OBJECTIVE:To study the influence of calcineurin gene polymorphism on the efficacy of cyclosporine A (CsA). METHODS:The blood samples of patients treated with CsA were collected. The trough blood concentration of CsA was detected by EMIT. The genotype of PPP3CA and PPP3CB was assayed by RFLP-PCR method. The expression of NFAT-regulated gene IL-2, IFN-γand GM-CSF were measured by RT-qPCR,which were used to define the index of indirect efficacy of CsA. The relationship of gene polymorphism with CsA efficacy was study by relationship analysis and multiple factor regression method,etc. RESULTS:A to-tal of 100 blood samples were collected. There was no significant correlation between the expression of CsA efficacy-related NFAT-reg-ulated gene GM-CSF and trough concentration of CsA(rGM-CSF=-0.04,P=0.238);the expression of IL-2 and IFN-γ were negatively correlated with trough concentration of CsA significantly(rIL-2=-0.384 3,P<0.001;rIFN-γ=-0.335 4,P<0.001). Using the average value of mRNA expression of IL-2 and IFN-γas indirect efficacy index,the polymorphism of PPP3CB rs3763679 site significantly in-fluenced the efficacy of CsA(P<0.05),but PPP3CA rs3804358 had no any effect on it(P>0.05). Stratified analysis showed that among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 genovariation(TC+TT) were better than those with wild-type gene (CC)(P<0.05). After the efficacy was normalized by CsA trough concentration, multivariate analysis showed that normalized efficacy of CsA was negatively correlated with gender,PPP3CB rs3763679,lactate dehy-drogenase and creatinine significantly,but positively correlated with PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate,etc. CONCLUSIONS:PPP3CB rs3763679 gene polymorphism influence the efficacy of CsA;among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 TT+TC is better than that of CC type. At the same time,gender,PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate and other factors all can influence the nor-malized efficacy of CsA to different extent. Multiple factors should be considered when using CsA.

Aim: Synthesized N-acylated chitosan(NAC) was used to anchor on the surface of plain docetaxel li-posomes( PDL) in order to to sustain drug release. Methods; NAC of low substitution degrees were prepared using hexanoic(C_6), lauric( C_(12)), and palmitic( C_(16)) anhydrides. W-palmitoyl chitosan was chosen to anchor the do-cetaxel liposomes. In vitro release profiles of conventional liposmes and the anchored liposomes was compared. Results: Hexanoic(C_6), lauric( C_(12)), and palmitic( C_(16)) -branched chitosans were synthesized. It was found that N-acylated chitosan-anchored DXL liposomes (NDL) increase stabilities of docetaxel liposomes. 70% of docetaxel was released from PDL in 24 hours but 39% from NDL Conclusion: Liposomes anchored by the low substituted N-acylated chitosan could decrease the drug release.

Objective To investigate the cell compatibility of polystyrene(PS) plate chemically modified with RGD peptides.Methods PS surfaces were carboxylated by permanganate oxidation in diluted sulfuric acid,and carboxyls were activated with water-soluble carbodiimide to graft with gelatin,collagen and RGD peptides.IR,X-ray photo-electronic spectroscopy (XPS) and dynamic contact angle were used to characterize the surface modification of PS surface.Results XPS results confirmed the existence of nitrogen element from protein molecules and the covalently binding of proteins to PS surfaces.Dynamic contact angle measurement indicated hydrophilicity of PS surfaces was improved obviously after grafting modification.The cell culture results showed that the cell adhesion and proliferation was better on modified surfaces than the initial.Conclusion The cell compatibility of PS surface was great improved after modification with RGD peptides,which would provide a potential strategy to improve the culture of purified endothelial progenitor cells isolated by immunomagnetic beads.

