Objective Insulin-like growth factor-1 receptor (IGF-1R),similar to insulin receptor,is one of the families of re- ceptor tyrosine kinases.,which has been found to be overexpressed in a variety of cancer.It is the main proliferation and survival sig- nal molecule in cancer cell and plays an important role in cancer growth and progress.Blocking signal transduction of IGF-1R by vari- ous strategies can suppress tumor growth and induce regression of established tumor.This study is to construct the siRNA expression vector targeting IGF-1R and to evaluate its ability to induce cell apoptosis in human lung cancer cells.Methods Two siRNA expres- sion vector,pENTR/U6-shRNA-1 and pENTR/U6-shRNA-2 targeting IGF-1R,were constructed using pENTR/U6 vector,and a vector targeting hieiferase gene,pENTR/U6-shRNA-Iuc,was constructed as control.After vectors were transfected into A549 for 48h, knockdown of IGF-1R mRNA and protein and Akt phosphorylation were accessed,and DNA ladder and flow cytometry were used for cell apoptosis.Results siRNA expression vectors targeting IGF-1R were successfully constructed,which was confirmed by PCR and DNA sequencing,pENTR/U6-shRNA-1 and pENTR/U6-shRNA-2 demonstrated the expression were (22.1?2.5) % and (80.1? 3.9) % in IGF-1R mRNA level,(15.2?3.1)% and (47.1?4.1)% in protein level,respectively,compared with pENTR/U6- shRNA-luc.Suppression of IGF-1R by pENTR/U6-shRNA-1 blunted Akt phosphorylation,increased cell apoptosis induced by 3% ethanol,and retained 77.5 % A549 cells in the G0/G1 phase.Conclusion siRNA expression vector targeting IGF-1R can effectively suppress the expression of IGF-1R expression in A549.This study suggests that DNA vector-based RNAi has the potential to be effec- tive and practical cancer gene therapy strategy.

Peptide cyclization, a pivotal approach to modifying linear precursors of proteins and pepticles, has been used to enhance their biological activities and serum stabilities. Recently, sortase A (SrtA) from Staphyloccus aureus becomes a promising new technology for efficiently incorporating site specific modifications into proteins, conjugating the cell surface and cyclizing the linear peptides. In this study, we constructed two recombinant expression systems, one with chitin binding domain and the other with six-histidine tag and chitin binding domain on the N-terminal of SrtA, separately. The results of enzymatic kinetics indicate that the two recombinant tags do not impair the transpeptidase activity of SrtA compared with the standard reaction reported under the same reaction condition. The two synthesized peptides with N-ternimal three glycines and C-terminal penta-amino acid motif, LPETG, were cyclized using immobilized and recycled SrtA. The SrtA-based cyclization promises to represent a simple method for easy and efficient enzymatic synthesis of large cyclic peptides.
Aminoacyltransferases ; metabolism ; Bacterial Proteins ; metabolism ; Cyclization ; Cysteine Endopeptidases ; metabolism ; Enzymes, Immobilized ; metabolism ; Kinetics ; Peptides ; metabolism ; Peptides, Cyclic ; biosynthesis ; Staphylococcus aureus ; enzymology

Objective To investigate the impact of prior cerebral infarction (PCI) on in-hospital mortality in patients with Acute Myocardial Infarction (AMI).MethodsA retrospective analysis of documents of a total of 3572 consecutive patients with AMI admitted to Xuanwu Hospital of Capital Medical University from 2002 Jan.1 to 2009 Dec.31 were performed.Results There were 564 patients ( 15.8% )with PCI.Compared with the group of without PC1,the group with PCI were substantially older[(69.4 ±9.9) vs (64.2 ± 12.9)years,P =0.000],and had a higher prevalence of hypertensive disease,diabetes mellitus,prior myocardial infarction (MI) and non-ST-segment elevation myocardial infarction(NSTEMI)( respectively,71.0% vs 57.3%; 41.0% vs 25.7%,12.9% vs 9.5%; 14.9% vs 10.7%,P ＜ 0.01 ),and a higher in-hospital mortality ( 16.5% vs 10.0%,P= 0.000).Univariate analysis demonstrated that in-hospital mortality associated with age,gender,extensive anterior MI,anterior MI,diabetes mellitus,prior cerebral infarction,prior myocardial infarction,coronary angiography and percutaneous coronary intervention.Logistic regression analysis found that risk factors were age,extensive anterior MI,anterior MI,diabetes mellitus and prior cerebral infarction,and protective factors were coronary angiography and percutanous coronary intervention.PCI was independently associated with in-hospital mortality,OR 1.368,95% CI 1.047-1.787,P = 0.022.Conclusion In patients with acute myocardial infarction,the presence of PCI increases the risk of worse in-hospital outcome.

