Interleukin-6(IL-6)is associated with cancer staging, survival, apoptosis and the sensitivity to chemotherapeutic drugs, and it is overexpressed in the cancer tissue and serum of cancer patient.IL-6 Can regulate proliferation and differentiation of cancer cells through IL-6/STAT3 signaling pathway. Therefore, blocking IL-6/STAT3 signaling pathway has potential therapeutic implications for cancer.

Background The malignant degree of the diffuse large B-cell lymphoma (DLBCL) is high.Radiation therapy is sensitive,but the therapeutic schedule can not be unified,reasonable and effective therapeutic schedule is important in clinic treatment of the DLBCL.Objective This study was to access the effect of X-ray on the cell cycle and cell apoptosis of the DLBCL.Methods DLBCL cell line was cultured and the cell suspension was inoculated to 12-well cultured plate.The cells exposed to X-ray for 6,12,24,48 hours with the irradiation doses of 2,4,6,8 Gy respectively.The cell proportions of different cycles were assayed by flow cytometer,and cell apoptosis index was evaluated and calculated.Non-irradiation cells served as controls.Results The cells grew well with a good cell vitality and round-like shape,and the growth was stable in generation 2 or 3.With the increase of X-ray doses and the lapse of irradiation time,the cell proportions in G0-G1 phase gradually reduced (Fdose =45.58,P=0.00; Ftime =43.11,P=0.00).However,cell proportions in G2-M phase were gradually increased as the increase of X-ray doses and lapse of irradiation time (Fdose =40.77,P =0.00 ; Ftime =91.91,P =0.00).In addition,the apoptotic proportion of the cells was significantly elevated with the increase of X-ray dose and irradiation time (Fdose =87.36,P =0.00; Ftime =37.31,P =0.00).Conclusions X-ray irradiation retards DLBCL in the G2-M phase and causes cell apoptosis in dose-and time-dependent manner.

Objective To study the effects of siltuximab on the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (Stat3) signaling pathway in ovarian epithelial carcinoma.Methods (1) Expressions of IL-6 in ovarian cancer patient specimens were assessed by immunohistochemistry.(2) Expression of phosphorylation Stat3 (pStat3) protein in siltuximab and IL-6 treated SKOV3 cell lines was determined by western blot, and expression levels of Stat3-induced bcl-XL,MCL-1, survivin, in siltuximab treated SKOV3/TR and CAOV3/TR cells lines were also determined by western blot.(3) Real-time image analysis was used to study the nuclear translocation of pEGFP-Stat3 fusion protein in ovarian cancer cell line SKOV3-pEGFP-Stat3 treated with siltuximab and IL-6.(4)Paclitaxel sensitivity in siltuximab treated SKOV3/TR and CAOV3/TR cell lines were assessed using the methyl thiazolyl tetrazolium (MTT).The 50% inhibiting concentration ( IC50 ) was defined as the paclitaxel concentration required to decrease the A490 value to 50%.Results ( 1 ) There were significantly difference in IL-6 staining density and the positive rate of IL-6 protein stained among the metastatic, and drug-resistant recurrent tumors,and matched primary tumors [69%(18/26)] vs.77% (20/26)vs.23% (6/26), P＜0.05].(2)A clear increase in Stat3 phosphorylation levels was observed in the IL-6-treated SKOV3 cell lines as compared to the SKOV3 cell lines.When the IL-6-treated SKOV3 cells were incubated with siltuximab with a range of concentrations of 0.001,0.01,0.1, 1.0 and 10 μg/ml, there were trends toward reduced pStat3 expression in the treated cell lines.Compared without treatment with siltuximab, the expression of the anti-apoptotic proteins MCL-1, bcl-XL and survivin in SKOV3/TR and CAOV3/TR cell lines were significantly decreased after treated with siltuximab.(3) In resting cells, the majority of pEGFPStat3 was cytoplasmic until the addition of human IL-6, which promptly induced the translocation of fluorescent Stat3 molecules to the nucleus.Exposure of cells to siltuximab with a range of concentrations of 0.001, 0.01,0.1, 1.0 and 10 μg/ml, followed by an incubation in IL-6 significantly reduced pEGFP-Stat3 nucleocytoplasmic translocation.(4) MTT cytotoxicity assay demonstrated that siltuximab increased paclitaxel-induced cell death and partially overcame paclitaxel resistance.Treated with siltuximab ( 1 and 10 μg/ml) ,the paclitaxel IC50 value of siltuximab in SKOV3/TR (0.49, 0.19 μg/ml) and CAOV3/TR (0.0010, 0.0008 μg/ml) cells were significantly lower than those in untreated cells (0.71,0.0021 μg/ml;all P ＜ 0.05).Conclusions These results demonstrated that siltuximab effectively block the IL-6 signaling pathways, which .Blockage of IL-6 signaling may provide benefits for the treatment of ovarian cancer.

