Valproate reduces retinal ganglion cell apoptosis in rats after optic nerve crush

The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.

ARID1A Inactivation Increases Expression of circ0008399 and Promotes Cisplatin Resistance in Bladder Cancer

Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladder cancer patients.AT-rich interaction domain 1A(ARID1A)gene mutation occurs frequently in bladder cancer;however,the role of CDDP sensitivity in BC has not been studied.Methods We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology.IC50 determination,flow cytometry analysis of apoptosis,and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A.qRT-PCR,Western blotting,RNA interference,bioinformatic analysis,and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC.Results It was found that ARID1A inactivation was associated with CDDP resistance in BC cells.Mechanically,loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3(EIF4A3)through epigenetic regulation.Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399(circ0008399),a novel circular RNA(circRNA)identified in our previous study,which,to some extent,showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells.Importantly,EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP.Conclusion Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.

High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer

BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.

The Prognostic Value of Pathological and Molecular Margins Marked by p53 and eIF4E in Laryngeal Carcinoma

Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was studied in 253 cases and 67 cases respectively, the latter were pathological negative margin chosen from the former. Immunohistochemisty was used to detect the expression of eIF4E and p53 proteins. Results: The rate of pathological, p53 and eIF4E positive margins was 20.2%, 19.4% and 32.8% respectively. The recurrent rate of those with positive margins was higher than that of negative margins, which including pathological margin (70.6% vs 35.1%, P =0.0000), p53 margin (69.2% vs 33.3%, P =0.018) and eIF4E margin (63.6% vs 28.9%, P =0.018); The survival rate of those with negative margins was higher than those with positive margins, including pathological margin (the 5-year cumulative survival rate was 37.52% and 64.37% respectively, P =0.0023), p53 margin (the 5-year cumulative survival rate was 24.62% and 75.69% respectively, P =0.0012) and eIF4E margin (the 5-year cumulative survival rate was 43.31% and 77.52% respectively, P =0.0006). Conclusion: The prognosis of those with both pathological and molecular positive margins was worse than that of the negative margins; Both the eIF4E and p53 were useful markers to pick out the poor prognostic patients from those with pathological negative margin, and the former seemed to be more potential.

Malignant Transformation and Abnormal Expression of Eukaryotic Initiation Factor in Bronchial Epithelial Cells Induced by Cadmium Chloride

Objective To analyze the relationship between malignant transformation and abnormal expression of eukaryotic initiation factor 3 （eIF3 p36） in human bronchial epithelial （16HBE） cells induced by cadmium chloride （CdCl2）. Methods 16HBE cells were treated several times with different concentrations of CdCl2. Tumorigenic potential of transformed cells was identified by assays for anchorage-independent growth in soft agar and for tumorigenicity in nude mice after the 35th passage. Total RNA was isolated from 16HBE cells induced by CdC12, including non-transformed, Cd-transformed, and Cd-tumorigenic cell lines. Special primers for eIF3 p36 were designed and the expression of eIF3 mRNA in different cell lines was detected with fluorescent quantitative-polymerase chain reaction technique （FQ-PCR）. Results The 35th passage of 16HBE cells transformed by CdCl2 exhibited overlapping growth. Compared with the non-transformed cells, colonies of transformed cell lines in soft agar showed statistically significant increases and dose-dependent effects （P〈0.01）. All Cd-induced transformed cell lines formed rumors in nude mice within 2 weeks of inoculation, but none of the mice injected with non-transformed cells showed tumors even after 3 weeks. All tumors were pathologically identified as poorly differentiated squamous cell carcinoma. The eIF3 p36 genes in different stages of 16HBE cells transformed by CdCl2 were elevated as compared with the non-transformed control （P〈0.01）, and the eIF3 expression increased with the degree of cell malignancy. Conclusion CdCl2 is capable of inducing morphological transformation in 16HBE cells and transformed cells are potentially tumorigenic. Over-expression of eIF3 p36 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2 and may be one of the molecular mechanisms potentially responsible for carcinogenesis due to Cd.

