Hyperplasia of smooth muscle cells is a major aspect of airway remodeling in asthma .In recent years.It is found that the epigenetic regulation plays an important role on the proliferation of airway smooth muscle cells and the secretion of inflammatory cytokines , including DNA methyltransferase inhibitors to inhibit the phenotype trans-formation;histone acetylation related with hypertrophy .In addition , the microRNA is potentially related with the regulation of a variety of physiological functions of airway smooth muscle cells of asthma model , including inhibition of proliferation and release of inflammatory factors .Hope that epigenetics can become a new target for the treatment of asthma .

In recent years, with the rapid development of antibody drugs, the antibody-based therapies have gradually expanded from the cancer and autoimmune diseases to metabolic and infectious diseases and so on. However, the development of antibody-based anti-infective drugs is much slower as there are only two kinds of drugs in the market. This is due to the complex infective mechanism of viruses, bacteria and other pathogens, and the monovalent character of monoclonal antibodies that greatly limit the anti-infection effect of antibody drugs. The development and application of novel technologies, such as recombinant polyclonal antibody technology, will greatly accelerate the development of antibody-based anti-infection drugs. This article will introduce the application and trends in the development of antibody-based drugs in the field of anti-infection therapy.
Anti-Infective Agents ; pharmacology ; Antibodies, Monoclonal ; pharmacology ; Drug Design ; Humans

Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Purpura, Thrombotic Thrombocytopenic ; etiology ; Transplantation, Autologous

Objective:To observe the clinical effects of acupuncture plus external medicine application for cervical radiculopathy.Methods:A total of 98 patients with cervical radiculopathy were randomly divided into an observation group and a control group based on the random digital table.The observation group (50 cases) was treated by acupuncture plus external medicine application and the control group (48 cases) was treated by acupuncture alone.The patients received the treatment every day.Ten sessions made a course.Cervical spondylosis symptom scale was used to assess the cases before and after the treatment.The clinical efficacy was compared between the two groups after the treatment.Results:The total effective rate was 98.1％ in the observation group versus 87.6％ in the control group with a statistically significant difference between the two groups (P＜0.05).The cure rate was 52.0％ in the observation group versus 18.8％ in the control group with a significant difference between the two groups (P＜0.05).There was no significant difference in the score of cervical spondylosis symptom scale between the two groups before the treatment (P＞0.05).It increased with a significant difference in both groups after the treatment (both P＜0.05),while a significant difference was found in the results between the two groups after the treatment (P＜0.05).Conclusion:Acupuncture plus external medicine application is more effective than acupuncture alone for treating cervical radiculopathy.The method also effectively improves the clinical symptoms.

A growing body of evidence has indicated the important role of autophagy receptors in directing ubiquitinated or non-ubiquitinated cargos towards autophagy. Autophagy receptors bind to LC3 (microtubule-associated protein 1 light chain 3) on phagophore and autophagosome membranes, and recognize signals on cargoes in the delivery system of autophagy. However, the diverse domains in the receptor structures determine that their roles would never be limited to autophagy. Up to date, increasing numbers of the receptor proteins have been demonstrated to serve as a molecular link or switch participating in autophagic degradation, apoptosis or cell survival signals. Here, we highlight the non-autophagic roles of these receptor proteins to draw attention to this growing research topic.
Apoptosis ; Autophagy ; Humans ; Microtubule-Associated Proteins ; physiology ; Signal Transduction ; Ubiquitination

Objective To isolate and cultivate mouse hepatic progenitor cells (mHPCs) from E14.5 mouse fetal liver in vitro and induce mHPCs differentiation into cholangiocytes.Methods Isolation of mHPCs from mouse fetal liver was based on the cell surface antigen delta-like protein 1/preadipocyte factor 1 (Dlk/Pref-1) by a fluorescence-activated cell sorter (FACS).Then mHPCs isolated were co-cultured with/without mouse embryonic fibroblasts (MEFs) by using Transwell.The cell antigen alpha-fetoprotein (AFP), albumin (ALB) and cytokeratin19 (CK19) expression in freshly isolated DLK1+cells or co-cultured for 4 days and 6 days were observed with immunocytochemical method.Results When co-cultured with MEFs, the division and proliferation were observed in most of DLK1+ cells and grape-like aggregation was formed.Cells began to adhere to growth and began to become spindle-shaped on 4th day.The DLK1+cells isolated freshly by FACS were expressed AFP and low levels of ALB but not expressed CK19.But, these cells expressed CK 19 and weak expression of ALB on 4th day.In addition, the expression of CK19 increased and the expression of ALB almost not detected on 6th day.Conclusions Most of DLK1+ cells, isolated from E14.5 fetal livers by FACS, are proved to be mHPCs.Furthermore, these cells can proliferate quickly and differentiate into cholangiocytes by co-culture with MEFs.

Objective To construct and identify the efficacy of a lentiviral vector harboring RNAi sequence targe-ting NSBP1 gene. Methods Three siRNA targeting the NSBP1 mRNA were designed, the pGCSIL-GFP-NSBP1 lentivirus vectors were constructed and confirmed by DNA sequencing. A total of 293T cells were co-transfected with pGCSIL-GFP-NSBP1, pHelper1.0 and pHelper2.0 for the virus stocks produced, the titer of the virus was test-ed. After lentivirus transfecting into DU145 ceils, Western-blot and MTT methods were used to determine the ex-pression and biological activity of NSBP1 gene, the cells were transplanted into nude mice, then inhibitive effect was observed. Results PCR analysis and DNA sequencing demonstrated that the RNAi sequence targeting the hu-man NSBP1 gene was successfully inserted into the lentiviral vector. The titer of the recombinant]entiviral vector was 2 × 10~8TU/mL. NSBP1 protein expression level in transfected cells was significantly decreased and growth rate of cells transfected with lentivirus was decreased by MTT assay, the downregulation of NSBP1 reduced growth rate of transplantated tumor, whereas tumorgenicity was not influenced. Conclusion The construction of the]entiviral vector of NSBP1 has been successfully prepared and NSBP1 plays an important regulatory role in androgen-inde-pendent prostate cancer cell proliferation.