Serine protease inhibitor (serpin) is a kind of serine protease activity regulator,which including nine subfamilies (SERPIN A ～ I).SERPINE (Serpin Peptidase Inhibitor,Clade E) can regulate many important life processes.In this paper,the physical and chemical properties,mechanisms and regulatory factors of SERPINE1 and SERPINE2 in the two important members of SERPINE family are introduced,and the research progress of SERPINE family in the fibrosis related diseases is described.

Objective To summarize the literature of autologous stem cell transplantation (ASCT) for the treatment of diabetic foot from 2004 to 2009 in China through analyzing its development, the main operative methods as well as the future development tendency. Methods Papers about breast reconstruction from 1987 to 2008 on Chinese Medical Current Content (CMCC) and Chinese Bio-medical Literature Database (CBMdisc) were metrologically analyzed according to journal, institute, operative method, time, content and so on. Results In all 105 papers collected, the first place in terms of journal, institute, author, area, operative method was as follows:Chinese Journal of Clinical Rehabilitation (6 papers), Beijing Capital Medical University (10 papers), Gu Yongquan (9 papers), Beijin (17 papers). Autologous bone marrow stem cell transplantation (ABMSCT) and autologous peripheral blood stem cell transplantation (APBSCT) are the main operative methods. Conclusions This paper provides a credible resource for further study through analyzing papers published in China on stem cell transplantation for treatment of diabetic foot in recent years. ABMSCT and APBSCT must be the main trends in the future. Before formulating strict indications, ABMSCT and APBSCT will be the main operation modes of ASCT. Quantifying indications of ASCT and coupling with other drugs in order to make better role of ASCT will be the main subject of the study.

Objective To investigate the clinical feature,diagnosis,treatment and prognosis of endometriosis of the bladder.Methods A retrospective study was conducted to review the clinical data of 10 patients with bladder endometriosis.Patient's age ranged from 30 to 48 years (with mean age of 38 years).Eight cases were admitted to hospital with urinary tract irritating symptoms during the menstrual period and 6 cases with hematuria; 2 patients without any symptoms were found through examination.The course of disease was 1-36 months (with mean of18 months).Ultrasound shows with low echo,single,wide base and no significant blood flow mass whose boundaries are less clear within the bladder wall.CT reveals soft-mass protruding into the bladder.Results Eight of the 10 patients were undergone partial cystectomy.And 2 cases was treated with transurethral resection.All cases were pathologically confirmed to be bladder endometriosis.Recurrence and ectopic lesion had not be found during follow-up period from 10 to 72 months (with mean of 30 ± 5.6 mon).Conclusions Endometriosis is a common disease in females in their reproductive years,but thebladder endometriosis is rare.The initial diagnosis needs to be made combining with imaging studies.It is confirmed by cystoscopy and pathological biopsy.Surgery is the option for the treatment of bladder endometriosis.

