In the present study, a new compound named 17-(6-cinnamamido-hexylamino-)-17-demethoxygeldanamycin (CDG) was obtained by introducing the cinnamic acid (CA) group into the 17-site of geldanamycin (GDM). The anti-cancer effects of CDG in vitro and in vivo were evaluated. MTT assay was used to examine the inhibitory effect of CDG on the proliferation of MCF-7, HepG2, H460 and SW1990 cells. Immunofluorescent staining flow cytometry combined with Annexin V-FITC/PI staining were used to detect apoptotic cells. Transwell assay was used to analyze the effect of CDG on cell invasion and migration ability. Western blotting was used to detect the expression levels of RAF-1, EGFR, AKT, CDK4 and HER-2 of MCF-7, HepG2 and H460 cells. The toxicities of CDG and GDM were evaluated in mice. Using the subcutaneously transplanted MCF-7 xenograft in nude mice, inhibitory effect was evaluated in vivo. The results showed that CDG inhibited the proliferation of cancer cells (IC50: 13.6-67.4 microg.mL-1). After exposure to CDG for 48 h, most cells presented typical morphologic changes of apoptosis such as chromatin condensation or shrunken nucleus. The rates of apoptosis of MCF-7, HepG2, H460 and SW1990 cells incubated with 10 microg.mL-1 CDG were 23.16%, 27.55%, 22.21%, 20.47%, respectively. A dose-dependent reduction of migration of four cell lines was found after exposure to CDG. The decreased levels of RAF-1, EGFR, AKT, CDK4 and HER-2 showed that CDG possessed HSP90 inhibitory effect. The result of animal toxicity test on the mice suggested that CDG had lower toxicity than GDM. Meanwhile, CDG inhibited the growth of MCF-7 xenografts of athymic mice.

Objective To investigate the expression of aquaporins 4 (AQP4) and histopathological changes in early phase of traumatic brain edema and the correlation between AQP4 expression and structural damage to blood-brain barrier (BBB).Methods A total of 120 healthy adult Wistar rats were divided into sham operation group and brain trauma group (which was subgrouped at hours 1,3,6,12 and 24 postinjury) according to random number table,with 20 rats per group.At each time point,brain water content was measured; brain edema and BBB structural changes were observed pathologically;IgG and AQP4 expressions in traumatic brain tissues were detected with immunohistochemical method and Western-blotting.Results In sham operation group,negatively stained IgG was observed and there were no abnormalities in brain tissue structure,brain water content as well as AQP4 expression.In brain trauma group,cerebral water content presented notable increase at 6 hours postinjury and peaked at 24hours; IgG expression showed significant increase at 1 hour postinjury,peaked at 6 hours postinjury and remained a high level at 24 hours.Pathologic observation revealed damage to BBB,blood red cells leaking out of the blood vessels,and tissue gap widening at 1 hour postinjury,which manifested as vasogenic brain edema.Further,those phenomena were gradually aggravated over time and became obvious at 6 hours postinjury.Intracellular edema occurred at 3 hours postinjury,with the presence of increased glial cell body,cytoplasm light staining or vacuolar degeneration,as well as mitochondria swelling and was also aggravated with time,particularly at 6 hours postinjury.Except that the previously mentioned two forms of edema coexisted at 12 hours postinjury,tissue necrosis,inflammatory cell infiltration and microglia proliferation were emerged and aggravated at 24 hours postinjury.AQP4 level decreased at 1 hour,minimized at 6 hours and regained at 12 hours,showing a V-shape curve.Conclusions Vasogenic edema characterized by BBB disruption is the primary histopathological change in early-phase of brain trauma,followed by the coexistence with intracellular edema and aggravation of the two forms of edema over time.AQP4 expression is down-regulated in the vasogenic edema phase but highly expressed at phase of the intracellular edema.

Hyperthermia is a means of adjuvant therapy, which have a sensitizing effect to radiotherapy and chemotherapy. In recent years, the molecular biology, cell and animal experimental research of tumor thermochemotherapy progressed very quickly, which provide theoretical foundation and guidance for us to further develop hyperthermia combined with chemotherapy in clinical trials. In this paper, the studies with the mechanism of thermo-chemotherapy treatment of tumor, different ways of thermochemotherapy and commonly used drugs in thermochemotherapy are reviewed.

