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BACKGROUND:Skin damage caused by radiation therapy and nuclear accidents is still a serious medical problem.It is difficult to achieve effective treatment results with single prevention and treatment methods.It is an important research direction to find new comprehensive treatment methods. OBJECTIVE:To observe the protective effect and the underlying mechanism of 1,2-propanediol combined with hepatocyte growth factor-modified exosomes derived from dental pulp stem cells on human epidermal radiation damage cell models. METHODS:(1)After infection of human dental pulp stem cells using recombinant adenovirus of human hepatocyte growth factor gene,exosomes,i.e.,Ad.HGF DPSC-Exo,were isolated with ultracentrifugation.(2)HaCat cells were irradiated with X-ray.The cells were treated with 1,2-propanediol before irradiation and Ad.HGF DPSC-Exo after irradiation.Cell proliferative activity was determined by CCK-8 assay.Cell apoptosis was detected by flow cytometry.Cell migration was detected by cell scratch assay.The expression levels of P21 and P53 were detected by PCR. RESULTS AND CONCLUSION:1,2-Propanediol,Ad.HGF.DPSC-Exo,Ad.HGF.DPSC-Exo + 1,2-propanediol could significantly improve the growth inhibition of HaCaT cells,reduce cell apoptosis,elevate cell proliferation and migration,and exhibit a good radiation protection effect.Moreover,the combined effect of Ad.HGF.DPSC-Exo + 1,2-propanediol was better.Furthermore,Ad.HGF.DPSC-Exo + 1,2-propanediol alleviated the cellular G2/M phase block and decreased the expression of cell cycle genes P53 and P21.In conclusion,1,2-propanediol pretreatment combined with Ad.HGF.DPSC-Exo had significant protective effects on radiation-induced HaCaT cell injury and it provided novel ideas and potential methods for the prevention and treatment of radiation-induced skin damage.

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Objective @#To investigate the effects of C-type lectin domain family 5，member A( CLEC5A) on the pro- liferation，apoptosis，and cell cycle of leukemia cell lines THP-1 and K562，and the underlying mechanism．@*Methods @#The expression of CLEC5A in leukemia patients was investigated in the GEPIA database. Recombined plasmid containing CLEC5A was transfected into THP-1 and K562 cells for overexpression of CLEC5A．Small interfering RNA(siRNA) was used to knock down the endogenous CLEC5A in leukemia cells．CCK-8 and EdU assays were used to assess the leukemia cells proliferation．Flow cytometry was used to assess cell cycle．Flow cytometry was used to assess cell apoptosis under hydrogen peroxide( H2 O2 ) stress．The RNA sequencing( RNA-seq) and pathway enrichment analysis were used to analyze the signal pathways of significant enrichment of up-regulated or down-reg- ulated genes after knocking down CLEC5A gene．Protein expression levels of several members in AKT1 / mTOR and p53 signaling pathways were detected by Western blot assays. @*Results @#CLEC5A was significantly up-regulated in bone marrow tissues of leukemia patients compared to the matched non-tumor tissues of healthy individuals．Knock- down of CLEC5A significantly reduced the proliferation(all P＜0. 01) and S phase progression(all P＜0. 05) ，and increased the apoptosis(all P＜0. 001) under H2 O2 stress，in THP-1 and K562 cells．Conversely，overexpression of CLEC5A significantly increased the proliferation(all P ＜0. 001) and S phase progression ( all P ＜0. 01) ，and re- duced the apoptosis(all P＜0. 01) under H2 O2 stress，in THP-1 and K562 cells．The uregulated genes were sig- nificantly enriched in AKT1-mTOR and other signal pathways after knocking down CLEC5A，while the down-regula- ted genes were significantly enriched in cell cycle signal pathways．CLEC5A in leukemia cells significantly reduced the genes expression levels of BAX and p53，and significantly induced the gene expression levels of BCL-2 and phosphorylation levels of AKT1 and mTOR proteins．@*Conclusion @#CLEC5A increases the cell cycle and proliferation and inhibits cells apoptosis in THP-1 and K562 cells，and the mechanism may be related to activating the AKT / mTOR and p53 signaling pathways.

