Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores ...Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.展开更多
AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic...AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province.展开更多
Background Cellular Repressor of E1A-stimu-lated gene(CREG) is widely expressed in adult tissues such as the brain,heart,lung,liver,intestine and kidney in mice.It is not known whether tissue CREG is decreased in the ...Background Cellular Repressor of E1A-stimu-lated gene(CREG) is widely expressed in adult tissues such as the brain,heart,lung,liver,intestine and kidney in mice.It is not known whether tissue CREG is decreased in the common setting of myocardial infarction which may lead to heart failure.We studied the expression and protein localization of CREG and its main receptor(IFR2R) in a mouse model of myocardial infarction.Methods Male mice were randomized to proximal left anterior descending ligation.The animals were killed on day 1,3,7,14,and 28 after ligation to examine gene expression and protein production of CREG and IGF2R from the infarct,peri-infarct,and contralateral zones of infarcted heart.Results There was decreased CREG mRNA production throughout the myocardium at dav 1,and the expression gradually increased at day 28 after myocardial infarction.The decreased expression of this glycoprotein was not confined strictly to the infarct or peri-infarct zones but also expressed by cardiac myocytes within the myocardium in the contralateral normal zone.Levels of CREG protein in the infarct and peri-infarct zones declined to 1/3- to 1/2-fold of normal levels and declined to 1/2- to 2/3- fold in the contralateral zone.Finally,the expression of the IGF2R mRNA transcripts was downregulated at day 3 and 7 after ligation in the infarct and peri-infarct zones,suggesting that the signal transduction pathways necessary for CREG in the heart remain intact as CREG biosynthesis decreases. Conclusions CREG is constantly present in a model of large myocardial infarction and is decreased at the early stage within the myocardium.The decreased expression of this glycoprotein is not only confined strictly to the infarct or periinfarct zone but also is expressed by cardiac myocytes within the myocardium contralateral to the infarct.Therefore CREG production decreased due to myocardial stress response to injury.展开更多
To construct an expression vector containing the E1 glycoprotein gene of rubella virus for the study on the effect of mutation of the E1 gene glycoprotein and the analysis of phylogenetic differences of sequences, the...To construct an expression vector containing the E1 glycoprotein gene of rubella virus for the study on the effect of mutation of the E1 gene glycoprotein and the analysis of phylogenetic differences of sequences, the gene encoding the E1 envelope glycoprotein was amplified from rubella virus, Jinan strain JR23, by RT-PCR and ligated into PMD-18T vector. The clones that carried the E1 gene were identified after amp r selection and analysis of restriction enzyme digestion. After sequencing this gene was analyzed by Danstar and Winstar programs, and the map of phylogenetic tree was drawn. The clone of E1 glycoprotein was thus constructed. It was found that the sequence differences between JR23 strain and the TCRB strain from Japan and those between JR23 strain and Thomas strain of England were rather small with difference values of 0.9% and 1.2% respectively. Yet those between JR23 strain and BRD2 strain from Beijing and those between JR23 strain and XG379 strain from Hong Kong were comparatively larger with difference values of 7.6% and 7.3% respectively. The sequence of JR23 strain with other strains was less than 3% except the NC strain (3.7%). It concludes that the construction of E1 glycoprotein gene offers an approach to study the relationship between structures and functions of E1 gene and its gene products. In the phylogenetic tree, it shows that there are significant differences in the sequences of rubella virus isolated in China, and this might be helpful to develop an effective subunit vaccine.展开更多
Objectives Phenotypic switching of smooth muscle cells(SMCs) plays a critical role in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD).Accumulating evidence demonstrates(hat a cellular...Objectives Phenotypic switching of smooth muscle cells(SMCs) plays a critical role in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD).Accumulating evidence demonstrates(hat a cellular repressor of E1A-stimulated genes(CREG) plays a role in the maintenance of the mature phenotype of vascular SMCs. The purpose of the present study was to assess the possible association between CREG and CAD in the Han population of North China.Methods The promoter region of CREG by direct sequencing was conducted in 48 subjects.Then SNP rs2995073 and another 4 tagSNPs(rs4657669,rs3767443, rsl6859185,rs3753921) were selected for the association study.All five selected SNPs were determined in 1161 patients with angiographically proven CAD and 960 controls with normal coronary angiograms to investigate the possible involvement of CREG in CAD.Results Genotype frequencies of the five examined polymorphisms were similarly distributed between CAD group and controls(P】0.05).Further haplotype analysis also found no significant differences in the distributions between CAD group and controls(P】0.05). Conclusions This study did not show an association between common variants of CREG and CAD in the northern Chinese Han population.展开更多