Objective To investigate the stress in the periodontal tissues using three-dimansional finite element method when Richtts Arch was used.Methods Three-dimensional finite element models of the lower left central incisor and first molar were set up by means of CT.Stress distribution in root,PDL and alveolar bone,and the tendency of the tooth movement were obtained by calculation under Richtts Arch.Results The value of the force at the left lower incisor was -0.34 Newton and the value of the force at the left lower molar was 0.65 Newton.The molar model revealed that the tensile stress concentration was at the mesial root cervix and the compressive stress was at the distal root cervix.The incisor model showed that the tensile stress was concentrated at the lingual cervix and the compressive stress was concentrated at the apical tip.The arch wire exerted intruding force,lingual force and the incisor tended to lingual movement and intruding movement.The molar had the tendency of lingual movement and distal tipping movement.Conclusion The anchorage molar will incline mesially when Richtts Arch is used in treatment of deep overbite,the additional torque must be used in the anchorage molar.

Objective To investigate the effects of colchicine on the proliferation and apoptosis of human Tenon's capsule fibroblasts (HTCFs) in vitro.Methods HTCFs were cultured in vitro,and the subcultured cells were identified.MTS assay was used to observe the inhibitory actions of colchicine on HTCFs at different concentrations.The apoptotic rates of the cells were detected by flow cytometry.The apoptosisrelated proteins,including PARP,Caspase-9,Caspase-3 and active-Caspase-3,were detected by Western blot.Results MTS assay showed that colchicine inhibited the proliferation of HTCFs in a dose-and time-dependent manner.Flow cytometry showed that colchicine induced a dose-dependent apoptosis of HTCFs for 48 hours,the apoptotic rates of 5 μmol · L-1,10 μmol · L-1 and 20 μmol · L-1 were (18.37 ±4.26)％,(33.80 ±5.02)％ and (52.00 ± 2.00)％,respectively,there were significant differences compared with the control (F =91.59,P ＜ 0.001).Western blot showed the activation of Caspase-3 and PARP followed by colchicine treatment.Conclusion Colchicine significantly inhibits the proliferation of HTCFs in vitro,and induced apoptosis,which may be associated with the activation of mitochondrial apoptotic pathways.

Objective To observe the effect of Danshen in the treatment of severe hand-foot-and-mouth disease and investigate its mechanism.Methods One hundred and forty cases of children with severe hand foot and mouth diseases who hospitalized the intensive care unit were enrolled in the study from February 2012 to July 2014.The children were randomly divided into a control group and an observation group,with 70 cases in each group.The control group was given antiviral to reduce the intracranial pressure and intravenous immunoglobulin and the observation group was given Danshen in addition to the control group.The levels of neuron specific enolase (NSE)、S-100βprotein、TNF-α and IL-6 were detected at admission and checked again seven days after treatment.The changes of the above indicators and the clinical curative effect were compared before and after therapy.Results The total effective rate of the control group and the observation group was 80.0% and 92.9% respectively,showing statistical significance(P<0.05). After treatment, observation group of serum NSE (9.42 ± 2.56μg/Lvs. 11.71 ± 3.21μg/L,t=2.159), S-100β (177.34 ± 87.28 ng/Lvs. 286.14 ± 159.69 ng/L, t=2.315), TNF-α (15.98 ± 4.35 ng/Lvs. 23.17 ± 4.80 ng/L, t=4.297), IL-6 (41.72 ± 6.64 ng/Lvs. 52.05 ± 9.33 ng/L,t=3.492) , the level of were lower than those in the control group(P<0.05 orP<0.01). In the observation group, serum. The fever clearance time、the disappearance time of rash and the hospitalization time in the observation group (3.55 ± 1.02 d vs.4.55 ± 1.09 d, 7.14 ± 1.04 d) were shorter than those in the control group (4.46 ± 0.97 d vs.5.88 ± 1.44 d, 8.68 ± 1.06 d;t=5.409, 6.161, 8.677 respectively, P<0.01).Conclusions On the basis of conventional therapy,Danshen can effectively alleviate the systemic inflammatory response in children with severe hand foot and mouth diseases, reduce brain damage and improve the clinical efficacy.