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Objective @#To investigate how the m6 A methylation enzyme Methyltransferase like protein 16 ( METTL16) exerts its effects on the proliferation，migration and invasion of hepatocellular carcinoma (HCC) cells HepG2 and HCC-LM3，and to further explore the underlying molecular mechanism.@*Methods @#The overexpression and RNA interference vectors targeting METTL16 were transfected into HepG2 and HCC-LM3 cells and screened the stable cell lines by purimycin．The expressions of METTL16 were detected by means of qRT-PCR and Western blot assay ; in HCC cell lines，Cell counting kit-8 ( CCK-8) ，Transwell assays，and flow cytometry were used to ob- serve the effects in the proliferation，migration，invasion and cell cycle after transfection ; Western blot assay was used todetect the effect of expression of VEGFA-VEGFR2 pathway-related proteins in hepatocellular carcinoma cells ; Gene Expression Omnibus database was used to analyzethe expression levels of METTL16 in human liver cancer tissues and paraneoplastic tissues．Log-rank test was used to compare the clinic pathological characteristics between patients with high and low expression of METTL16 in hepatocellular carcinoma. @*Results @#Western blot and real-time quantitative PCR experiments showed that METTL16 overexpressing cell lines and interfering cell lines were successfully constructed in HepG2 and HCC-LM3 cells．CCK-8，Transwell and flow cytometry results showed that overexpression of METTL16 resulted in a decrease in the number of proliferating，migrating and invasive cells， and the number of cells in G2 / M phase proportion increased．Western blot showed that overexpression of METTL16 inhibited the expression of VEGFA-VEGFR2 pathway-related proteins VEGFR2，p-AKT，Cyclin B，and CDK1 in HepG2 cells，but knockdown of METTL16 reversed the inhibition effect on these proteins．Compared to the matched non-tumor liver tissues，METTL16 was downregulated in HCC tissues ; however，the levels of METTL16 were not significantly associated with the clinic pathological characteristics of HCC patients．@*Conclusion @#METTL16 may in- hibit the proliferation，migration and invasion of HCC cells by inhibiting the VEGFR2 pathway.

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Objective To investigate whether the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) can act as a competitive endogenous RNA (ceRNA) to promote the migration of hepatocellular carcinoma (HCC) cells.Methods Transient transfection of small interfering RNA (siRNA) against MALAT1 was used to knockdown MALAT1 in HepG2 cells.Transwell assays were employed to assess the migration capabilities of HepG2 cells upon MALAT1 knockdown.RNA pull-down assays were performed to validate the direct binding between MALAT1 and miR-126*.Quantitative reverse transcription PCR (qRT-PCR) and Western blotting assays were used to detect the mRNA and protein levels of the miR-126* target genes.The dysregulation and prognostic significance of MALAT1 and miR-126* were analyzed in the public dataset of The Cancer Genome Atlas (TCGA).Results Compared with the control group, MALAT1 knockdown significantly inhibited the migration of HCC cells.MALAT1, with three miR-126* response elements, directly sponged miR-126* in a sequence-specific manner.The mRNA and protein levels of CXCL12, which was the miR-126* target gene, were significantly down-regulated upon MALAT1 knockdown.The TCGA database showed that MALAT1 was significantly up-regulated in HCC and high expression levels of MALAT1 were significantly associated with poor disease-free survival, whereas an opposite pattern of miR-126* was observed.Conclusion This study suggests that MALAT1 directly sponges miR-126* and upregulates the expression of CXCL12, which in turn promotes the migration of HCC cells.

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During medical rescue for nuclear and radiation accidents, triage of potential victims could contribute to better use of medical resources currently and higher efficiency of the rescue.Biological dose estimation techniques ( estimated biodosimetry) are effective for assessing the degree of external radiation injury.The application of estimated biodosimetry to triage is important for effective nuclear accident medical rescue.In this paper, the characteristics of the estimated biodosimetry and its application to triage during medical rescue for nuclear accident and radiation were discussed.