AIM:To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS:A total of 104 jaundice patients and 124 community c...AIM:To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS:A total of 104 jaundice patients and 124 community controls were included. Serological analysis was performed by routine enzyme-linked immunosorbent assay, and nucleic acid testing for hepatitis viruses was done by polymerase chain reaction (PCR), followed by PCR direct sequencing for viral genotyping. Cytochrome P450 2E1 (CYP2E1) polymorphism was studied by PCR-restriction fragment length polymorphism. Nitrite and volatile nitrosamines in indigenous foods consumed routinely by the Northeast Indian ethnic population were estimated by Griess’s reagent and GC-MS, respectively.RESULTS: Hepatitis A virus (HAV) infection was predominantly prevalent (36.5%) in our cohort, followed by hepatitis B virus (HBV), hepatitis E virus (HEV) andhepatitis C virus. HBV genotype D and HEV genotype 1 were the most dominant. CYP2E1 c1/c2 genotype frequency was comparatively higher in alcoholic (P<0.0001,OR =30.5) and cryptogenic (P=0.014, OR=8.714) patients, and was associated with significantly higher hepatitis risk (P=0.0.007,OR=6.489). Mutant C allele of Cyp2E1 DraⅠ frequency was comparatively higher in HAV (P=0.006), alcoholic (P =0.003) and cryptogenic (P=0.014) cases, and was associated with overall hepatitis risk (P=0.026, OR=5.083). Indigenous foods, Gundruk, Kharoli, betel leaf and nuts were found to have the highest nitrite content. CONCLUSION: Apart from viral factors, CYP2E1 polymorphism might be associated with increased risk of liver diseases in Northeast India. Indigenous foods that contain nitrite and nitrosamine might be an associated risk factor.展开更多
Rivers can act as reservoirs of highly resistant strains and facilitate the dissemination of resistance, virulence and integron 1 genes. A cross-sectional study was carried out where 318 water samples were collected (...Rivers can act as reservoirs of highly resistant strains and facilitate the dissemination of resistance, virulence and integron 1 genes. A cross-sectional study was carried out where 318 water samples were collected (53 from each site) and from the samples, 318 E. coli isolates were analysed for resistance genes, virulence genes and integron 1 using Polymerase Chain Reaction. 22% of the isolates had blaTEM, 33% had blaCTX-M and 28% had blaCMY. Prevalence of typical Enteropathogenic E. coli strains (carrying both eae and bfp genes) was 5% while the prevalence of atypical Enteropathogenic E. coli (carying only eae) was 1.8%. The prevalence of Enteroaggregative E. coli carrying the aggr genes was 11%. The prevalence of Enterotoxigenic E. coli encoding only lt toxin was 16 (5%) and while those carrying only st toxin was 6.9%. The prevalence of Enteroinvasive E. coli strains encoding as IpaH was 5% while that of strains, adherent invasive E. coli, carrying adherent invasive gene inv was 8.7%. 36% isolates were positive for class 1 integrons which were mostly isolated near the sewage effluent from waste treatment plant. Anthropogenic activities and close proximity to sewage treatment plant were found to play a key role in pollution of water body and accumulation of resistance and virulence genes. These results suggest that waste treatment plant may act as reservoir of resistance, virulence and integron 1 genes and is a potential risk to human and animal health in the region.展开更多
OBJECTIVE: To develop a new kind of vector system called gene-viral vector, which combines the advantages of gene and virus therapies. METHODS: Using recombinant technology, an anti-tumor gene was inserted into the ge...OBJECTIVE: To develop a new kind of vector system called gene-viral vector, which combines the advantages of gene and virus therapies. METHODS: Using recombinant technology, an anti-tumor gene was inserted into the genome of replicative virus specific for tumor cells. The cell killing effect, reporter gene expression of the green fluorescence protein, anti-tumor gene expression of mouse interleukin-12 (mIL-12) and replication of virus were observed by the methods of cell pathology, fluorescence microscopy, ELISA and electron microscopy, respectively. RESULTS: A new kind of gene-viral vector system of adenovirus, in which the E1b-55 kD gene was deleted but the E1a gene was preserved, was constructed. The vector system, like the replicative virus ONYX-015, replicated and proliferated in tumor cells but not in normal ones. Our vector had an