DEK protein's carboxy-terminal DNA-binding region(CBD)is a newly found DNA-binding domain of DEK,which contains several phosphorylation sites and has a close correlation with DEK protein's function in vivo and in vitro.Using prokaryotic expression system,the peptide of DEK protein's carboxy-terminal DNA-binding region(CDB)was expressed and purified.In detail,the CDB DNA fragment was constructed into pET-30a(+)vector,and E.coli BL21(DE3)competent cells were used as host cells.The fusion protein His-CBD was expressed by induction of IPTG and purified by Ni-NTA agarose.The result of SDS-PAGE showed that the molecular weight of the purified protein was about 10.7kDa.Electrophoretic mobility shift assay(EMSA)indicated that DEK-CDB prefered to bind to supercoiled form of DNA in vitro,it had similar character to the binding of whole length DEK protein with DNA.This suggested that the carboxy-terminal DNA-binding region of DEK protein might function on the binding of DEK protein to DNA partly.

Objective To investigate the effects of AGEs-RAGE on the apoptosis of GLUTag cells and explore the possiblc mechanism.Methods GLUTag cells treated with 0、100、200、300μg/ml of AGEs for 24h were examined for gene and protein expression of RAGE using RT-PCR and western blotting,respectively.GLUTag cells were randomly divided into four groups:control,200μg/ml AGEs,AGEs+siRNA-RAGE and AGEs+apocynin.The protein expression of p22phox、p47phox 、Bcl-2、Bax in the cells were detected with western blotting.The reactive oxygen species (ROS) levels were examined using 2'7'-dichlorodihydroflur-rescein diacetate (DCFH-DA) and the apoptosis of L cells were tested by AnnexinV-FITC/PI.Results AGEs increased thc cxpression of RAGE in a dose dependent manner.Treatment with AGEs induced a significant increase in the expression of p22phox,p47phoxand the activity of ROS,caused up-regulation of Bax and down-regulation of Bcl-2,which enhanced the apoptosis of GLUTag cells.Apocynin,the inhibitor of NADPH oxidase,prevented those responses and the effects caused by AGEs were abolished by inhibition of RAGE activity with siRNA.Conclusion AGEs positively regulate the exprcssion of NADPH oxidase-derived ROS and its down-steam signaling pathway p53/Bax by targeting RAGE,leading to the apoptosis of GLUTag cells.

Objective To introduce the experience of management of inverted papilloma in frontal sinus in hospital. Methods Six patients with inverted papilloma in frontal sinus treated between 1999 and 2006 were reported, with special emphasis on the clinical symptoms, surgical technique and prognosis. Results Among 6 patients with frontal sinus involvement, there were 5 males and 1 female, aged between 24 and 66 years. All 6 patients were managed with endoscopic resection and additional open approach (giabellar nasal keyhole approach). Follow-up ranged from 2 - 8 years. Five patients treated with this protocol remained disease free, and 1 patient died of tumor recurrence and malignant degeneration 16 years after the first surgical management of sinonasal inverted papilloma. Conclusions The appropriate management of inverted papilloma involving the frontal sinus is combined open/endoscopic approach. The tumor extended into the lateral, far superior, and anterior aspects of the frontal sinus is truly at the limits of current endoscopic instrumentation. In order to avoid recurrence, the tumor must be reseeted completely during the operation. Postoperative radiotherapy is not absolutely necessary.

Diabetic peripheral neuropathy (DPN), one of the most common chronic complications of diabetes, is characterized by allodynia, hyperalgesia and spontaneous pain. Chinese epidemiological studies have shown that at least 25% diabetic patients suffered from painful DPN, which compromises patients' daily functioning and becomes a major health care problem. Although the pathogenesis of painful DPN is not fully understood and current treatment options are very limited, research in the field has advanced our understanding on the mechanism of painful DPN in the past Decade of Pain Research and Control. This review will mainly focus on evaluation of current diabetic animal models, possible molecular pathways and available therapies, with an emphasis on roles of purinergic receptor and its signaling transduction pathways. Common therapies address one or two DPN symptoms, while others offer wider symptom control, presumably by targeting pathophysiological mechanisms of DPN. Purinergic receptor signaling transduction pathways might become potential targets for treatment for painful DPN.
Animals ; Diabetes Mellitus ; physiopathology ; Diabetic Neuropathies ; physiopathology ; Humans ; Hyperalgesia ; physiopathology ; Pain ; physiopathology ; Receptors, Purinergic P2X ; physiology