Objective To observe the abnormal Minnesota code (MC) distribution and interrelated characteristic on electrocardiograms (ECGs) of the adult Kazakh population.Methods Resting ECGs and blood press of randomly sampled 30 000 adult Kazakh people in three Northern regions of Xinjiang were continuously examined and analyzed,using Minnesota code recommended by WHO as the classification of ECG.Results The overall rate of abnormal ECG findings was 248.60‰,and the main abnormality in males was 146.83‰,compared to 157.71‰ in females.The prevalence rates of abnormal ST-T changes,the total arrhythmia and atrial fibrillation (AF) were 100.03‰,71.17‰ and 2.83‰ respectively.There were statistically significant differences among the main abnormities from the three regions.Conclusion The ECGs abnormalities of adult Kazakh people were high.There was significant relation found between the main abnormalities and hypertension.The prevalence of AF was different from the domestically reported literature that calls for further study.

At present, cancer is still one of the most serious threats to human health. Despite the wide application of multiple cancer therapies in clinical practice, the therapeutic effects of most cancers are still far from satisfactory. In recent years, the discovery of regulated cell death may be a good first step on the road to treat cancer. Ferroptosis is triggered by lipid peroxidation of unsaturated fatty acids in cell membrane catalyzed by iron ion. It has been widely concerned as an emerging target for cancer therapy. With the booming of biomedical nanotechnology, ferroptosis as an emerging therapeutic target has attracted extensive attention. Here, we review the advance on the intersection of ferroptosis and biomedical nanotechnology. First, the research background of ferroptosis and nano-preparation as well as the feasibility of ferroptosis-based nano-drug delivery systems (nano-DDS) for cancer treatment are presented and analyzed. Then, the strategies for inducing ferroptosis based on nano-DDS are summarized, mainly including: the promotion of Fenton reaction, the inhibition of glutathione peroxidase 4 (GPX-4) and the restriction of the cysteine-glutamate exchange transporter (system Xc^-). Furthermore, the combination therapy strategies based on biomedical nanotechnology induced ferroptosis are also discussed. Finally, we shine the spotlight on the prospects and challenges of ferroptosis-based nanotherapeutics in clinical application.

Three cyclotides were isolated from the whole plant of Viola yedoensis in this study. The two, vary peptide E and cycloviolacin Y5, were previously reported, and a novel cycloviolacin VY1 was characterized according to the interpretation of MS/MS fragmentation of peptides which were produced from the reduced and alkylated parent peptide with the digestion of Endo Lys-C, trypsin and chymotrypsin, separately. The stability of remarkable resistance to proteolytic degradation by trypsin and chymotrypsin, and that of thermal denaturation was confirmed again. Besides, the IC50 value of cycloviolacin VY1 against influenza A H1N1 virus was (2.27 +/- 0.20) microg x mL(-1). It is the first cyclotide reported with anti-influenza A H1N1 virus activity in vitro assay.
Antiviral Agents ; isolation & purification ; pharmacology ; Cyclotides ; pharmacology ; Influenza A Virus, H1N1 Subtype ; drug effects ; Tandem Mass Spectrometry ; Viola ; chemistry

OBJECTIVETo evaluate the clinical efficacy of bladder gasification and stasis dispersion combined with antibiotic therapy in the treatment of III A chronic prostatitis.

