An oncolytic adenovirus delivering TSLC1 inhibits Wnt signaling pathway and tumor growth in SMMC-7721 xenograft mice model

Tumor suppressor in lung cancer-1(TSLC1)was first identified as a tumor suppressor for lung cancer,and frequently downregulated in various types of cancers incl...     

Beneficial Effects of Schisandrin B on the Cardiac Function in Mice Model of Myocardial Infarction

The fruit of Schisandra chinensis has been used in the traditional Chinese medicine for thousands of years. Accumulating evidence suggests that Schisandrin B (Sch B) has cardioprotection effect on myocardial ischemia in vitro. However, it is unclear whether Sch B has beneficial effects on continuous myocardial ischemia in vivo. The aim of the present study was to investigate whether Sch B could improve cardiac function and attenuate myocardial remodeling after myocardial infarction (MI) in mice. Mice model of MI was established by permanent ligation of the left anterior descending (LAD) coronary artery. Then the MI mice were randomly treated with Sch B or vehicle alone. After treatment for 3 weeks, Sch B could increase survival rate, improve heart function and decrease infarct size compared with vehicle. Moreover, Sch B could down-regulate some inflammatory cytokines, activate eNOS pathway, inhibit cell apoptosis, and enhance cell proliferation. Further in vitro study on H9c2 cells showed similar effects of Sch B on prevention of hypoxia-induced inflammation and cell apoptosis. Taken together, our results demonstrate that Sch B can reduce inflammation, inhibit apoptosis, and improve cardiac function after ischemic injury. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.     

The subtype-specific molecular function of SPDEF in breast cancer and insights into prognostic significance

Breast cancer (BC) is a molecular diverse disease which becomes the most common malignancy among women worldwide. There are four BC subtypes (Luminal A, Luminal B, HER2-enriched and Basal-like) robustly established following gene expression pattern-based characterization, behave significant differences in terms of their incidence, risk factors, prognosis and therapeutic sensitivity. Thus, there is an urgent need to provide mechanism research, treatment strategies and/or prognosis evaluation based on the patient stratification of BC subtypes. The prostate-derived ETS factor SPDEF was first identified as an activator of prostate specific antigen, and then, the involvements in many aspects of BC have been proposed. However, the subtype-specific molecular function of SPDEF in BC and insights into prognostic significance have not been clearly elucidated. This study demonstrated for the first time that SPDEF may play a diversity role in the expression levels, clinicopathologic importance, biological function and prognostic evaluation in BC via bioinformatics and experimental evidence, which mainly depends on different BC subtyping. In summary, our findings would help to better understand the possible mechanisms of various BC subtypes and to find possible candidate genes for prognostic and therapeutic usage.     

Ssp1 promotes actin depolymerization and is involved in stress response and new end take-off control in fission yeast

The ssp1 gene encodes a protein kinase involved in alteration of cell polarity in Schizosaccharomyces pombe. ssp1 deletion causes stress sensitivity, reminiscent of defects in the stress-activated MAP kinase, Spc1; however, the two protein kinases do not act through the same pathway. Ssp1 is localized mainly in the cytoplasm, but after a rise in external osmolarity it is rapidly recruited to the plasma membrane, preferentially to active growth zones and septa. Loss of Ssp1 function inhibits actin relocalization during osmotic stress, in cdc3 and cdc8 mutant backgrounds, and in the presence of latrunculin A, implicating Ssp1 in promotion of actin depolymerization. We propose a model in which Ssp1 can be activated independently of Spc1 and can partially compensate for its loss. The ssp1 deletion mutant exhibited monopolar actin distribution, but new end take-off (NETO) could be induced in these cells by exposure to KCl or to latrunculin A pulse treatment. This treatment induced NETO in cdc10 cells arrested in G1 but not in tea1 cells. This suggests that cells that contain intact cell end markers are competent to undergo NETO throughout interphase, and Ssp1 is involved in generating the NETO stimulus by enlarging the actin monomer pool.     

Ectopic expression of a cyanobacterial flavodoxin in creeping bentgrass impacts plant development and confers broad abiotic stress tolerance

Flavodoxin (Fld) plays a pivotal role in photosynthetic microorganisms as an alternative electron carrier flavoprotein under adverse environmental conditions. Cyanobacterial Fld has been demonstrated to be able to substitute ferredoxin of higher plants in most electron transfer processes under stressful conditions. We have explored the potential of Fld for use in improving plant stress response in creeping bentgrass (Agrostis stolonifera L.). Overexpression of Fld altered plant growth and development. Most significantly, transgenic plants exhibited drastically enhanced performance under oxidative, drought and heat stress as well as nitrogen (N) starvation, which was associated with higher water retention and cell membrane integrity than wild‐type controls, modified expression of heat‐shock protein genes, production of more reduced thioredoxin, elevated N accumulation and total chlorophyll content as well as up‐regulated expression of nitrite reductase and N transporter genes. Further analysis revealed that the expression of other stress‐related genes was also impacted in Fld‐expressing transgenics. Our data establish a key role of Fld in modulating plant growth and development and plant response to multiple sources of adverse environmental conditions in crop species. This demonstrates the feasibility of manipulating Fld in crop species for genetic engineering of plant stress tolerance.     

Synthesis of Drosophila melanogaster acetylcholinesterase gene using yeast preferred codons and its expression in Pichia pastoris

To improve the expression level of recombinant Drosophila melanogaster AChE (R-DmAChE) in Pichia pastoris, the cDNA of DmAChE was first optimized and synthesized based on the preferred codon usage of P. pastoris. The synthesized AChE cDNA without glycosylphosphatidylinositol (GPI) signal peptide sequence was then ligated to the P. pastoris expression vector, generating the plasmid pPIC9K/DmAChE. The linearized plasmid was homologously integrated into the genome of P. pastoris GS115 via electrotransformation. Finally seven transformants with high expression level of R-DmAChE activity were obtained. The highest production of R-DmAChE in shake-flask culture after 5-day induction by methanol was 718.50 units/mL, which was about three times higher than our previous expression level of native DmAChE gene in P. pastoris. Thus, these new strains with the ability to secret R-DmAChE in the medium could be used for production of R-DmAChE to decrease the cost of the enzyme expense for rapid detection of organophosphate and carbamate insecticide residues.