Detection of eukaryotic translation initiation factor 4E and its clinical significance in hepatocellular carcinoma

AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotting was performed to quantify the elF4E protein expression in the normal human liver cell line L02 and the hepatoma cell lines Hep3B, HepG2,and Huh7.Forty-six hepatocellular carcinoma samples with complete clinical data were obtained from Changzheng Hospital during the period of December 2008 to July 2009.The expression of eIF4E in the tumor samples and their adjacent tissues were detected by immunohistochemistry.The relationship between the test results and hepatocellular carcinoma(HCC) prognosis was statistically analysed by using a COX proportional hazard model. RESULTS:Western blotting analysis showed that there were distinct eIF4E protein bands in all three of the hepatoma cell lines.In particular,the HepG2 cell line had the highest level of eIF4E protein expression.The L02 cell group had a low eIF4E expression.Immunohistochemical assay showed that there were 32 cases in which the tumour tissue expression was higher than their adjacent tissues,accounting for 69.57%.There were also 14 cases in which the tumour tissue expression was lower or no significant difference was found, accounting for 30.43%.COX proportional hazards model analysis showed that HCC prognosis was related to the depth of invasion,the overexpression of eIF4E and p53, possibly as independent HCC prognostic predictors. CONCLUSION:In summary,eIF4E expression is associated with liver cancer,and patients with high eIF4E expression levels have a higher risk of recurrence.

Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress

Cerebral ischemia triggers secondary ischemia/reperfusion injury and endoplasmic reticulum stress initiates cell apoptosis. However, the regulatory mechanism of the signaling pathway remains unclear. We hypothesize that the regulatory mechanisms are mediated by the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α in the endoplasmic reticulum stress signaling pathway. To verify this hypothesis, we occluded the middle cerebral artery in rats to establish focal cerebral ischemia/reperfusion model. Results showed that the expression levels of protein kinase-like endoplasmic reticulum kinase and caspase-3, as well as the phosphorylation of eukaryotic initiation factor 2α, were increased after ischemia/reperfusion. Administration of atorvastatin decreased the expression of protein kinase-like endoplasmic reticulum kinase, caspase-3 and phosphorylated eukaryotic initiation factor 2α, reduced the infarct volume and improved ultrastructure in the rat brain. After salubrinal, the specific inhibitor of phosphorylated eukaryotic initiation factor 2α was given into the rats intragastrically, the expression levels of caspase-3 and phosphorylated eukaryotic initiation factor 2α in the were decreased, a reduction of the infarct volume and less ultrastructural damage were observed than the untreated, ischemic brain. However, salubrinal had no impact on the expression of protein kinase-like endoplasmic reticulum kinase. Experimental findings indicate that atorvastatin inhibits endoplasmic reticulum stress and exerts neuroprotective effects. The underlying mechanisms of attenuating ischemia/reperfusion injury are associated with the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/caspase-3 pathway.

Improved PSO algorithm based on chaos theory and its application to design flood hydrograph

The deficiencies of basic particle swarm optimization （bPSO） are its ubiquitous prematurity and its inability to seek the global optimal solution when optimizing complex high-dimensional functions. To overcome such deficiencies, the chaos-PSO （COSPSO） algorithm was established by introducing the chaos optimization mechanism and a global particle stagnation-disturbance strategy into bPSO. In the improved algorithm, chaotic movement was adopted for the particles＇ initial movement trajectories to replace the former stochastic movement, and the chaos factor was used to guide the particles＇ path. When the global particles were stagnant, the disturbance strategy was used to keep the particles in motion. Five benchmark optimizations were introduced to test COSPSO, and they proved that COSPSO can remarkably improve efficiency in optimizing complex functions. Finally, a case study of COSPSO in calculating design flood hydrographs demonstrated the applicability of the improved algorithm.

Crack propagation mechanism of compression-shear rock under static-dynamic loading and seepage water pressure

To reveal the water inrush mechanics of underground deep rock mass subjected to dynamic disturbance such as blasting, compression-shear rock crack initiation rule and the evolution of crack tip stress intensity factor are analyzed under static-dynamic loading and seepage water pressure on the basis of theoretical deduction and experimental research. It is shown that the major influence factors of the crack tip stress intensity factor are seepage pressure, dynamic load, static stress and crack angle. The existence of seepage water pressure aggravates propagation of branch cracks. With the seepage pressure increasing, the branch crack experiences unstable extension from stable propagation. The dynamic load in the direction of maximum main stress increases type I crack tip stress intensity factor and its influence on type II crack intensity factor is related with crack angle and material property. Crack initiation angle changes with the dynamic load. The initial crack initiation angle of type I dynamic crack fracture is 70.5°. The compression-shear crack initial strength is related to seepage pressure, confining pressure, and dynamic load. Experimental results verify that the initial crack strength increases with the confining pressure increasing, and decreases with the seepage pressure increasing.

