2.Research progress of PoIo-Iike kinase 1 inhibitors targeting PoIo-box domain
Aihong YAO ; Yujie CHANG ; Cheng JIANG ; Haiying SUN
Journal of China Pharmaceutical University 2016;(1):1-8
The over-expression of Polo-like kinase 1(Plk1)is critical in the producing and progressing of multi-ple human tumors and is recognized as an effective target for the development of novel anti-cancer drugs.Currently a variety of small molecules targeting ATP or substrates binding sites have entered different stages of clinical trials.Polo-box domain(PBD)is a unique domain of Plks which plays an important role in the sub-cellular location of Plks and also in the recognition of their substrates,therefore it has become an attractive target for the development of novel target-directed Plk1 inhibitors.In this paper,PBD function of Plk1 was intro-duced,the progress of small molecule and phosphoserine /phosphothreonine contained short peptide Plk1 inhibi-tors targeting PBD was summarized.Further development of this kind of inhibitors was also proposed.
3.The analysis of clinical features of 140 cases with primary hyperparathyroidism
Xiao'ai YAO ; Hong CHANG ; Tao JIANG ; Lei XIU ; Zhen WEN
Chinese Journal of Clinical Oncology 2016;43(23):1035-1039
Objective:To compare the clinical characteristics in primary hyper(-) parathyroid hormone (PHPT) of the different patholog-ic types. Methods:Clinical data of 140 patients with PHPT proved by operation and pathology during January 2010 to June 2016 were retrospectively analyzed. Results:A total of 140 PHPT patients, including 13 (9.29%) cases of parathyroid carcinoma (PC), 27 (19.29%) cases of parathyroid hyperplasia (PH), and 100 (71.43%) cases of parathyroid adenoma (PA). The duration of the PC group was longer than the PH group and the duration of the parathyroid adenoma (PH) group was longer than the PA group (P<0.05). The percentage of young patients with PC was higher than in the other two groups (P=0.003). The diameters of the PC group were larger than those of the other two groups, and those of the PA group were larger than those of the PH groups (P<0.05). Blood calcium, parathyroid hor-mone (PTH), AKP, fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamete transpepti-dase (GGT), blood urine nitrogen (BUN), creatine (CRE), urinary calcium, and phosphorus of the PC group were higher than in the oth-er two groups (P<0.05). The blood calcium, PTH, alkaline phosphatase (AKP), urinary calcium of the PH group were lower than those in PA group (P<0.05). The proportion of ostalgia was 46.15%(6/13), 44.44%(12/27), and 49.00%(49/100). No statistical difference was observed (P>0.05). The postoperative calcium level of PC group was lowest (P<0.001), and the highest was of PTH (P<0.001). The pro-portions of clinical manifestation of the urinary system, digestive system, and nervous system in the PC group were 76.92%(10/13), 76.92%(10/13), and 15.38%(2/13), respectively, and these values were the highest in the three groups (P<0.05). The proportion of the clinical manifestation of the urinary system of the PH group was higher than that of the PA group. The fracture rate (30.77%, 4/13) and constipation rate (38.46%, 5/13) of the PC group were the highest among the three groups (P<0.05). Conclusion:The duration of patients with PC was the longest among the three groups. The percentage of young patients with PC was the highest. The abnormal parathyroid glands in the PC group were the heaviest. The PC group exhibited the lowest postoperative calcium level and the highest PTH level. The biochemistry and clinical manifestations of PC were obvious.
4.Chuanglingye-loaded collagen promotes chronic wound healing
Chang YAO ; Hong JIANG ; Yanlei XU ; Yongkang ZHU
Chinese Journal of Tissue Engineering Research 2015;(34):5518-5522
BACKGROUND:It has been shown thatChuanglingye has good anti-inflammatory effects, inhibits platelet aggregation and thrombus and improve wound healing. OBJECTIVE:To investigate the effects ofChuanglingye-loaded colagen on regulating inflammation and healing process of chronic wounds. METHODS: Forty rats were selected to make chronic wound models and randomly divided into four groups at 3 days after modeling: control group, colagen group,Chuanglingye group,Chuanglingye-loading colagen group, 10 rats in each group, respectively treated with 0.2 mL normal saline, 0.2 mL Chuanglingye, colagen and Chuanglingye-loaded colagen. The size of wounds was measured when modeling and at 3, 7 and 15 days after modeling. Amount of white blood cels, interleukin-6 level and tumor necrosis factor-α level in wound exudates were detected. The levels of hydroxyproline and matrix mentaloproteases (MMPs), including MMP-1, MMP-2, MMP-9, in the granulation tissue, were also detected. RESULTS AND CONCLUSION:At 3, 7, 15 days after modeling, the amount of white blood cels and levels of interleukin-6, tumor necrosis factor-α, MMP-1, MMP-2, MMP-9 were significantly lower in the Chuanglingye-loaded colagen group andChuanglingye group compared to the control group and colagen group (P < 0.01, P < 0.05). But there was no significant difference betweenChuanglingye-loaded colagen group and
Chuanglingye group. The level of hydroxyproline in the granulation tissue was significantly higher in the Chuanglingye-loaded colagen group than the other three groups at 3, 7, 15 days after modeling (P < 0.05), and the size of wound in theChuanglingye-loaded colagen group was significantly lower than that in the other three groups at 15 days after modeling (P < 0.01). In addition, no significant difference was found among the four groups at 15 days after modeling. These findings indicate thatChuanglingye-loaded colagen can significantly depress proliferation and infiltration of inflammatory cels on the wound surface, decrease levels of inflammatory factors and MMPs in wound exudates, and thus promote the healing of chronic wounds.