Objective To evaluate the efficacy of the treatment of hilar biliary malignant obstruc tion with multiple stent drainage.Methods One hundred and twenty-seven patients with malignant biliary hilar obstruction were enrolled.The obstructions at the common hepatic duct within less than 1 cm to the junction of the left and the right hepatic duct were found in 66 cases,at the proximal common hepatic duct and the left and the right hepatic ducts in 45 cases,at the right hepatic duct in 5 cases and at the both left and right hepatic duets in 11 cases.Sixty-six patients received stent placement through the right biliary ducts and the common bile duct by puncturing the right mid-axillary line.The other 37 patients received 2 stents placement (disposed"Y"style) through the left and the right hepatic duct punc turing routway.Seven patients received 2 stents placement (disposed"┌"style) through the right hepatic duct and the common bile duct with a stent placed between the left and the right hepatic duct.Three patients had right hepatic duct stent placed first,followed by right hepatic duct and common hepatic duct stent. Twelve patients had stents placed in the right hepatic duct with external drainage from the left hepatic duct. Two patients had multiple strictures at the right hepatic duct,who got multiple external drainages.The total serum bilirubin levels were measured pre-and post-operatively.Results One hundred and twenty-seven patients with bi[iary obstraction had internal stents placed for drainage.The average total bilirubin levels among 121 patients were (283.4?175.4 )?mol/L pre-operation and (63.2?11.8)?mol/L post-operation (P

Alanine Transaminase ; blood ; Animals ; Bilirubin ; blood ; Disease Models, Animal ; Endotoxemia ; etiology ; Endotoxins ; blood ; Gastrointestinal Hormones ; blood ; Gastrointestinal Motility ; physiology ; Intestine, Small ; physiopathology ; Liver ; pathology ; Liver Failure, Acute ; blood ; etiology ; physiopathology ; Liver Function Tests ; Rats ; Thioacetamide ; administration & dosage

OBJECTIVETo investigate the expression of 14-3-3 sigma and heat shock protein 27 (HSP27) in colorectal carcinoma(CRC) tissue and its clinical significance.

METHODSThe expression of 14-3-3 sigma and HSP27 was detected by immunohistochemical staining in 50 pathologically verified CRC cases. The association of clinical data with 14-3-3 sigma and HSP27 expression was examined.

RESULTSThe positive expression rate of 14-3-3 sigma was 10% in normal control mucosa and 58% in CRC tissue (P<0.01). The positive expression rate of HSP27 was 16% in normal control mucosa and 54% in CRC tissue (P<0.01). No correlation between 14-3-3 sigma and HSP27 expression was found in CRC tissue (P>0.05). The expression of 14-3-3 sigma was associated with patient age, tumor diameter and lymph node metastasis (LNM) (P<0.05), but not with gender, tumor differentiation or serous membrane invasion (P>0.05). The expression of HSP27 was associated with LNM (P<0.05), but not with gender, age, differentiation, tumor diameter or serous membrane invasion (P>0.05).

CONCLUSIONThe abnormal expression of 14-3-3 sigma and HSP27 is significantly associated with LNM in CRC.

14-3-3 Proteins ; Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Colorectal Neoplasms ; metabolism ; pathology ; Exonucleases ; metabolism ; Exoribonucleases ; Female ; HSP27 Heat-Shock Proteins ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Young Adult

OBJECTIVETo observe the role of Kupffer cells in the postburn production of TNFalpha, IL-1beta and IL-6 in severely scalded rats.

METHODS(1) The production of TNFalpha, IL-1beta and IL-6 from rat Kupffer cells stimulated by burn serum was observed. (2) The postburn change in the expression of cytokine mRNA from rat Kupffer cells was monitored. (3) The change in the plasma cytokine contents in scalded rats was determined after the application of gadolinium chloride, a specific inhibitor of Kupffer cells.

RESULTSKupffer cells could be stimulated by burn serum to release cytokines TNFalpha, IL-1beta and IL-6. The mRNA expression of TNFalpha, IL-1beta and IL-6 from rat Kupffer cells increased significantly after injury. But the postburn plasma levels of TNFalpha, IL-1beta and IL-6 decreased obviously to 34.71%, 36.99% and 33.7% of those in scalding group, respectively, after the Kupffer cell activity was inhibited.

CONCLUSIONThe plasma cytokines, i.e. TNFalpha, IL-1beta and IL-6, were primarily produced from Kupffer cells after injury in scalded rats, initiated by TNFalpha, IL-1beta and IL-6 mRNA transcription.