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Hepatocellular carcinoma ( HCC) , as one of the most common malignant neoplasms , has a relatively high morbidity and mortality rate worldwide.MicroRNAs (miRNAs),a type of comparatively conserved endogenous small non-coding RNAs, function as pivotal regulators involved in various biological functions through the post -transcriptional regulation of gene expression .Some miRNA genes are arranged into a intandem model and reside close together on the same chromosome , forming miRNA clusters . These clustered miRNAs are mostly located on polycistronic transcripts and expressed at similar levels.In the human imprinted 14q32 region, 52 miRNA genes are organized as a large cluster which spans about 220 kb of the long arm ( q) .Lines of evidence show that dysregulation of miRNAs in this cluster are involved in the development of HCC .This review summarizes the structural characteristics of 14 q32 miRNA cluster as well as its impact on HCC in initiation and progression .

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Genomic polymorphisms come in various forms including single nucleotide variations, translocations, insertions and copy number variations (CNVs). As a form of structural variation, the CNVs comprise common and rare forms based on their populational frequencies. Studies have demonstrated that certain CNVs are associated with risks for neuro-developmental diseases, viral infections, chronic inflammations, and cancers. With the development of high-resolution genome typing technologies such as microarrays and whole genome sequencing, the human genomic CNVs map has been continuously improved and refined. In-depth study of CNVs not only can provide comprehensive understanding for their structural variations and genetic evolution, but also provide new insights into genetic factors contributing to such diseases. In this paper, the general characteristics, pathogenesis and detection methods for the CNVs, as well as their association with human diseases are reviewed.

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Objective To investigate the effect of AlkB homologue 5 ( ALKBH5 ) on proliferation, cell cycle, and apoptosis of HepG2 and L-02 cells.Methods Recombinant plasmid vector containing the CDS region of ALKBH5 (pEGFP-C1b-ALKBH5) was stably transfected into HepG2 and L-02 cells.Western blotting was used to detect the expression of green fluonescence protein ( GFP )-ALKBH5.There were two groups in our experiment: GFP-ALKBH5 lentivirus group and GFP lentivirus group.Characteristics, such as proliferation, cell cycle and apoptosis of HepG2 and L-02,were detected through Cell Counting Kit-8 (CCK-8) assay, flow cytometry and clone formation, respectively.Results The result of Western blotting revealed that ALKBH5 was efficiently up-regulated at protein levels.Despite apoptosis, phenotypic analysis revealed that the proliferation and cell phases were significantly inhibited in ALKBH5 overexpressed stable cell strains compared with the control cells (both P<0.05).Conclusion ALKBH5 can restrain fetal liver cell (L-02) and hepatocellular carcinoma cell (HepG2) from proliferating.Taken together, our results strongly suggest that ALKBH5 can play a key role in the generation and progression in HCC as a tumor suppressor.

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The integrator complex is multifunctional and contains at least 12 evolutionarily conserved subunits in hu-mans.It interacts with the C-terminal tail of the largest subunit of RNA-polymeraseⅡ ( RNAPⅡ) to promote 3′-end pro-cessing of small nuclear RNA (snRNA) U1/U2.It also interacts with RNAPⅡ, NELF and Spt5 to regulate NELF-mediated RNAPⅡpause/release and processivity at coding genes .Recently, the integrator complex is also reported to be involved in DNA damage response , dynein recruitment to the nuclear envelope , integrity of Cajal bodies , adipose differentiation , hem-atopoiesis , ciliogenesis , tumorigenesis and generation of viral microRNAs .This review discusses related research progress in the integrator complex .