5.Reconstruction of complex proximal tibial defects using the long-stem tibial component combined with metallic wedge.
Xiang-dong YUN ; Li-ping AN ; Jin JIANG ; Chang-jiang YAO ; Hai-tao DONG ; Jia-xin JIN ; Ya-yi XIA
China Journal of Orthopaedics and Traumatology 2016;29(5):472-475
OBJECTIVETo investigate results of total knee arthroplasty using the long-stem tibial component combined with metallic wedge of knee prosthesis for the treatment of proximal defects.
METHODSFrom January 2011 to May 2013, 10 patients (11 knees) were treated with total knee arthroplasties using the long-stem tibial component with metallic tibial wedge of knee prosthesis. All the patients were female and the average age was 67 years old (ranged, 60 to 77 years old). All the patients were osteoarthritis. All the patients were classified as T2A style. The patients were evaluated according to knee score system (KSS).
RESULTSAll the patients were followed up for 12 months on average (ranged 3 to 29 months). The clinical outcome was assessed using KSS score, including knee pain score, knee stability score, knee range of motion score and knee walking score, knee stairs score. There were significantly differences at 6 weeks, 3 months, 6 months and 12 months between pre-and postoperative KSS score.
CONCLUSIONThe mechanical stability of tibial fixation in primary TKA is significantly increased by using the long-stem tibial component with metallic wedge of knee prosthesis, even in the presence of poor proximal bone.
Aged ; Arthroplasty, Replacement, Knee ; Female ; Humans ; Knee Joint ; physiopathology ; surgery ; Knee Prosthesis ; Male ; Osteoarthritis, Knee ; physiopathology ; surgery ; Range of Motion, Articular ; Tibia ; abnormalities ; physiopathology ; surgery
6.Crypotanshione reduces the expression of metadherin in DU145 prostate cancer cells.
Yi YAO ; Hui-zhang LI ; Ben-jiang QIAN ; Chang-ming LIU ; Jia-bin ZHANG ; Miao-chun LIN
National Journal of Andrology 2015;21(9):782-787
OBJECTIVETo investigate the effects of crypotanshinone (CPT) on the proliferation and apoptosis of DU145 prostate cancer cells as well as on the metadherin expression and the downstream PI3K/AKT signaling pathway in the DU145 cells.
METHODSWe treated DU145 prostate cancer cells with different concentrations of CPT for 24, 48, and 72 hours followed by evaluation of the proliferation and apoptosis of the cells by MTT assay and TUNEL, respectively. We determined the expressions of metadherin protein and mRNA in the DU145 cells by Western blot and RT-PCR respectively at different time points after CPT treatment. We also detected the expressions of the proteins metadherin, AKT, p-AKT, and Bcl-2 in the CPT-treated DU145 cells at 48 hours.
RESULTSCPT significantly inhibited the proliferation of the DU145 cells in a dose- and time-dependent manner (P < 0.05). After treatment with 10 µmol/L CPT for 24, 48, and 72 hours, the apoptosis rates of the DU145 cells were (29.42 ± 4.51), (55.07 ± 5.67) and (70.84 ± 4.66)%, respectively, significantly higher than (3.1 ± 2.48)% in the control group (P < 0.05). The expression of metadherin was remarkably downregulated at the transcription and translation levels (P < 0.05) and the expressions of the AKT signaling pathway and the Bcl-2 protein were markedly inhibited in the DU145 cells after treated with 10 µmol/L CPT for 48 hours (P < 0.05).
CONCLUSIONCPT can inhibit the proliferation and induce the apoptosis of DU145 prostate cancer cells, which may be associated with its suppression of the downstream PI3K/AKT signaling pathway by reducing the expression of metadherin in the DU145 cells.
Apoptosis ; drug effects ; Cell Adhesion Molecules ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Abietane ; pharmacology ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; Humans ; In Situ Nick-End Labeling ; Male ; Neoplasm Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects ; Time Factors
7.Expression of motilin in the hypothalamus and the effect of central erythromycin on gastric motility in diabetic rats.
Yun-Dan JIA ; Chang-Qin LIU ; Ming TANG ; Zheng-Yao JIANG
Neuroscience Bulletin 2007;23(2):75-82
OBJECTIVETo investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin (EM) on the regulation of gastric motility in diabetic rats.
METHODSThe motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals.
RESULTSDiabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus in the diabetic rats. Intracerebroventricular (i.c.v.) administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM (91.56 nmol, i.c.v.) dose-dependently increased the amplitude by (174.82 +/- 48.62)% (P<0.05), and increased the frequency by (70.43 +/- 27.11)% (P < 0.05) in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109.
CONCLUSIONMotilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.
Animals ; Diabetes Mellitus, Experimental ; metabolism ; Dose-Response Relationship, Drug ; Erythromycin ; administration & dosage ; pharmacology ; Gastrointestinal Agents ; administration & dosage ; pharmacology ; Gastrointestinal Motility ; drug effects ; physiology ; Hippocampus ; cytology ; metabolism ; Injections, Intraventricular ; Male ; Microinjections ; Motilin ; agonists ; metabolism ; Neurons ; cytology ; metabolism ; Paraventricular Hypothalamic Nucleus ; cytology ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Gastrointestinal Hormone ; agonists ; Receptors, Neuropeptide ; agonists ; Statistics, Nonparametric ; Supraoptic Nucleus ; cytology ; metabolism
8.Evaluation of autologous peripheral blood stem cell transplantation for diabetes combined with lower limb artery obturation using color Doppler ultrasound:Identical to results from angiography?
Fangping ZHOU ; Hongxian CHANG ; Xiusong YAO ; Jing CHEN ; Hui ZHANG ; Kun JIANG ; Hong SUN ; Jian LIU ; Yang SUI
Chinese Journal of Tissue Engineering Research 2010;14(14):2545-2548
BACKGROUND:Traditional therapeutic methods of diabetes combined with lower limb artery obturation showed poor outcomes such as drug or intervention.Stem cell transplantation is a new method to treat this disease in recant years,and has obtained good outcomes in the clinic.Evaluating the therapeutic outcomes of stem cell transplantation has great damage and cost much.Thus,color Doppler ultrasound is used to examine non-invasion in the artery of the lower extremity,which shows important clinical value.OBJECTIVE:To evaluate improvement of lower extremity artery lesion following autologous peripheral blood stem cell transplantation using color Doppler ultrasound,and to compare with results of angiography.METHODS:A total of 41 patients diagnosed as having diabetes combined with lower limb artery obturation were included.Following administration of recombinant human granulocyte-colony stimulating factor(rhG-CSF)(150 μg/d)for 5 days,peripheral blood mononuclear cells(PBMNCs)were mobilized and harvested by using a separator at day 5 to prepare stem cell suspension,and which were injected intramuscularly in the diseased extremities(3×109 per limb).The clinical and laboratory findings were monitored every week for 3 months to 1 year following stem cell transplantation.RESULTS AND CONCLUSION:After stem cell transplantation,severe pain lameness,local cool-feeling and ulcer were significantly improved,and ankle-brachial index was increased obviously(P<0.01).Color Doppler ultrasonography measurement showed that peak systolic velocity in diseased extremities was significantly increased post-transplantation(P<0.01).Following transplantation,blood flow of the lower limb arterial canal was improved to different extents;collateral vessels were increased surrounding obstructed artery and in muscles.Spiral CT for new collateral vessel formation were showed increased.No related complication or adverse effects were observed in 41 patients during observation.Results indicated that color Doppler ultrasound can exactly rapidly examine and assess blood transport improvement in the lower limbs following stem cell transplantation,which is identical to results from angiography.It also provides reliable evidences for the diagnosis on the transplantation of stem cells for the treatment of diabetes combined with lower limb artery obturation.
10.The influence of accelerated aging on color and microstructure of light-curing composite resin.
Jin-ying LIN ; Jiang-wu YAO ; Chang-jian LIN
West China Journal of Stomatology 2008;26(3):291-295
OBJECTIVEThe aim of this investigation was to examine the changes of the color stability, surface microstructure and chemical constitution of light-curing composite resin after accelerated aging, and the relations between them.
METHODSFour light-curing composite resin were aged in an accelerated aging instrument. The color was measured by CIE L*a*b* with a spectrophotometer after treatment for 24 h and 96 h. And the color differences were calculated. Environmental scanning electron microscopy (ESEM) and Fourier transform infrared spectroscopy (FTIR) spectrometer were used to examine the microstructure and chemical composition of the specimens before and after accelerated aging. The color differences were analyzed statistically by repeated-measures two-way analysis of variance and t-test after aging for 24 h and 96 h. The level of significance was defined as alpha=0.05.
RESULTSThe materials demonstrated statistically significant differences in color after aging between the 24 h and 96 h (P<0.05). There were significant influences on the microstructure and the chemical composition after aging. The matrix appeared some concaves and pores, the filler particles exposed after aging. The energy of chemical bonds were weaken or broken under the aging, and the unsaturated polymer reacted again.
CONCLUSIONThe color differences of the composite resin increase with the aging time and irradiation dose. The hybrid filled composites have the best color stability.
Color ; Composite Resins ; Curing Lights, Dental ; Dental Materials ; Humans ; Materials Testing ; Spectrophotometry