Animals ; Burns ; immunology ; metabolism ; Gadolinium ; pharmacology ; Interleukin-1 ; biosynthesis ; genetics ; Interleukin-6 ; biosynthesis ; genetics ; Kupffer Cells ; physiology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics

Mitochondrion is an organelle containing its own genome in eukaryotic cells , which encodes 37 genes involved in mitochondrial functions .Mitoepigenetic regulation is a major form of mitochondrial genome-encoded genes that regulates the expression levels without altering the sequences of the genes .The mitoepigenetic regulation is involved in the occurrence and development of various diseases .This paper reviews the progress of mitoepigenetic regulation and Alzhe-imer disease.

This study was aimed to investigate the expression characteristics of two transcriptional factors in Ikaros family, Ikaros and Helios isoforms and their mechanism, as well as their correlation with clinical parameters, which play important roles in transcriptional regulation of hematopoiesis. Expression of Ikaros and Helios isoforms in a total of 163 patients with leukemia and correlations between Ikaros and Helios isoforms were analyzed by PCR. The results showed that different expression patters of Ikaros and Helios isoforms existed in leukemia patients, that is, Ikaros isoform (Ik-6) was predominantly expressed in acute lymphoblastic leukemia (ALL) with BCR/ABL fusion gene, while Helios isoform (He-i) was overexpressed in T-cell ALL patients. The results of cloning and sequencing demonstrated that the isoforms of Ikaros and Helios had different genetic alterations. The statistical correlation between these two isoforms not was found in this study, although interaction between Ikaros and Helios has been reported. It is concluded that although Ikaros and Helios belong to the same family with similar structure of zinc fingers, their isoforms have different expression profile, specific genetic alterations, and different clinical relevance in patients with leukemia. The connection and interaction between Ik-6 and He-i needs further research.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Gene Expression Profiling ; Humans ; Ikaros Transcription Factor ; genetics ; metabolism ; Leukemia ; genetics ; metabolism ; Male ; Middle Aged ; Protein Isoforms ; genetics ; metabolism ; Young Adult

OBJECTIVETo investigate the relationship of protein kinase C-alpha (PKCalpha) expression/activation with tumor differentiation and resistance to chemotherapy drugs in superficial bladder carcinoma.

METHODSExpression of PKCalpha was measured by Western-blot analysis in 76 samples including tumor and normal tissues, respectively. A human RT4 bladder cancer cell line stably expressing green fluorescent protein (GFP)-PKCalpha (RT4/PKCalpha) was established. The sensitivity of the RT4/PKCalpha and parental cells to adriamycin (ADM) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The change of sensitivity of the RT4/PKCalpha to ADM were observed under the conditions of PKC activation and inhibition, respectively.

RESULTSTotal level of PKCalpha expression and the ratio of the amount of PKCalpha expression or PKC activity in membrane to that in cytosol (M/C) were all more higher in cancerous tissues than in normal tissues (P < 0.01); With the increase of tumor grade, the relative level of PKCalpha expression significantly increased in membrane (P < 0.01) and decreased in cytosol (P < 0.01), M/C of PKCalpha was significantly elevated (P < 0.01), and total relative level of PKCalpha expression significantly increased (P < 0.01). Thirty-eight cases recurred during the follow-up period in total seventy cases. Multivariate analysis showed that high M/C of PKCalpha was independent prognostic factor for tumor recurrence after standard ADM treatment in the 2-year follow-up (RR = 3.98, 95% CI 1.22-5.68, P = 0.03). Transfection of PKCalpha increased resistance of RT4 cells to ADM [resistance index (RI): 6.97, t = 3.24, P < 0.01]. PKCalpha activation further greatly promoted the resistance (RI: 148.11, t = 5.18, P < 0.001) while inhibition of PKCalpha did conversely (RI: 1.6, t = 1.29, P > 0.05).

CONCLUSIONThe abnormal activation and expression level of PKCalpha closely correlate with both tumor grade and intrinsic resistance to ADM in patients with superficial bladder carcinoma.

Aged ; Antibiotics, Antineoplastic ; pharmacology ; Carcinoma, Transitional Cell ; enzymology ; pathology ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; physiology ; Enzyme Activation ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Protein Kinase C-alpha ; metabolism ; Transfection ; Tumor Cells, Cultured ; Urinary Bladder Neoplasms ; enzymology ; pathology