SUMOylation is an important post-translational modification of proteins. Similar to ubiquitylation, SUMOylation is the process that the small ubiquitin-like modifier (SUMO) proteins are specifically and covalently binding to lysine residues of substrate proteins. Through SUMOylation, the physiological functions and pathological processes of cells are well controlled and balanced, and its abnormal activation has been reported in various tumors. Therefore, SUMOylation has been a potential target for anti-tumor drug development. In this review, we summarize recent advances on development of inhibitors targeting SUMOylation pathway and their antitumor properties.

AIM: The distribution of endothelin-1(ET-1) in uterine tube and its source were investigated in order to find out relation between endothelin-1 and function of uterine tube.METHODS: The distribution of endothelin-1 and the expression of ET-1 mRNA in the rabbits uterine tubes were studied using SABC immunohistochemistry and in situ hybridization histochemistry with digoxigenin-labelled rat ET-1 cRNA probe. RESULTS: ET-1 granules with red color were seen in the uterine tube epithelial cells and they were located mainly above the cell nucleus and under the cell surface membrane. Less ET-1 granules were seen in the myometrium of uterine tube. ET-1 mRNA positive hybridization signals with deep blue were distributed in the uterine tube epithelial cells. These signals were strong and dense. They were distributed mainly above the nucleus and near the cell surface membrane. ET-1 mRNA positive hybridization signal was not seen in the myometrium of uterine tube.CONCLUSION: Our results indicate that epithelial cells of rabbit's uterine tube epithelial cells secrete ET-1.

Objective To summarize the characteristics of fetal hand deformity in prenatal two-and three-dimensional u1trasonography. To analyze the causes of missed diagnosis of prenatal u1trasonography in detecting fetal hand deformity. Methods Systematic continuous sequence approach was performed with two-and three-dimensional u1trasonography in 11 854 cases to detect the fetal hand development, deformity and accompanied malformations. Prenatal sonographic features of fetal hand deformities (59 cases) were correlated with the morphology and X-ray characteristics of the delivered fetuses. Results Fifty-nine cases of fetal hand deformity were diagnosed out of 11 854 fetuses by prenatal u1trasonography:44 cases of abnormal wrist posture,1 case of full-ifnger absence, 2 cases of metacarpal and phalanx absence, 3 cases of clinodactyly, 2 cases of forearm and hand absence, 1 case of syndacty, 1 case of polydacty, 5 cases of lethal bone dysplasia. The detection rate was 0.50%(59/11 854). Eight cases were missed:3 cases of partial ifnger absence, 2 cases of clinodactyly, 1 case of syndacty, and 2 cases of polydacty. The rate of missed diagnosis is 11.90%(8/67). Abnormal wrist posture showed a hook-shaped hand in the wrist. Full-finger absence showed that one or multiple ifngers were absent. Metacarpal and phalanx absence showed no fetal hands. Clinodactyly showed that four ifngers were not in the same plane. Forearm and hand missing showed that ulna, metacarpal and phalangeal were absent. Syndacty showed a beak-like hand. Multi-ifnger indicated six ifngers in one hand. Lethal bone dysplasia showed very short limbs. Conclusions Prenatal u1trasonography played an important role in detecting and diagnosing severe type of fetal hand deformity. The detection rate of fetal hand deformities can be greatly improved by appropriate use of the scan-time, fetal position, systematic continuous sequence approach and real three-dimensional u1trasonography.

Acetates ; pharmacology ; Animals ; Disease Models, Animal ; Diving ; adverse effects ; Ear Canal ; injuries ; Nitrogen ; Oxygen ; Protective Agents ; pharmacology ; Rabbits

BACKGROUNDThere have been few studies to evaluate the effects of helical CT on bladder tumor. This study was to evaluate the clinical applications of helical CT dynamic contrast-enhanced axial imaging, multiplanar reformation (MPR), three-dimensional (3D) reconstruction and virtual cystoscopy (CTVC) in bladder tumors.

METHODSThe precontrast and four-phase postcontrast helical CT scans were performed in 42 patients with bladder tumors confirmed by conventional cystoscopy and pathology. MPR, 3D and CTVC images were generated from the volumetric data of the excretory phase. The results were then compared with the findings of conventional cystoscopy and surgery in a double-blinded mode.

RESULTSThe sensitivity of the axial, 3D and CTVC images in detecting the bladder tumors were 90.8%, 76.9% and 95.4% respectively. The dynamic contrast-enhanced axial images could provide excellent intramural and extravesical information, and the accuracy in preoperative tumor staging was 87.7%. MPR could directly demonstrate the origin and extravesical invasions of the tumors and their relation to the ureter. 3D and CTVC images were useful for displaying the surface morphology of the tumor and the relationship between the tumor and the ureteric orifices, whereas CTVC could depict the tumors smaller than 5 mm that were not seen on the axial images.

