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.

Objective: To investigate the function and potential mechanism of hepatocellular carcinoma(HCC) cells-derived extracellular nicotinamide phosphoribosyl transferase(eNAMPT) in the angiogenesis of human umbilical vein endothelial cells(HUVEC). Methods: The eNAMPT secretion of HCC cells were stimulated by hypoxia treatment and investigated the angiogenesis of HUVEC was investigated by tube formation assays. Transcriptomic RNA sequencing(RNA-seq) analyses of HUVEC under eNAMPT treatment were used to explore the mechanism of the effect of eNAMPT-insulin receptor(INSR) axis on angiogenesis. Western blot was used to detect the effects of eNAMPT-INSR axis on protein expression of HUVEC cells. qRT-PCR was used to detect the influence of eNAMPT-INSR axis on the expression of HUVEC intracellular related target genes. Results: ELISA and Western blot results showed that the protein level of eNAMPT in the culture supernatant of HCC cells increased significantly after hypoxia stimulation.In vitroangiogenesis assay results showed that eNAMPT significantly increased the nodules number and total length of tubes in HUVEC. The transcriptome sequencing results of HUVEC showed that eNAMPT, as an insulin analogue, participated in the regulation of biological processes such as cell migration and angiogenesis in HUVEC, and might promote angiogenesis by activating insulin-like signaling pathways. Western blot results showed that the eNAMPT-INSR axis affected p-AKT and p-ERK1/2 protein levels in PI3K-AKT and MAPK-ERK1/2 signaling pathways in HUVEC. qRT-PCR results showed that the eNAMPT-INSR axis affected the expression of angiogenesis related target genes MMP2, MMP9 and VEGF in HUVEC. Conclusion eNAMPT secreted by HCC cells promotes angiogenesis by binding INSR to activate the PI3K-AKT and MAPK-ERK1/2 signaling pathways.

Objective To investigate the effect of the mediator of DNA damage check point protein 1(MDC1)on proliferation,migration,invasion,cell cycle and cell apoptosis in cholangiocarcinoma(CCA)and the potential molecular mechanism.Methods The small interfering RNA(siRNA)specifically targeting MDC1 was used to transiently knock down MDC1.Recombined plasmid containing MDC1 was transiently transfected into RBE and Huh28 cells for over-expression of MDC1.Real time quantitative PCR(qPCR)and Western blotting were adopted to verify the effectiveness of MDC1 knockdown or overexpression.The proliferation of CCA cells was measured via CCK-8 and cell colony formation assays.Transwell and Invasion assays were used to detect cell migration and invasion while flow cytometry assays were employed to detect cell cycle and apoptosis.Gene set enrichment analysis(GSEA)was conducted to investigate the pathways which were significantly associated with MDC1,and the expression of p53 downstream protein was verified by Western blotting assay.Co-immunoprecipitation(Co-IP)assays were used to verify the interactions between MDC1 and p53.Flow cytometry and Western blotting assays were performed to find out whether MDC1 promoted cell cycle and cell apoptosis through p53 pathway.Based on The Cancer Genome Altas(TCGA)database,the difference in MDC1 expression levels between CCA and normal tissues was analyzed,and the correlations between the MDC1 expression levels and the clinical prognosis of CCA patients were investigated.Results Knockdown of MDC1 in RBE and Huh28 cells significantly inhibited cells proliferation,migration and invasion,significantly decreased the proportion of cells in S phase,and significantly increased the proportion of cells in G0/G1 phase and apoptosis rate while overexpression of MDC1 could significantly promote cell proliferation,migration and invasion,significantly increase the proportion of cells in S phase,and significantly decrease the proportion of cells in G0/G1 phase and apoptosis rate.It was found that MDC1 interacted with p53 in RBE and Huh28 cells,and MDC1 significantly down-regulated the expressions of p53,p-p53(Ser-15),BAX,PUMA and p21,but significantly up-regulated the expression of Bcl-2,which in turn promoted the tumorigenesis of CCA.MDC1 was up-regulated in CCA tissues compared to the normal tissues,and the high expressions of MDC1 were significantly associated with poor clinical outcomes of CCA patients.Conclusion MDC1 promotes the development of CCA by suppressing the p53 pathway,and MDC1 may be a candidate marker for the poor prognosis in CCA.

Objective : To explore the effect of hydroxy⁃carboxylic acid receptor 2 (HCAR2) on erythroid differen⁃ tiation of human chronic myeloid leukemia K562 cells under hypoxia . Methods : The cells were cultured in medium containing hemin to compare the ability of K562 cells to differentiate into erythroid cells under normoxia/hypoxia conditions . Then the expression of HCAR2 was interfered with genetic methods to knockdown or overexpress it in K562 cells , respectively . Benzidine staining , RT⁃qPCR , Western blot and flow cytometry were used to detect the role of HCAR2 in the erythroid differentiation of K562 promoted by hypoxia . Results : On day 1 , 2 , 3 after differentiation , the expression level of HCAR2 and the erythroid differentiation， the expression level of HCAR2 and the erythroid differentiation ability of K562 cells increased gradually with time , and hypoxia enhanced the above phenotypes compared with normoxia . In HCAR2⁃silenced K562 cells , erythroid cells was reduced and the expression of erythroid differentiation markers CD235a and γ⁃globin decreased . Simultaneously , the proportion of double⁃positive cells expressing erythroid cell surface molecules CD71 and CD235a was lower than that of the control group . On the contrary , the overexpression of HCAR2 in K562 cells increased erythroid cells generation as well as elevated the expression levels of CD235a and γ⁃globin . In addition , the proportion of CD71 /CD235a double⁃positive cells also increased in HCAR2⁃overexpressed K562 cells . Conclusion HCAR2 mediates hypoxia in promoting the erythroid differentiation of K562 cells .

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.

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.

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.

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 .

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.

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.
DNA Copy Number Variations ; Genetic Predisposition to Disease ; Humans