Relationship between Eukaryotic Translation Initiation Factor 4E and Malignant Angiogenesis in Non-Hodgkin Lymphoma

The relationship between angiogenesis and eukaryotic translation initiation factor 4E （EIF4E） expression level in non Hodgkin lymphoma （NHL） was studied. Mean microvessel density （MVD） and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3.1 （＋） and transfected into Raji cells. A series of angiogenesis related factors,including vascular endothelial growth factor （VEGF）, matrix metalloproteinases 9 （MMP-9） and tissue inhibitor of metalloproteinases-2 （TIMP-2） proteins were detected by Western blot. The results showed that： （1） The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas（P〈0.05）and the expression of EIF4E was positively correlated with MVD in lymph node of NHL（r=0. 695, P〈0.01）. （2） Antisense EIF4E eukaryocytic expression vector （pcDNA3. 1-EIF4Eas） was constructed successfully. （3） EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells （NHPMC）, and blockage of EIF4E expression brought down the expression of VEGF and MMP-9. However, TIMP-2 was undetectable in Rail cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL.

Roles of HDAC2, eIF5, and eIF6 in Lung Cancer Tumorigenesis

Objective The expression levels of histone deacetylase 2(HDAC2),eukaryotic initiation factor 5(eIF5),and eukaryotic initiation factor 6(eIF6),and relationship between HDAC2 and eIF5 or eIF6 in lung cancer tissues were investigated,in order to charify the relationship between HDAC2 and the prognosis of lung cancer patients and its influence on the expression of eIF5 and eIF6.Methods The expression of HDAC2,eIF5,and eIF6 in lung cancer tissues was detected by quantitative reverse transcription polymerase chain reaction.The expression correlation between HDAC2 and eIF5 or eIF6 was tested using a t test.The correlation between HDAC2 and eIF5 or eIF6 was analyzed using the TCGA database.The identified cells were constructed with small interfering siRNA and HDAC2 overexpression plasmid.The proliferation and migration ability of the identified cells was investigated by CCK8 and Transwell assays,respectively.Results HDAC2,eIF5,and eIF6 were overexpressed in lung cancer tissues,and HDAC2 expression level was negatively correlated with the prognosis of lung cancer patients.HDAC2 expression level was positively correlated with eIF5 and eIF6 expression levels.HDAC2 could regulate the expression of eIF5 and eIF6.The regulation of proliferation and invasion of lung cancer cells by HDAC2 depended on eIF5 and eIF6.Conclusion HDAC2,eIF5,and eIF6 were closely related with lung cancer tumorigenesis,which might be potential biological markers and therapeutic targets for lung cancer.

Effect of Artemisia decoction on liver function and pERK/eIF2a signaling pathway in rats with alcoholic liver fibrosis