CONCLUSIONSThe combination of axial, MPR, 3D and CTVC images with helical CT can provide comprehensive information on bladder tumor.

Adult ; Aged ; Cystoscopy ; Female ; Humans ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Tomography, Spiral Computed ; methods ; Urinary Bladder Neoplasms ; diagnostic imaging

UNLABELLEDOBJECTIVE : To study the anti-atherosclerotic mechanism of bear bile powder (BBP) in Shexiang Tongxin Dripping Pill (STDP) , and to provide scientific evidence for treating atherosclerosis (AS) by its therapeutic characteristics of cool resuscitation.

METHODSAS model was duplicated using ApoE-/- gene knocked mice fed with high-fat diet. Thirty ApoE-/- deficient male mice were divided into four groups according to body weight using random digit table, i.e., the model group (A, n =9), the STDP group (B, n=E7), the STDP without BBP group (C, n =7), and the BBP group (D, n =9). Besides, another 9 C57BL/6J male mice of the same age were recruited as a normal control group (E). All mice in Group B, C, and D were respectively administered with corresponding drugs (30, 30, and 0. 33 mg/kg) by gastrogavage. Equal volume of normal saline was administered to mice in Group A and E. All medication lasted for 8 successive weeks. Serum levels of inflammatory cytokines such as interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor a (TNF-α), interferon y (IFNγ), and oxidized low-density lipoprotein (ox-LDL) were measured by ELISA. Serum levels of malondialdehyde (MDA), activities of glutathione (GSH) and superoxide dismutase (SOD) were determined using biochemical assay. Contents of reactive oxygen species (ROS) in the aortic root was detected by dihydroethidum (DHE) fluorescent probe. Expression levels of microRNAs (such as miR-20, miR-21, miR-126, and miR-155) were detected by real-time PCR.

RESULTSThe fluorescence intensity of the aorta was obviously enhanced in Group A. But it was obviously attenuated in Group B, C, and D, and the attenuation was the most in Group B. Compared with Group E, serum levels of IL-2, IL-6, TNF-α, IFN-γ, oxLDL, and MDA all increased (P <0. 01), GSH contents and SOD activities decreased (P <0. 01), expression levels of miR-126, miR-21, and miR-155 in aorta increased (P <0. 01), and the expression level of miR-20 decreased in Group A (P<0. 01). Compared with Group A, serum levels of IL-2, IL-6, TNF-α, IFN-γ, oxLDL, and MDA were all down-regulated (P <0. 01), GSH contents and SOD activities were up-regulated (P <0. 01), expression levels of miR-126, miR-21, and miR-155 in aorta were down-regulated in Group B, C, and D (P <0. 01). The expression level of miR20 was up-regulated in Group B and D (P <0. 01). Compared with Group B, serum levels of IL-2, IL-6, TNF-α, IFN-γ increased (P <0.01); GSH contents and SOD activities decreased, levels of MDA and oxLDL increased (P <0. 01) in Group C and D. Expression levels of miR-20 and miR-155 were down-regulated in Group C and D (P <0. 01).

CONCLUSIONSSTDP played roles in significantly regulating inflammatory factors and oxidative stress factors. Its mechanism might be possibly associated with regulating expressions of miR-126, miR-21, miR-155, and miR-20 in aorta. BBP played significant roles in STDP.

Animals ; Aorta ; Apolipoproteins E ; metabolism ; Atherosclerosis ; Bile ; Cytokines ; Diet, High-Fat ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Interleukin-6 ; metabolism ; Lipoproteins, LDL ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Plaque, Atherosclerotic ; drug therapy ; Reactive Oxygen Species ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Ursidae

OBJECTIVETo investigate the antifibrotic effect of the Chinese herbs Modified Danggui Buxue Decoction (, MDBD) on adraimycin-induced nephropathy in rats.

METHODSThirty-two male Sprague Dawley albino rats were randomly divided into 4 groups: the control, model, and two treatment groups, with 8 in each group. Nephropathy was induced in the latter 3 groups by intravenous injection of adriamycin. Rats in the two treatment groups received intragastric administration of benazepri (a positive control) or MDBD, which is composed of extracts of Radix Angelicae sinensis, Astragalus membranaceus (Fisch.) Bge and Rhizoma chuanxiong. Serum albumin, blood lipids, 24-h urine protein and urine N-acetyl-b-D-glucosaminidase (NAG) were measured every 2 weeks. The ratio of kidney to body weight was measured. The expressions of extracellular matrix proteins in the renal cortex, including colleagen IV (Col-IV) and fibronectin (FN), were examined by immunohistochemistry, and the transcription of genes encoding transforming growth factor β1 (TGF-β1), the tissue inhibitors of matrix metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 9 (MMP-9) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) at the end of the 8-week treatment.

