Adolescent ; Adult ; Aged ; Female ; Humans ; Janus Kinase 2 ; genetics ; Karyotyping ; Male ; Middle Aged ; Mutation ; Myelodysplastic Syndromes ; genetics ; Nuclear Proteins ; genetics ; Proto-Oncogene Proteins c-kit ; genetics ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics

Recently, drug delivery materials have become the hotspot of medical study. Suitable delivery material plays an important role in constructing an excellent drug delivery system. Silk fibroin is a naturally occurring protein polymer with excellent biocompatibility, remarkable mechanical properties, biodegradability and outstanding processability. Due to its unique properties, silk fibroin has become a favorable carrier material for the incorporation and delivery of a range of therapeutic agents. Based on the structure and characteristics of silk fibroin, this article provides an overview of the recent research progress of silk fibroin used as drug delivery materials.
Biocompatible Materials ; Drug Delivery Systems ; Fibroins ; chemistry

A novel gene,located between dnrX and drrB in the genome of daunorubicin-producing strain Streptomyces coeruleorubidus SIPI-1482,was cloned and named as dauW.The full sequence of dauW was submitted to GenBank(Accession No.EF523565).Blast result indicated that it showed high homology with dnrW in GenBank.The exact function of dauW is as yet unknown despite the possibility that it might belong to a family of FAD-dependent oxidoreductases on the basis of conserved domain analysis.dauW was cloned into expression plasmids pET-28a(+)and pET-32a(+),respectively,and was successfully expressed in E.coli DE3 after induction with IPTG.The preliminary results of the expression of dauW suggested that it might be involved in the self resistance in Streptomyces coeruleorubidus due to the increased resistance to daunorubicin in the E.coli host.

TDP-4-ketohexulose reductase, encoded by dnmV, is important in daunorubicin biosynthesis. To obtain a daunorubicin block mutant, double cross-over plasmid pYG817 was constructed by inserting apramycin resistant gene and amplified dnmV together with upstream dnmU into vector pUC18. dnmV was successfully disrupted after transformation of daunorubicin-producing strain SIPI-1482 by pYG817. Daunorubicin was absent from metabolites of the resulting transformant, and its biosynthesis can be reconstituted by introducing dnmV expression plasmid into the disruptant, although the yield is lower than wild-type SIPI-1482, according to HPLC analysis. This mutant can be a good candidate for production of anthracycline such as epi-daunorubicin by introducing exogenous gene into the host.

TTI gene coding for Tsetse thrombin inhibitor was modified with E.coli bias codon and expressed in Escherichia coli with high efficiency.Recombinant protein was purified to more than 98% purity.Assay for enzyme activity determination was set up.The result showed that the fusion protein exhibited inhibiting activity for thrombin.Inhibitory rate of purified TTI was 73% when concentration of thrombin and substrate was 10U/ml and 250?mol/L respectively.Inhibition pattern was determined as competitive with Ki at 35?mol/L.

In-vitro assay methods were established to evaluate transactivation and binding activity of compounds on peroxisome proliferator-activated receptor y (PPARγ). Firstly, plasmids were constructed for transactivation assay of PPARγ response element (PPRE) triggered reporter gene expression, and for cell-based binding activity assay of the chimeric receptor, which was fused with PPARγ ligand binding domain (LBD) and yeast transcriptional activator Gal4. Secondly, by using PPARy competitive binding assay based on time resolved-fluorescence resonance energy transfer (TR-FRET), affinities of compounds and drugs to PPARγ were evaluated. In application of these above methods, the PPARγ activating potency and characteristics of different compounds were evaluated, and a novel benzeneselfonamide derivative, ZLJ01, was found to have comparable binding activity and affinity with the well-known PPARy agonist, but lack of PPRE mediated transactivation activity. In preliminary study on in-vitro hypoglycemic activity, ZLJ1 was found to promote insulin-stimulated glucose uptake by liver cells. Therefore, we believe that combining transactivation and binding activity as well as affinity evaluation, the system could be used to screen non-agonist PPARγ ligand as anovel PPARγ modulator
Genes, Reporter ; Hepatocytes ; Hypoglycemic Agents ; chemistry ; Ligands ; PPAR gamma ; agonists ; chemistry ; Plasmids ; Response Elements ; Sulfonamides ; chemistry ; Transcriptional Activation

