Stomach adenocarcinoma (STAD) is the fifth most prevalent cancer and the third leading cause of cancer-related death in the world and is more common in Asia than in most Western countries. There is an urgent need to i...Stomach adenocarcinoma (STAD) is the fifth most prevalent cancer and the third leading cause of cancer-related death in the world and is more common in Asia than in most Western countries. There is an urgent need to identify potential novel oncogenes and tumor suppressor genes, and biomarkers for STAD. 6652 differentially expressed genes were identified between STAD and normal samples based on the transcriptome data analysis of the TCGA and GEO databases. 13 key modules were identified in STAD by WGCNA analysis. 293 potential STAD associated genes were identified from intersection by Venn Diagram. The 293 intersected genes were enriched in cell cortex and infection by GO and KEGG analysis. 10 hub genes were identified from PPI and Cytoscape analyses of the intersected genes. KLF4/CGN low and SHH/LIF high expression were associated with short overall survival of Asian STAD patients. Bioinformatics analysis revealed potential novel tumor suppressors (KLF4/CGN), oncogenes (SHH/LIF) and biomarkers for diagnosis, therapy and prognosis of STAD, specifically for Asian patients.展开更多
Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious...Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious cell culture protein 34.5 (ICP34.5) and latency-associated transcript (LAT) genes are closely related to virus selective infection and latent infection. Their engineering is essential for constructing efficient and safe oHSV. We summarized the mechanisms of ICP34.5 and LAT in the course of HSV-1 infection and reviewed the engineered oHSVs. We are aimed to provide an insight in developing oHSV in the future.展开更多
Glutamate dehydrogenase(GDH)plays an important role in the ammonium assimilation and nitrogen metabolism by catalyzing the reversible oxidative deamination of L-glutamate toα-ketoglutarate.In the present study,the po...Glutamate dehydrogenase(GDH)plays an important role in the ammonium assimilation and nitrogen metabolism by catalyzing the reversible oxidative deamination of L-glutamate toα-ketoglutarate.In the present study,the potential functions of GDH in response to heat stre ss were explored in the scleractinian coral Pocillopora damicornis(designated as PdGDH).The cDNA of PdGDH contained an open reading frame of 1611 bp encoding a polypeptide of 536 amino acids,which exhibited the highest sequence identity to GDH of Stylophora pistillata(96%identity),and the deduced PdGDH protein was predicted to contain one GdhA domain(from Val95 to Tyr525).The recombinant protein of PdGDH(rPdGDH)was expressed in Escherichia coli BL21(DE3)-Transetta,and its catalytic activity was measured under different temperatures,pH conditions and epigallocatechin-3-gallate(EGCG,a GDH inhibitor)concentrations.The purified rPdGDH only used reduced coenzyme nicotinamide adenine dinucleotide(NADH)as coenzyme,and its highe st activity was observed at 35℃and pH 7.5,re spectively.The rPdGDH activity was negatively correlated with the concentration of EGCG,and was inhibited by more than half(65%,P<0.05)at 10mol/L EGCG.No significant alteration of PdGDH mRNA expression was detected at 12 h after exposure to heat and ammonium(P>0.05).Furthermore,the activities of NADH-GDH in the scleractinian coral P.damicornis increased significantly at 12 h after the heat and ammonium stress,and the NADH-GDH activity in the heat stress group(32.66 U/mg,P<0.05)was significantly higher than that in the heat and ammonium stress group(11.26 U/mg).These results collectively suggested that PdGDH,as a homologue of glutamate dehydrogenase in the scleractinian coral P.damicornis,could respond to heat stress at the protein level,which would have ability to further promote ammonium assimilation to increase the heat acclimatization of the coral-Symbiodiniaceae symbiotic association.展开更多
Herpes simplex virus (HSV) infection in the human body can be latent in neurons for long time and be reactivated leading to recurrence at high rate. Currently there is no effective clinical strategy for the prevention...Herpes simplex virus (HSV) infection in the human body can be latent in neurons for long time and be reactivated leading to recurrence at high rate. Currently there is no effective clinical strategy for the prevention and treatment of the disease relapse. HSV LAT gene is expressed in large quantities and lytic genes are turned off leading to HSV latency. Disruption of the gene expression is thought to cause HSV reactivation and disease relapse. To reveal the essence of HSV latency and reactivation, we summarized and innovatively classified the role, mechanism and transcriptional regulation of LAT in HSV latency and reactivation. This review may have important implications for future studies on HSV latency and reactivation, HSV disease prevention and treatment, and safer and more effective oncolytic HSVs (oHSVs).展开更多
Herpes simplex virus (HSV) is an enveloped, double-stranded DNA virus that has been used with modification as oncolytic viruses (OVs) against a number of tumor types. OVs represent a new class of therapeutic agents th...Herpes simplex virus (HSV) is an enveloped, double-stranded DNA virus that has been used with modification as oncolytic viruses (OVs) against a number of tumor types. OVs represent a new class of therapeutic agents that promote anti-tumour responses through a dual mechanism of action that is dependent on selective tumor cell killing and the induction of systemic anti-tumour immunity. Among OVs, HSVs preferentially replicate in and lyse cancer cells, leading to in situ autovaccination, adaptive anti-virus and anti-tumor immunity. Suppression of antitumor immunity after OV therapy has been observed and the molecular and cellular mechanisms of action are recently reported. ICP47, a small protein produced by the herpes simplex virus, is considered as an important factor in the evasion of cellular immune responses in HSV-infected cells. Therefore, reviewing the research status of ICP47 is certainly helpful to improve the anti-tumor effect of oncolytic HSVs (oHSVs). Here, this review will focus on the following contents: 1) Anti-tumor mechanism of OVs;2) Functions of early HSV genes;3) The mechanism of immune escape of ICP47;4) Recombinant HSV against cancer;5) The functional verification of ICP47 deletion. This review highlights the current understanding of recombinant HSVs against cancers.展开更多
文摘Stomach adenocarcinoma (STAD) is the fifth most prevalent cancer and the third leading cause of cancer-related death in the world and is more common in Asia than in most Western countries. There is an urgent need to identify potential novel oncogenes and tumor suppressor genes, and biomarkers for STAD. 6652 differentially expressed genes were identified between STAD and normal samples based on the transcriptome data analysis of the TCGA and GEO databases. 13 key modules were identified in STAD by WGCNA analysis. 293 potential STAD associated genes were identified from intersection by Venn Diagram. The 293 intersected genes were enriched in cell cortex and infection by GO and KEGG analysis. 10 hub genes were identified from PPI and Cytoscape analyses of the intersected genes. KLF4/CGN low and SHH/LIF high expression were associated with short overall survival of Asian STAD patients. Bioinformatics analysis revealed potential novel tumor suppressors (KLF4/CGN), oncogenes (SHH/LIF) and biomarkers for diagnosis, therapy and prognosis of STAD, specifically for Asian patients.