RESULTSCompared with the untreated rats in the model group, MDBD significantly increased serum albumin, lowered the blood lipids and decreased the ratio of kidney to body weight. MDBD significantly reduced the excretion levels of urinary protein and NAG as well as the accumulation of extracellular matrix (ECM), including Col-IV and FN, in the renal cortex. Further, MDBD decreased TIMP-1 and TGF-β1 gene expressions and increased MMP-9 gene expression in the kidney.

CONCLUSIONSMDBD was effective in treating the rat model of nephropathy. The clinical benefit was associated with reduction of renal fibrosis. The antifibrotic effect of MDBD may be mediated through the regulation of TIMP-1, MMP and TGF-β1 gene expressions.

Acetylglucosaminidase ; urine ; Animals ; Body Weight ; drug effects ; Collagen Type IV ; metabolism ; Doxorubicin ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fibronectins ; metabolism ; Fibrosis ; Gene Expression Regulation ; drug effects ; Immunohistochemistry ; Kidney Cortex ; drug effects ; enzymology ; pathology ; physiopathology ; Kidney Diseases ; blood ; drug therapy ; physiopathology ; urine ; Kidney Function Tests ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Organ Size ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum Albumin ; metabolism ; Time Factors ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Triglycerides ; blood

OBJECTIVE: To clone vascular endothelial growth factor (VEGF) cDNA gene, construct its eukaryotic expression vector and to express this recombinant plasmid in COS-7 cells. METHODS: Human VEGF165 cDNA was amplified by RT PCR from human ovarian carcinoma. After DNA sequenced, the VEGF165 cDNA was inserted into eukaryotic expression vector pcDNA3.1(-). The recombinant plasmid pcDNA3.1 VEGF165 containing VEGF165 cDNA was identified by enzyme digestion and transferred into COS-7 cells mediated by liposome. The transient expression of VEGF was detected by immunohistochemical staining. RESULTS: The cloned VEGF165 cDNA was confirmed by enzyme digestion and DNA sequence analysis. The immunohistochemical results showed that the VEGF165 protein was expression in COS-7 cells 72 h after gene transfer. CONCLUSION: VEGF165 cDNA gene successfully cloned and expressed in COS-7 cells.

Objective To analyze the clinical features and to explore the potential mode of genetic transmission of vitiligo vulgaris in Chinese Han population. Methods Information on the clinical features and the familial history of patients with vitiligo vulgaris was collected by a uniform questionnaire. The data were inputted into a data base, then analyzed by Epi Info 5.0 and SPSS 10.0 software packages. A complex segregation analysis was conducted using the REGTL program in SAGE 3.1 package in order to propose the putative mode of genetic transmission for vitiligo vulgaris. Results The mean age of onset of vitiligo vulgaris of the males and females was about 19 years old. In the severity of the disease and the season of onset, there was no significant difference between males and females. For the patients with vitiligo vulgaris, there was a female preponderance of complicating with autoimmune disorders, especially hyperthyroidism. The prevalence rates of vitiligo in patients′ relatives were significantly higher than that in general population. The mode of transmission of vitiligo vulgaris was one of the multifactorial inheritance according to the results obtained by the complex segregation analysis. Conclusions There are no differences in the prevalence and the age of onset between males and females patients. There is a marked familial aggregation in the patients with vitiligo vulgaris. The familial clustering might result from the polygenic additive genetic background and common environmental factors. It is suggested that vitiligo vulgaris be a multifactorial complex disease.

OBJECTIVETo evaluate the diagnostic effect of helical CT on bladder tumor.

METHODSIn 28 patients with bladder tumors which had been confirmed by conventional fiberoptic cystoscopy (FC) and pathology, precontrast and four-phase postcontrast helical CT scans were performed with multiple plane reconstruction (MPR), three dimensional (3D) reconstruction and CT virtual cystoscopy (CTVC) images constructed from the volumetric data of the excretory phase. The results were then compared with the findings of conventional fiberoptic cystoscopy and surgery through a double-blind manner.

RESULTSThe sensitivity of the helical CT axial, 3D and CTVC images in detecting bladder tumor were 92.3%, 76.9% and 96.2% respectively. The accuracy in preoperative tumor staging of helical CT was 83.0%. The axial images could provide excellent intramural and extravesical information, and MPR could directly show the origin and extravesical invasion of the tumor and its relation to the ureter. 3D and CTVC images were useful in displaying the surface morphology of the tumor and its relation with the ureteric orifices, whereas CTVC images could depict a tumor smaller than 5 mm that could not be visualized on the axial images.

CONCLUSIONCombining interpretation of axial, MPR, 3D and CTVC images, helical CT is able to provide comprehensive information for the diagnosis and treatment of bladder tumor.

Adult ; Aged ; Female ; Humans ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Tomography, Spiral Computed ; Tomography, X-Ray Computed ; Urinary Bladder Neoplasms ; diagnostic imaging