This paper was to study the angiogenic inhibitory effect and the potential antitumor effect of the constructed recombinant DNA vaccine CRT/HPV6bE7 in vivo. The C57BL/6 mice were vaccinated respectively with recombinant CRT/HPV6bE7 DNA plamids. The inhibitory effects on angiogenesis of generated vaccines in vivo were evaluated by a bFGF-induced angiogenesis assay using the Matrigel kit. To investigate the potential antitumor effect, the mean tumor weights, sizes and tumor appearing times were measured in C57BL/6 mice treated with HPV6bE7-expressing B16 cells. The results indicated that the recombinants CRT180/HPV6bE7 and CRT180 showed strong anti-angiogenic effects in bFGF-induced angiogenesis in vivo. Moreover, CRT180/HPV6bE7 and CRT180 DNA vaccines could significantly inhibit the tumor growth in tumor challenge experiment, and CRT180/HPV6bE7 was superior to other vaccines in delaying tumor formation time, limiting tumor size and weight in tumor protection experiment. In conclusion, recombinant CRT180/HPV6bE7 DNA could elicit a most efficient anti-angiogenic effect and inhibit tumor growth in mice inoculated with DNA vaccines. The antiangiogenic activity of CRT were suggested residing in a domain between CRT 120-180 aa.
Animals ; Calreticulin ; genetics ; Female ; Human papillomavirus 6 ; immunology ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic ; prevention & control ; Oncogene Proteins, Viral ; genetics ; Papillomavirus Infections ; therapy ; Papillomavirus Vaccines ; immunology ; Recombinant Fusion Proteins ; genetics ; Vaccines, DNA ; immunology

Objective To investigate the clinical effect of endoscopic treatment of carpal tunnel syndrome (CTS) with subsynovial hyperplasia. Methods 37 cases (total 41 wrists) of CTS with subsynovial hyperplasia who accepted endoscopic treatment in our hospital were retrospectively analysised, all the transverse ligament of wrist were cutted off under endoscope and the hyperplastic subsynovial membrane arounding the superficial flexor tendon of finger. The changes of clinical symptoms and signs before and after operation were compared. Results According to Kelly classification, the overall excellent and good rate was 95.12%. After operation, the feel of numb and pain during night disappeared in all patients, the positive rate of Tinel and Phalen sign was both reduced to 2.44% (P < 0.05), and the mean value of two-point discrimination was reduced to (3.5 ± 0.9) mm. No serious complication occurred during treatment. Conclusion For the patients of CTS with subsynovial hyperplasia, to cut the transverse ligament tendon under endoscope and remove the subsynovial around the flexor tendon at the same time is a new and feasible surgical procedure with notable curative effect, which deserves clinical popularization.

OBJECTIVETo observe the effects of angiotensin II type 1 receptor blocker valsartan in preventing hepatic fibrosis induced by dimethylnitrosamine in rats.

METHODSExcept rats in the control group, all were given intraperitoneal injections of 1% dimethylnitrosamine (DMN 1 ml/kg, two or three consecutive days/a week for 6 weeks). From the first day of the intraperitoneal injection, rats in treatment groups were given valsartan for 8 weeks by gastric gavage. Liver tissue and blood samples of all rats were examined at 56 days (8 weeks). AngII levels were determined by radioimmunoassay. Hepatic mRNA levels of Collagen type I (Col I) and tissue inhibitor of metalloproteinase1 (TIMP1) were evaluated by reverse-transcription polymerase chain reaction (RT-PCR).

RESULTSValsartan significantly attenuated the degree of liver fibrosis and decreased the hepatic AngII content compared with DMN treated rats (P<0.01). mRNA levels of Col I and TIMP1 were upregulated in DMN treated rats compared with normal rats. Valsartan downregulated the elevation of Col I and TIMP1 mRNA levels (P<0.01).

CONCLUSIONHepatic AngII content of the model group was increased, the local tissue RAS was activated in DMN induced liver fibrosis. Valsartan can retard the progression of hepatic fibrosis and may provide an effective new strategy for anti-liver fibrosis therapy.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; therapeutic use ; Animals ; Dimethylnitrosamine ; Female ; Liver Cirrhosis, Experimental ; chemically induced ; prevention & control ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Tetrazoles ; pharmacology ; therapeutic use ; Valine ; analogs & derivatives ; pharmacology ; therapeutic use ; Valsartan

OBJECTIVEIn this report are reviewed two unrelated patients with typical normokalemic periodic paralysis (normoKPP) features and the results of screening the SCN4A gene for the disease-related mutation.

METHODSTwo sporadic cases with normoKPP were screened for previously known mutations in SCN4A gene (T704M, A1156T, M1360V, I1495F, M1592V) that lead to hyperKPP; denaturing high performance liquid chromatography (DHPLC) was used. Then the rest exons of SCN4A gene were screened by DHPLC, and sequence analysis was performed on those with DHPLC chromatogram variation when compared with unaffected control.

RESULTSTwo cases and one patient's father were detected with V781I, which was proved to be a singular missense mutation in SCN4A gene.

CONCLUSIONThe mutation V781I exists in Chinese patients with normoKPP and may be responsible for normoKPP.

Adult ; Amino Acid Sequence ; Base Sequence ; Child ; Chromatography, High Pressure Liquid ; methods ; DNA ; analysis ; genetics ; Exons ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation, Missense ; NAV1.4 Voltage-Gated Sodium Channel ; Paralyses, Familial Periodic ; genetics ; Point Mutation ; Sequence Analysis, DNA ; Sodium Channels ; genetics