Objective To summarize the diagnosis and treatment strategy of the retroperitoneal fibrosis(RPF)associated with hydronephrosis.Methods The clinical data of 26 RPF cases treated from Jan.2005 to Mar.2012 were analyzed retrospectively.Early symptoms mainly included lumbar,flank,abdominal pain,nausea and vomit.Retroperitoneal mass was found in 12(46.2％)cases by ultrasonography,while in 23(88.5％)cases by CT.Results Ureterolysis with intra-peritoneal transposition was underwent in 10 cases who were followed up for 6-25 months,and no relapse was found.Ureterocystostomy was underwent in 1 cases for difficulty in ureterolysis who was followed up for 45 months,and no relapse was found.D-J stent inter-ureter drainage was performed in 15 cases,all of whom had replaced the D-J stent discontinuously except that 2 cases had ceased replacement successfully,and all of the obstruction were relieved during the follow-up period for 16-84 months post-operatively.Conclusions Retroperitoneal mass can be found by CT of abdomen effectively.The therapeutics should depend on the pathological condition of the retroperitoneal mass.Obstruction can be relieved effectively by both ureterolysis with intraperitoneal transposition and D-J stent inter-ureter drainage and replacement.The complication occurred in the replacement of D-J can be relieved or eliminated by all kinds of measures.The unimpaired kidney drainage should be paid attention in the follow-up.

In adult orbital diseases, thyroid associated ophthalmopathy (TAO) is of very high incidence rate, and it can seriously affect patients' appearance, eyesight and binocular visual function and so on, and significantly reduce the patients' quality of life.In addition to the common manifestations such as eyelid retraction, exophthalmos and strabismus, some TAO patients may suffer from obviously increased ocular pressure and even visual field damage, which are often ignored or missed in diagnosis and should be paid more attention to.The pathogenesis of elevated intraocular pressure in TAO is mainly related to the elevated episcleral venous pressure and the extraocular muscles.Because the elevated intraocular pressure resulted from TAO is secondary and its pathogenesis is complex, personalized treatment different from primary glaucoma therapy is needed.In this article, the epidemiology, pathogenesis and therapy of elevated intraocular pressure in TAO including medication, surgery, and radiotherapy were reviewed to provide reference for the clinical diagnosis and treatment for TAO.

Under natural environments, plants and algae have evolved various photosynthetic acclimation mechanisms in response to the constantly changing light conditions. The state transition and long-term response processes in photosynthetic acclimation involve remodeling and composition alteration of thylakoid membrane. A chloroplast protein kinase named Stt7/STN7 has been found to have pivotal roles in both state transition and long-term response. Here we report the crystal structures of the kinase domain of a putative Stt7/STN7 homolog from Micromonas sp. RCC299 (MsStt7d) in the apo form and in complex with various nucleotide substrates. MsStt7d adopts a canonical protein kinase fold and contains all the essential residues at the active site. A novel hairpin motif, found to be a conserved feature of the Stt7/STN7 family and indispensable for the kinase stability, interacts with the activation loop and fixes it in an active conformation. We have also demonstrated that MsStt7d is a dualspecifi city kinase that phosphorylates both Thr and Tyr residues. Moreover, preliminary in vitro data suggest that it might be capable of phosphorylating a consensus N-terminal pentapeptide of light-harvesting proteins Micromonas Lhcp4 and Arabidopsis Lhcb1 directly. The potential peptide/protein substrate binding site is predicted based on the location of a pseudo-substrate contributed by the adjacent molecule within the crystallographic dimer. The structural and biochemical data presented here provide a framework for an improved understanding on the role of Stt7/STN7 in photosynthetic acclimation.
Amino Acid Sequence ; Amino Acid Substitution ; Arabidopsis ; metabolism ; Arabidopsis Proteins ; chemistry ; genetics ; metabolism ; Binding Sites ; Catalytic Domain ; Chlorophyta ; enzymology ; Crystallography, X-Ray ; Cyclin-Dependent Kinase 2 ; chemistry ; metabolism ; Molecular Sequence Data ; Phosphorylation ; Protein Structure, Secondary ; Protein-Serine-Threonine Kinases ; chemistry ; genetics ; metabolism ; Sequence Alignment ; Substrate Specificity

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr²⁺. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABA_A receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Parvalbumins/metabolism* ; Corpus Striatum/metabolism* ; Interneurons/physiology* ; Neurons/metabolism* ; Neostriatum