Objective: To investigate the effects of Artemisia decoction on liver function and phosphorylation of extracellular regulated protein kinase/eukaryotic translation initiation factor 2α (pERK/eIF2a) signaling pathway in rats with alcoholic liver fibrosis. Methods: A total of 40 healthy Sprague-Dole (SD) rats were randomly divided into 4 groups: the normal group, the sham operation group, the model group and the Artemisia decoction group, with 10 rats in each group. Alcoholic liver fibrosis model was established by "alcohol-corn oil-pyrazole" combined with a 12-week high-fat diet. After successful modeling, the normal group was not treated, and the sham operation group was given saline. The model group and the Artemisia decoction group were given the same amount of wormwood soup at the same time. The serum hydroxyproline (HYP), hyaluronidase (HA), laminin (LN), type IV collagen (CIV), type III procollagen (PIIINP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-TG), total bile acid (TBA), total bilirubin (TB), albumin (ALB), total cholesterol (CHOL), triglyceride (TG), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured after 12 weeks of continuous treatment. The degree of liver fibrosis was observed by hematoxylin-eosin staining (HE). The expression of pERK/eIF2a signaling pathway in liver tissue was detected by enzyme-linked immunosorbent assay (ELISA). Results: Compared with the normal group, the levels of serum HYP, HA, LN, CIV, PIIINP, AST, ALT, γ-GT, ALP, TBL and TB in the sham operation group were not significantly changed (P>0.05), while these indexes in the model group were significantly elevated (P<0.01). After treatment with Artemisia decoction, the levels of serum HYP, HA, LN, CIV, PIIINP, AST, ALT, γ-GT, ALP, TBL and TB were significantly lower than those in the model group (P<0.01). The serum albumin, lipid metabolism and oxidative damage indicators showed that there was no significant change in serum ALB, CHOL, TG, GSH, SOD and MDA levels in the sham operation group compared with the normal group (P>0.01). The levels of GSH and SOD in the model group were significantly decreased (P<0.01), and the levels of CHOL, TG and MDA in the model group were significantly increased (P<0.01). Compared with the model group, the serum ALB, GSH and SOD levels were significantly increased (P<0.01), and CHOL, TG and MDA levels were significantly decreased after giving intervention with Artemisia decoction (P<0.01). The results of HE staining showed that compared with the control group, the morphology of the liver sections of the sham operation group was normal, while the liver sections of the model group showed obvious vacuolization changes. The liver sections of the rats treated with Artemisia decoction were significantly improved. The results of ELISA showed that there was no significant change in the levels of pERK and eIF2a in the liver tissue of the sham operation group compared with the normal group (P>0.05). The levels of pERK and eIF2a in the liver tissue of the model group were significantly increased (P<0.01). After treatment with Artemisia decoction, the levels of pERK and eIF2a in rat liver tissues were significantly lower than those in the model group (P<0.01). Conclusion: Artemisia decoction can effectively block the degree of liver fibrosis in rats with alcoholic liver fibrosis, reduce liver fibrosis index and improve hepatobiliary function. This effect may be related to inhibition of the pERK/eIF2a signaling pathway.

Cloning and Expression Analysis of eIF5A Gene from Litopenaeus vannamei

Eukaryotic translation initiation factor 5A （eIFSA） is a protein-translation initiation factor in eukaryotic cells. Recent studies found that elFSA plays an important role in regulating the processes of cellular senescence and death, environmental stress response and immune response in animal and plant cells. In the present study, a cDNA containing the complete amino acid sequence of eIFSA was obtained for the first time by sequencing the Litopenaeus vannamei cDNA library, which contained a 474 bp long open reading frame encoding 157 amino acids, with the predicted molecular weight of about 17. 257 ku and theoretical isoelectric point of 5.06. Comparison analysis showed that the amino acid sequence of elFSA gene in L vannamei shared relatively high homology with that in other species. Real-time quantitative RT-PCR results indicated that the mRNA expression of elFSA gene in different tissues of L. vannamei exhibited no significant difference. Real-time quantitative RT-PCR analysis of L. vannamei hepatopancreas infected with WSSV, TSV and IHHNV showed that the mRNA levels of elFSA gene was re- spectively significantly increased, which was 2.2, 2.5 and 1.6 times of that in control group, indicating that eIFSA may be involved in the antiviral immune response of L. vannamei.

Cloning and Characterization of Eukaryotic Translation Initiation Factor 4E (eIF4E) Gene Family in Ipomoea batatas L. (Lam) for Understanding Hexaploid Sweetpotato-Virus Interactions

Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryotic translation initiation factor (eIF)4E, its isoforms, eIF(iso)4E, and the cap-binding protein (CBP) in plants, have been implicated in viral infections aside from their importance in protein synthesis. Full-length cDNA encoding these putative eIF targets from susceptible/resistant and unknown hexaploid sweetpotato (Ipomoea batatas L. Lam) were amplified based on primers designed from the diploid wild-type relative Ipomoea trifida consensus sequences, and designated IbeIF4E, IbeIF(iso)4E and IbCBP. Comparative analyses following direct-sequencing of PCR-amplified cDNAs versus the cloned cDNA sequences identified multiple homeoalleles: one to four IbeIF4E, two to three IbeIF(iso)4E, and two IbCBP within all cultivars tested. Open reading frames were in the length of 696 bp IbeIF4E, 606 bp IbeIF(iso)4E, and 675 bp IbCBP. The encoded single polypeptide lengths were 232, 202, and 225 amino acids for IbeIF4E, IbeIF(iso)4E, and IbCBP, with a calculated protein molecular mass of 26 kDa, 22.8 kDa, and 25.8 kDa, while their theoretical isoelectric points were 5.1, 5.57, and 6.6, respectively. Although the homeoalleles had similar sequence lengths, single nucleotide polymorphisms and multi-allelic variations were detected within the coding sequences. The multi-sequence alignment performed revealed a 66.9% - 96.7% sequence similarity between the predicted amino acid sequences obtained from the homeoalleles and closely related species. Furthermore, phylogenetic analysis revealed ancestral relationships between the eIF4E homeoalleles and other species. The outcome herein on the eIF4E superfamily and its correlation in sequence variations suggest opportunities to decipher the role of eIF4E in hexaploid sweetpotato feathery mottle virus infection.

Who Benefits More from Online Learning?An Empirical Study on Postgraduates’Online Knowledge-Sharing Behavior

Online knowledge-sharing is the key link to individuals in the digital era.Postgraduates are the core members of the future knowledge-based society.Exploring factors affecting postgraduates’online knowledge-sharing behavior is of significance promoting their fair enjoyment of digital dividends and contributing to the construction of Digital China.However,little literature exists on this topic.This study examines factors resulting in postgraduates’differentiated online knowledge-sharing behavior from two dimensions:social structure and individual initiative.The results of the questionnaire survey of 501 postgraduates show that:First,not all postgraduates are aborigines of the digital age;and structural factors(gender,school type,location,father’s occupation,and father’s education)have a significant impact on postgraduates’online knowledge-sharing behavior.These factors also have a greater impact on the quality of online knowledge-sharing than in a quantity sense.Second,the individual initiative factor(information literacy)also has a significant impact on postgraduates’online knowledge-sharing behavior.It has a greater impact on the quantity of online knowledge-sharing than in a quality sense.Third,there is a Matthew effect under the internet context,and certain effects of structural factors on online knowledge-sharing behavior are indirectly generated through individual initiative factors.Participants with privileged structural status show a higher level of information literacy,which further encourages them to be more active in online knowledge-sharing behavior and facilitates their high-quality production.

Process of Hypertrophic Scar Formation： Expression of Eukaryotic Initiation Factor 6

Background： Hypertrophic scar is one of the most common complications and often causes the disfigurement or deformity in bum or trauma patients. Therapeutic methods on hypertrophic scar treatment have limitations due to the poor understanding of mechanisms of hypertrophic scar formation. To throw light on the molecular mechanism of hypertrophic scar formation will definitely improve the outcome of the treatment. This study aimed to illustrate the negative role of eukaryotic initiation factor 6 （elF6） in the process of human hypertrophic scar tbrmation, and provide a possible indicator of hypertrophic scar treatment and a potential target molecule for hypertrophic scar. Methods： In the present study, we investigated the protein expression of elF6 in the human hypertrophic scar of different periods by immunohistochemistry and Western blot analysis. Results： In the hypertrophic scar tissue, elF6 expression was significantly decreased and absent in the basal layer of epidermis in the early period, and increased slowly and began to appear in the basal layer of epidermis by the scar formation time. Conclusions： This study confirmed that elF6 expression was significantly related to the development of hypertrophic scar, and the elF6 may be a target molecule for hypertrophic scar control or could be an indicator of the outcomes for other treatment modalities.

Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells

Background:Epithelial-mesenchymal transition(EMT) is believed to be the critical process in malignant tumor invasion and metastases,and has a great influence on improving the survival rate in non-small-cell lung cancer(NSCLC) patients.Recent studies suggested that eukaryotic initiation factor 5A-2(eIF5A-2) might serve as an adverse prognostic marker of survival.We detected eIF5A-2 in NSCLC A549 cells,and found that the invasive capability correlates with the eIF5A-2 expression.Methods:Transforming growth factor(TGF)-β1 was used to induce EMT in A549 cells.Western blotting,immunofluorescence,wound healing assay,and transwell-matrigel invasion chambers were used to identify phenotype changes.Western blotting was also used to observe changes of the expression of eIF5A-2.We down-regulated the eIF5A-2 expression using an eIF5A-2 siRNA and identified the phenotype changes by western blotting and immunofluorescence.We tested the change of migration and invasion capabilities of A549 cells by the wound healing assay and transwell-matrigel invasion chambers.Results:After stimulating with TGF-β1,almost all A549 cells changed to the mesenchymal phenotype and acquired more migration and invasion capabilities.These cells also had higher eIF5A-2 protein expression.Down-regulation of eIF5A-2 expression with eIF5A-2 siRNA transfection could change the cells from mesenchymal to epithelial phenotype and decrease tumor cell migration and invasive capabilities significantly.Conclusions:The expression of eIF5A-2 was up-regulated following EMT phenotype changes in A549 cells,which correlated with enhanced tumor invasion and metastatic capabilities.Furthermore,in the A549 cell line,the process of EMT phenotype change could be reversed by eIF5A-2 siRNA,with a consequent weakening of both invasive and metastatic capabilities.

Regulation of Eukaryotic Initiation Factor 4E and Its Isoform： Implications for Antiviral Strategy in Plants

In recent years, biotechnology has permitted regulation of the expression of endogenous plant genes to improve agronomlcally important traits. Genetic modification of crops has benefited from emerging knowledge of new genes, especially genes that exhibit novel functions, one of which is eukaryotlc initiation factor 4E （eIF4E）. eIF4E Is one of the most important translation initiation factors Involved in eukaryotic initiation. Recent research has demonstrated that virus resistance mediated by eIF4E and Its isoform elf （Iso）4E occurs in several plant-virus interactions, thus indicating a potential new role for eIF4E/elF（Iso）4E In resistance strategies against plant viruses. In this review, we briefly describe eIF4E activity In plant translation, its potential role, and functions of the eIF4E subfamily In plant-virus interactions. Other initiation factors such as elF4G could also play a role In plant resistance against viruses. Finally, the potential for developing eIF4E-mediated resistance to plant viruses in the future Is discussed. Future research should focus on elucidation of the resistance mechanism and spectrum mediated by eIF4E. Knowledge of a particu- lar plant-virus interaction will help to deepen our understanding of eIF4E and other eukaryotic Initiation factors, and their involvement in virus disease control.

The engine initiating tissue regeneration:does a common mechanism exist during evolution?

A successful tissue regeneration is a very complex process that requires a precise coordination of many molecular,cellular and physiological events.One of the critical steps is to convert the injury signals into regeneration signals to initiate tissue regeneration.Although many efforts have been made to investigate the mechanisms triggering tissue regeneration,the fundamental questions remain unresolved.One of the major obstacles is that the injury and the initiation of regeneration are two highly coupled processes and hard to separate from one another.In this article,we review the major events occurring at the early injury/regeneration stage in a range of species,and discuss the possible common mechanisms during initiation of tissue regeneration.

Tumor necrosis factor a accelerates Hep-2 cells proliferation by suppressing TRPP2 expression

TRPP2, a Ca2＋-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor a （TNF-a） is a proinflammatory cytokine extensively involved in immune system regulation, cell proliferation and cell survival. However, the effects and mechanisms for the role of TNF-a in laryngeal cancer remain unclear. Here, we demonstrated using western blot analyses and intracellular Ca〉 concentration measurements that TNF-a treatment suppressed both TRPP2 expression and ATP-induced Ca2＋ release in a laryngeal cancer cell line （Hep-2）. Knockdown of TRPP2 by a specific siRNA significantly decreased ATP-induced Ca2＋ release and abolished the effect of TNF-a on the ATP-induced Ca2＋ release. TNF-a treatment also enhanced Hep-2 cell proliferation and growth, as determined using cell counting and flow cytometry cell cycle assays. Moreover, TNF-a treatment down-regulated phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK） and phosphorylated eukaryotic translation initiation factor （p-elF2c0 expression levels, without affecting PERK and elF2ct expression levels in Hep-2 cells. We concluded that suppressing TRPP2 expression and TRPP2-mediated Ca2＋ signaling may be one mechanism underlying TNF〈t-enhanced Hep-2 cell proliferation. These results offer new insights into the mechanisms of TNF-a-mediated laryngeal cancer cell proliferation, and provide evidences showing a potential role of TNF-a in the development of laryngeal cancer.