diagnosis. The median follow-up was 6.1 years (range, 1 to 13 years). The cumulative probabilities of developing stricturing (B2) or penetrating (B3) disease and associations between risk factors and disease behavior evolution were evaluated. Results: Among the 402 patients, 75 (18.7%) had B2 or B3 disease by the final follow-up. The cumulative probabilities of disease behavior evolution were 18.3%, 34.3%, and 50.9% at 5, 10, and 13 years, respectively. Patients whose disease progressed had an increased risk of intestinal resection (hazard ratio [HR], 3.61; 95% confidence interval [CI], 2.25 to 6.03; p<0.001). Firstdegree family history of inflammatory bowel disease (HR, 2.38; 95% CI, 1.07 to 5.28; p=0.032), isolated ileal involvement at diagnosis (HR, 7.55; 95% CI, 1.04 to 15.57; p=0.045), and positive anti-Saccharomyces cerevisiae antibody titers (HR, 2.10; 95% CI, 1.03 to 4.25; p=0.040) were associated with disease behavior evolution. Early treatment with biologics significantly reduced disease progression (HR, 0.46; 95% CI, 0.79 to 3.39; p=0.042). Conclusions This study suggests that early aggressive therapy should be considered in B1 behavior pediatric CD patients with risk factors of disease evolution to improve long-term outcomes

OBJECTIVETo observe the specific cellular and humoral immune responses after immunization with recombinant adenovirus Ad5F35-LMP2 in rhesus monkeys.

METHODSSixteen rhesuses were immunized with Ad5F35-LMP2 through intra-muscular injection in three groups: high dosage group (1.5 x 10(10) TCID(50)/rhesus), medium dosage group (1.5 x 10(9)TCID(50)/rhesus), low dosage group (1.5 x 10(8)TCID50/rhesus) and the last group was control (PBS 4 ml/rhesus). They were totally immunized three times at intervals of one month. The EBV-LMP2 specific cellular immune responses were tested during the 0, 4, 8, 12 weeks by Elispot after immunization respectively. And the titers of anti-LMP2 antibody were tested by EIA at the same time.

RESULTSEBV-LMP2 specific cellular and humoral immune responses which were induced by recombinant adenovirus Ad5F35-LMP2 can be found in all the three dosage groups. The potency of immune responses was related with the dosage of immunization. Higher dosage elicited more potent immune response.

CONCLUSIONThe recombinant adenovirus Ad5F35-LMP2 could elicit LMP2 specific cellular and humoral immune responses in rhesus.

Adenoviruses, Human ; genetics ; Animals ; Cell Differentiation ; Herpesvirus 4, Human ; genetics ; Immunity, Cellular ; immunology ; Immunization ; methods ; Macaca mulatta ; Recombinant Fusion Proteins ; genetics ; immunology ; Viral Matrix Proteins ; genetics ; immunology

OBJECTIVETo study the role of a BTB/POZ domain protein in the expression of hsp90alpha gene.

METHODSThe eukaryotic expression plasmids of sense- and antisense-GAGA related protein (GRP) or empty vector were transfected into Jurkat cells with pREP4 episomal vector plasmids carrying the hsp90alpha promoter sequence from -1756 to +37 and control plasmids pMCAT. Total RNA was extracted. The relative promoter activity of hsp90alpha-CAT reporter gene was determined by competitive RT-PCR assay.

RESULTSGRP markly increased the relative promoter activity of hsp90alpha-CAT reporter gene during heat shock.

CONCLUSIONGRP may promote the expression of hsp90alpha gene by participating in chromatin remolding.