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Alternative polyadenylation ( APA) is a widespread phenomenon and an important layer of gene regulation . APA contributes to the complexity of the transcriptome by allowing a single gene to encode multiple mRNA isoforms that dif -fer either in their coding sequence or in their 3′untranslated regions (3′UTR).The length of the 3′UTR can affect the sta-bility, localization and efficiency of the messenger RNAs ( mRNAs) by altering binding sites of RNA binding proteins or mi-croRNAs(miRNAs).The polyadenylation process , mechanisms governing APA and biological consequences resulting from APA are only starting to be deciphered .Here, we review the research progress in APA .

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Hereditary hemochromatosis (HHC) is a rare autosomal recessive disorder. We recruited a consanguineous Chinese family including the proband with HHC and other four members without HHC. Using whole-exome sequencing, we identified two homozygous mutations (c.G18C [p.Q6H] and c.GC962_963AA [p.C321X]) in the hemojuvelin gene (HJV) in the proband with HHC. No mutation was found in other four previously identified HHC related genes, HAMP, TFR2, FPN and HFE. The functional impact of p.Q6H mutation is weak whereas p.C321X, a premature termination mutation, results in a truncated HJV protein, which lacks the glycosylphosphatidylinositol (GPI) anchor domain. In addition to the mutations in HJV, other 12 homozygous mutations were identified in this patient. However, none of these mutations showed strong damaging impact and the mutated genes are not related to iron metabolism. Our in-house data further demonstrated that p.C321X is absent in the general Chinese population, suggesting that the homozygous mutation p.C321X in HJV is causative in the patient with HHC. Accordingly, all of the four members without HHC from the same family carried wild-type alleles or heterozygous mutations, but not the homozygous mutation in this site. Thus, we found for the first time that the homozygous mutation p.C321X in HJV can result in HHC, which will help genetic diagnosis and prenatal counseling for HHC.

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Objective To explore the association between tumor necrosis factor receptor associated factor 6 (TRAF6) polymorphisms and the susceptibility to sepsis. Method Haplotype tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database. The htSNPs were genotyped in 255 patients with sepsis and 260 control subjects by the Beckman SNP stream genotyping platform. The association with susceptibility to and severity of sepsis were estimated by logistic regression with adjustment for age, sex, smoking, drinking,chronic diseases status, APACHE Ⅱ score and critical illness. Results Of 13 TRAF6 ANPs, 7 were tagged by htSNPs. Of them, 5 htSNPs (rs5030496, rs5030411, rs5030416, rs5030445 and rs3740961) were used for final genotyping analysis. Genotype frequencies of those htSNPs were conformed to the Hardy-Weinberg law in both patients and controls. There were no significant association found between the 5 htSNPs and susceptibility to sepsis.Also, there was no significant association between the TRAF6 polymorphisms and the septic shock, death from sepsis as well as organ dysfunction. Conclusions The TRAF6 gene polymorphisms might not play a major role in severity of sepsis.

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Although significant advances have been made in both the development of therapeutic strate-gies and the understanding of pathophysiological mechanisms of sepsis, the mortality of severe sepsis and septic shock still remains unacceptably high worldwide. Current prediction models based on socio-demo-graphic and clinical risk factors fail to explain fully why a particular patient either develops or succumbs to sepsis. In recent years epidemiological studies have suggested a strong genetic relationship on the suscepti-bility and outcome of sepsis. With the completion of Human Genome Project and International HapMap Pro-ject, the identification of susceptibal genes contributing to sepsis may allow more precise use of interven-tions, such as targeted therapy of sepsis is an appealing strategy. In this review, we summarize a broad over-view of genetic nomenclature, study designs, and problems of these genetic association studies.

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More and more DNA sequences have been obtained since the start-up of human genome project. Powerful system is badly needed for data mining on these DNA sequences. Based on a personal computer and Linux operating system, the Phred/Phrap/Consed software and Blast software were used to construct a platform for batch analysis of the sequences, including identifying raw DNA sequence from chromatogram file, vector sequence removing, contig analysis (sequence assembly), repeat sequence identifying and sequence similarity analysis. Result demonstrated that this robust platform could accelerate data analysis for large-scale DNA sequencing.