METHODSWe conducted a randomized controlled clinical study on 120 III A prostatitis patients that all met the diagnostic criteria. We divided the patients into groups A, B and C of equal number to receive oral medication of sparfloxacin, sparfloxacin + tamsulosin, and sparfloxacin + herbal decoction, respectively, all for a course of 4 weeks. We evaluated the primary therapeutic indexes according to the total scores of the patients on traditional Chinese medicine (TCM) syndrome and NIH-CPSI and the secondary therapeutic indexes based on the count of white blood cells (WBC) in the expressed prostatic secretion (EPS).

RESULTSAfter treatment, the total scores on TCM syndrome and NIH-CPSI were significantly reduced in groups B (42.15 +/- 10.29 and 13.25 +/- 6.04) and C (41.26 +/- 11.25 and 12.38 +/- 7.19) than in A (49.43 +/- 11.09 and 17.62 +/- 5.84) ( P < 0.05), and so was the WBC count in EPS in group C (7.76 +/- 15.73) than in groups A (11.45 +/- 10.33) and B (12.28 +/- 13.81) (P < 0.05). The difference between pre- and post-treatment scores on TCM syndrome was more significant in group C (12.65 +/- 11.76) than in B (8.55 +/- 10.15) (P < 0.05).

CONCLUSIONBladder gasification and stasis dispersion combined with antibiotic therapy is effective for the treatment of III A chronic prostatitis, and therefore deserves wide clinical application.

Adult ; Anti-Bacterial Agents ; therapeutic use ; Chronic Disease ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Medicine, Chinese Traditional ; Phytotherapy ; Prostatitis ; classification ; drug therapy ; Treatment Outcome

Objective: To study retrovirus (RV)-mediated transduction of gastric carcinoma cells with the herpes simplex virus thymidine kinase (HSV-tk) gene and the subsequent treatment with ganciclovir(GCV). Methods: The TK gene was transfected into human gastric carcinoma cell line MKN28 using HSV-TK that packed with PA317 cell, the sensitivity of MKN28TK cells to GCV was examined in vitro. Results: The retroviral-mediated HSV-TK gene can be transfected to MKN28 cells. The growth rate of MKN28 cells transfected with HSV-TK gene did not change. MKN28TK cells became significantly sensitive to GCV and had bystander effect. Conclusion: Transfection of gastric carcinoma with HSV-TK has higher transfection efficiency. MKN28TK cells are significantly sensitive to GCV.

Objective: To study retrovirus (RV)-mediated transduction of gastric carcinoma cells with the herpes simplex virus thymidine kinase (HSV-tk) gene and the subsequent treatment with ganciclovir(GCV). Methods: The TK gene was transfected into human gastric carcinoma cell line MKN28 using HSV-TK that packed with PA317 cell, the sensitivity of MKN28TK cells to GCV was examined in vitro. Results: The retroviral-mediated HSV-TK gene can be transfected to MKN28 cells. The growth rate of MKN28 cells transfected with HSV-TK gene did not change. MKN28TK cells became significantly sensitive to GCV and had bystander effect. Conclusion: Transfection of gastric carcinoma with HSV-TK has higher transfection efficiency. MKN28TK cells are significantly sensitive to GCV.

Objective To evaluate the effect of intravenous thrombolysis with urokinasc for treatment of acute cerebral infarction due to vertebrobasilar artery ischemia.Methods Thirteen pafients with a clinical diagnosis of acute cerebral infarction arising from vertebrobasilar artery ischemia received thmmbolytic therapy with urokinase(5×105-1.5×106U) infused intravenously within 1 h.The NIH Stroke Scale(NIHSS)was used to evaluate the patients'neurological function before and at 0,6,24 hand at 7 and 14 days after the treatment.Modified Rankin Scale(MRS)was used for neurologiical assessment 3 months after the treatments. Results The mean NIHSS score of the patients was 17.46±6.19 before treatment and rapidly decreased to 7.92±6.43 24 h after the thrombolytic therapy.Three months after the therapy,8 patients had favorable clinical outcomes defined as capability of independent living(MRS score of 0-2);2 patients had a poor outcomes with assisted living,and 3 patients died.Bleeding occurred in 4 cases including 2 cerebral hemorrhage cases. Conclusion Favorable clinical outcome can be achieved with intravenous urokinase therapy in the majority of patients with acute cerebral infarction due to vertebrobasilar ischcrnia.