Objective To investigate the character and location of a novel gene R049 and its expressed protein in uropathogenic Escherichia coli(UPEC) strain 132 isolated in China. MethodsThe chromosome library of UPEC132 was constructed by a shotgun strategy and the sequence analysis was carried out by a high-throughput pyrophosphate sequencing. Sequence reads were assembled with the Newbler program.The characters of R049-associated specific fragment were analyzed using the bioinformatics methods. Outer and inner membrane proteins of UPEC132 were extracted and then detected by SDS-PAGE and Western blot analysis together with the whole-cell lysates. ResultsThe 169 022 bp contig containing gene R049 was obtained and its sequence was very similar to the chromosome associated sequence of UPEC strain 536. It showed that a 20 773 bp fragment including R049 replaced the pathogenicity island PAI Ⅲ536 of UPEC536 in above 169 022 bp contig. The fragment had a lower GC content (46.97％) and 16 bp direct repeats in two ends. Significantly it also was adjacented to thrW tRNA, insertion element and genes coding integrase. Thus the 20 773 bp fragment was named R049 genome island(R049-GI). There were 25 ORFs in R049-GI, and gene R049 was located in the thirteenth ORF. The results of SDS-PAGE and Western blot revealed gene R049 encoded an outer membrane protein in the size of 47.0× 103. ConclusionGene R049, encoding an outer membrane protein, was a component part of the genome island in UPEC 132 chromosome acquired by horizontal gene transfer.

Objective To investigate the expression of soluble triggering receptors expressed on myeloid cells-1 ( sTREM-1 ) in intraperitoneal drainage fluid of patients with abdorminal trauma and its predictive value for post-traumatic sepsis. Methods A total of 80 abdominal trauma patients were served as the trauma group and 25 patients treated with subtotal gastrectomy as the control group.Intraperitoneal drainage fluid sTREM-1,serum sTREM-1,procalcitonin (PCT) and C-reactive protein (CRP)at 0,24,48,72 hours after admission were determined in two groups for assessing their value in early prediction of post-traumatic sepsis. Results The levels of drainage fluid sTREM-1,serum sTREM-1,PCT and CRP in the trauma group were significantly higher than those in the control group (P ＜ 0.05 ).Drainage fluid sTREM-1 showed the area under the receiver operating characteristic (ROC) curve,sensitivity and specificity for 0.84,77％,and 83％ in the prediction of post-traumatic sepsis,which was superior to the serum sTREM-1,PCT and CRP. Conclusion Intraperitoneal drainage fluid sTREM-1 has high accuracy in predicting the sepsis in abdominal trauma patients.

Objective To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) pathway in the protective effect of remifentanil or ischemic preconditioning (IPC) against hepatic ischemia-reperfusion (I/R) injury in rats.Methods One hundred and forty-four male SD rats,weighing 200-250 g,were randomly assigned into 6 group ( n =24 each):sham operation group (group S),I/R group,remifentanil group (group R),IPC group,SB203580 (a specific p38MAPK inhibitor) + remifentanil group (group SB + R),and SB + IPC group.The animals were anesthetized with intraperitoneal 20％ urethane 1 mg/kg.Partial liver ischemia was produced by clamping the hepatic pedicle supplying left lobe and middle lobe for 30 min,followed by 120 min reperfusion.In group R,remifentanil was infused intravenously at 2μg· kg- 1 · min- 1 starting from 30 min before ischemia until the end of reperfusion.In IPC group,the rats were subjected to 3 episodes of 5 min ischemia at 5 min intervals before I/R.SB203580 0.2 mg/kg was injected intravenously at 5 min before remifentanil infusion or IPC in groups SB + R and SB + IPC,and the equal volume of normal saline was given in the other groups.Six rats in each group were selected at 30,60,90 and 120 min of reperfusion and venous blood samples were taken from inferior vena cava for measurement of serum ALT and AST activities and concentrations of TNF-a and 1L-1β.The rats were then sacrificed and liver tissues were taken for microscopic examination and determination of phosphor-p38MAPK expression by Western blot.Results Compared with group S,serum AST and ALT activities and serum levels of TNF-α and IL-1β were significantly increased at each time point (P ＜ 0.05) and pathological injury was aggravated in group I/R.Compared with group I/R,serum AST and ALT activities and serum levels of TNF-a and IL-lβ were significantly decreased and phosphor-p38MAPK expression was up-regulated at 90 min of reperfusion in groups R and IPC ( P ＜ 0.05).The serum AST and ALT activities and serum levels of TNF-α and IL-1β were significantly increased,phosphor-p38MAPK expression was down-regulated at 90 min of reperfusion ( P ＜ 0.05),and pathological injury was aggravated in group SB + R compared with group R,and in group SB + IPC compared with group IPC.Conclusion Activation of p38MAPK pathway and inhibition of inflammatory response may be involved in the mechanism by which remifentanil or IPC reduces the hepatic I/R injury in rats.