Amino Acid Motifs ; Animals ; Checkpoint Kinase 1 ; Cloning, Molecular ; DNA ; metabolism ; DNA, Complementary ; metabolism ; DNA-Binding Proteins ; metabolism ; Drosophila ; genetics ; Drosophila Proteins ; genetics ; Gene Expression Regulation ; HSP90 Heat-Shock Proteins ; biosynthesis ; genetics ; Heat-Shock Response ; genetics ; Homeodomain Proteins ; chemistry ; genetics ; metabolism ; Humans ; Repressor Proteins ; genetics ; Transcription Factors ; genetics ; Two-Hybrid System Techniques

Previous studies indicated that B7-H4, the youngest B7 family, negatively regulates T cell-mediated immunity and is significantly overexpressed in many human tumors. Tumor stem cells are purported to play a role in tumor renewal and resistance to radiation and chemotherapy. However, the link between B7-H4 and tumor stem cells is unclear. In this study, we investigated B7-H4 expression in the medium of human glioma U251 cell cultures. Immunofluorescence results showed that U251 cells cultured in serum-free medium (supplemented with 2% B27, 20 ng/mL epidermal growth factor, 20 ng/mL basic fibroblast growth factor) maintained stem-like cell characteristics, including expression of stem cell marker CD133 and the neural progenitor cell markers nestin and SOX2. In contrast, U251 cells cultured in serum-containing medium highly expressed differentiation marker glial fibrillary acidic protein. Flow cytometry analysis showed serum-free medium-cultured U251 cells expressed higher intracellular B7-H4 than serum-containing medium-cultured U251 cells (24%-35% vs. 8%-11%, P < 0.001). Immunofluorescence in purified monocytes from normal human peripheral blood mononuclear cells revealed moderate expression of B7-H4 after stimulation with conditioned medium from U251 cells cultured in serum-containing medium. Moreover, conditioned medium from U251 stem-like cells had a significant stimulation effect on B7-H4 expression compared with serum-containing conditioned medium (P < 0.01). Negative costimulatory molecule B7-H4 was preferentially expressed in U251 stem-like cells, and conditioned medium from these cells more effectively induced monocytes to express B7-H4 than conditioned medium from U251 cells cultured in the presence of serum. Our results show that U251 stem-like cells may play a more crucial role in tumor immunoloregulation with high expression of B7-H4.
AC133 Antigen ; Antigens, CD ; metabolism ; Brain Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cells, Cultured ; Culture Media, Conditioned ; Culture Media, Serum-Free ; Gene Expression Regulation, Neoplastic ; Glial Fibrillary Acidic Protein ; metabolism ; Glioma ; metabolism ; pathology ; Glycoproteins ; metabolism ; Humans ; Monocytes ; cytology ; metabolism ; Neoplastic Stem Cells ; metabolism ; pathology ; Nestin ; metabolism ; Peptides ; metabolism ; SOXB1 Transcription Factors ; metabolism ; V-Set Domain-Containing T-Cell Activation Inhibitor 1 ; metabolism

OBJECTIVETo examine vibrio cholera (V.C) in aquatic products of littoral area, Zhejiang Province and to provide scientific evidence for administration of aquatic products and cholera epidemic control.

METHODSAll 990 samples of aquatic products collected from local markets, eateries and aquafarms in three chosen areas. Samples were proliferated in alkaline liquid medium, and purified in NO: 4 medium, the isolations were identified biochemically, and phenotype of strains were defined by phagocyte and coagulation with V.C. diagnostic serum. Three virulence genes (ctx, ace, zct) of the isolated strains were detected by polymerase chain reaction (PCR).

RESULTSThere were 1.41% samples caught by V.C., having a carrying rate highest in turtles of 8.9%. 14 strains were defined as three serogroups, and the numbers of Inaba, Ogawa, and Hikojima types were 2, 2, 10 respectively. Virulence genes had detected in 9 of 12 stains. All genes were detected in 5 strains, only ZOT genes in 3 strains, and both CTX and ACE genes in 1 strain.

CONCLUSIONSAquatic products from inshore in Zhejiang Province caught with V.C. strains might be divided into three serogroups. Most of them should be virulence genes. Cholera epidemic outbreak might be caused by those contaminated products.

China ; Food Microbiology ; Genes, Bacterial ; Seafood ; microbiology ; Vibrio cholerae ; genetics ; isolation & purification ; Virulence Factors ; genetics