文摘Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious cell culture protein 34.5 (ICP34.5) and latency-associated transcript (LAT) genes are closely related to virus selective infection and latent infection. Their engineering is essential for constructing efficient and safe oHSV. We summarized the mechanisms of ICP34.5 and LAT in the course of HSV-1 infection and reviewed the engineered oHSVs. We are aimed to provide an insight in developing oHSV in the future.
基金Supported by the Major Science and Technology Program of Hainan Province (No. ZDKJ2019011)the ISF-NSFC Joint Scientifi c Research Program (No. 42161144006 or 3511/21)+1 种基金the National Natural Science Foundation of China (Nos. 31772460, 42076145)the Hainan Provincial Natural Science Foundation of China (Nos. 2019RC067, 420CXTD432)
文摘Glutamate dehydrogenase(GDH)plays an important role in the ammonium assimilation and nitrogen metabolism by catalyzing the reversible oxidative deamination of L-glutamate toα-ketoglutarate.In the present study,the potential functions of GDH in response to heat stre ss were explored in the scleractinian coral Pocillopora damicornis(designated as PdGDH).The cDNA of PdGDH contained an open reading frame of 1611 bp encoding a polypeptide of 536 amino acids,which exhibited the highest sequence identity to GDH of Stylophora pistillata(96%identity),and the deduced PdGDH protein was predicted to contain one GdhA domain(from Val95 to Tyr525).The recombinant protein of PdGDH(rPdGDH)was expressed in Escherichia coli BL21(DE3)-Transetta,and its catalytic activity was measured under different temperatures,pH conditions and epigallocatechin-3-gallate(EGCG,a GDH inhibitor)concentrations.The purified rPdGDH only used reduced coenzyme nicotinamide adenine dinucleotide(NADH)as coenzyme,and its highe st activity was observed at 35℃and pH 7.5,re spectively.The rPdGDH activity was negatively correlated with the concentration of EGCG,and was inhibited by more than half(65%,P<0.05)at 10mol/L EGCG.No significant alteration of PdGDH mRNA expression was detected at 12 h after exposure to heat and ammonium(P>0.05).Furthermore,the activities of NADH-GDH in the scleractinian coral P.damicornis increased significantly at 12 h after the heat and ammonium stress,and the NADH-GDH activity in the heat stress group(32.66 U/mg,P<0.05)was significantly higher than that in the heat and ammonium stress group(11.26 U/mg).These results collectively suggested that PdGDH,as a homologue of glutamate dehydrogenase in the scleractinian coral P.damicornis,could respond to heat stress at the protein level,which would have ability to further promote ammonium assimilation to increase the heat acclimatization of the coral-Symbiodiniaceae symbiotic association.
文摘Herpes simplex virus (HSV) infection in the human body can be latent in neurons for long time and be reactivated leading to recurrence at high rate. Currently there is no effective clinical strategy for the prevention and treatment of the disease relapse. HSV LAT gene is expressed in large quantities and lytic genes are turned off leading to HSV latency. Disruption of the gene expression is thought to cause HSV reactivation and disease relapse. To reveal the essence of HSV latency and reactivation, we summarized and innovatively classified the role, mechanism and transcriptional regulation of LAT in HSV latency and reactivation. This review may have important implications for future studies on HSV latency and reactivation, HSV disease prevention and treatment, and safer and more effective oncolytic HSVs (oHSVs).
文摘Herpes simplex virus (HSV) is an enveloped, double-stranded DNA virus that has been used with modification as oncolytic viruses (OVs) against a number of tumor types. OVs represent a new class of therapeutic agents that promote anti-tumour responses through a dual mechanism of action that is dependent on selective tumor cell killing and the induction of systemic anti-tumour immunity. Among OVs, HSVs preferentially replicate in and lyse cancer cells, leading to in situ autovaccination, adaptive anti-virus and anti-tumor immunity. Suppression of antitumor immunity after OV therapy has been observed and the molecular and cellular mechanisms of action are recently reported. ICP47, a small protein produced by the herpes simplex virus, is considered as an important factor in the evasion of cellular immune responses in HSV-infected cells. Therefore, reviewing the research status of ICP47 is certainly helpful to improve the anti-tumor effect of oncolytic HSVs (oHSVs). Here, this review will focus on the following contents: 1) Anti-tumor mechanism of OVs;2) Functions of early HSV genes;3) The mechanism of immune escape of ICP47;4) Recombinant HSV against cancer;5) The functional verification of ICP47 deletion. This review highlights the current understanding of recombinant HSVs against cancers.