advantage over ONYX-015 in that it carried different kinds of anti-tumor genes to enhance its therapeutic effect. The reporter gene expression of the green fluorescence protein in tumor cells was much better than the adenovirus vector employed in conventional gene the rapy, and the expression in our vector system was as low as or even less than that in the conventional adenovirus gene therapy system. Similar results were observed in experiments with this vector system carrying the anti-tumor gene mIL-12. Replication and proliferation of the virus carrying the mIL-12 gene in tumor cells were confirmed by electron microscopy. CONCLUSIONS: Gene-viral vectors are new vectors with an anti-tumor gene inserted into the genome of replicative virus specific for tumor cells. Because of the specific replication and proliferation of the virus in tumor cells, expression of the anti-tumor gene is increased hundreds to thousands of times. This approach takes full advantages of gene therapy and virus therapy to enhance the effect on the tumor. It overcomes the disadvantages of conventional gene therapy, such as low transfer rate, low gene expression, lack of target tropism, and low anti-tumor activity. We believe that this is a promising means for future tumor treatment.展开更多
OBJECTIVE: To clarify the role of these cyclins in human gastric cancer. METHODS: 38 gastric cancer patients, 29 first degree relatives of gastric cancer patients, as well as 18 healthy subjects were included. The mRN...OBJECTIVE: To clarify the role of these cyclins in human gastric cancer. METHODS: 38 gastric cancer patients, 29 first degree relatives of gastric cancer patients, as well as 18 healthy subjects were included. The mRNA expression of cyclins D1, D2, D3 and E in gastric biopsies was evaluated by RT-PCR analysis using specific primers. Histomorphological features such as intestinal metaplasia, atrophy, H. pylori infection and severity of gastritis were determined by the updated Sydney System. RESULTS: Significant mRNA overexpression was found for cyclins D2, D3 and E compared with healthy normal specimen, but cyclin D1 expression was not different between tumor and normal tissues. In addition, cyclin D2 and D3 overexpression was significantly more frequent in first degree relatives than in healthy controls (P展开更多
In this study,we identified the most deleterious nsSNP in RB1 gene through structural and functional properties of its protein (pRB) and investigated its binding affinity with E2F-2.Out of 956 SNPs,we investigated 12 ...In this study,we identified the most deleterious nsSNP in RB1 gene through structural and functional properties of its protein (pRB) and investigated its binding affinity with E2F-2.Out of 956 SNPs,we investigated 12 nsSNPs in coding region in which three of them (SNPids rs3092895,rs3092903 and rs3092905) are commonly found to be damaged by I-Mutant 2.0,SIFT and PolyPhen programs.With this effort,we modeled the mutant pRB proteins based on these deleterious nsSNPs.From a comparison of total energy,stabilizing residues and RMSD of these three mutant proteins with native pRB protein,we identified that the major mutation is from Glutamic acid to Glycine at the residue position of 746 of pRB.Further,we compared the binding efficiency of both native and mutant pRB (E746G) with E2F-2.We found that mutant pRB has less binding affinity with E2F-2 as compared to native type.This is due to sixteen hydrogen bonding and two salt bridges that exist between native type and E2F-2,whereas mutant type makes only thirteen hydrogen bonds and one salt bridge with E2F-2.Based on our investigation,we propose that the SNP with an id rs3092905 could be the most deleterious nsSNP in RB1 gene causing retinoblastoma.展开更多
We cloned and analyzed the two genes of the 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase(HDR) gene family from Huperzia serrate.The two transcripts coding HDR,named Hs HDR1 and Hs HDR2,were discovered in t...We cloned and analyzed the two genes of the 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase(HDR) gene family from Huperzia serrate.The two transcripts coding HDR,named Hs HDR1 and Hs HDR2,were discovered in the transcriptome dataset of H.serrate and were cloned by reverse transcription-polymerase chain reaction(RT-PCR).The physicochemical properties,protein domains,protein secondary structure,and 3D structure of the putative Hs HDR1 and Hs HDR2 proteins were analyzed.The full-length c DNA of the Hs HDR1 gene contained 1431 bp encoding a putative protein with 476 amino acids,whereas the Hs HDR2 gene contained 1428 bp encoding a putative protein of 475 amino acids.These two proteins contained the conserved domain of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase(PF02401),but without the transmembrane region and signal peptide.The most abundant expression of Hs HDR1 and Hs HDR2 was detected in H.serrate roots,followed by the stems and leaves.Our results provide a foundation for exploring the function of Hs HDR1 and Hs HDR2 in terpenoid and sterol biosynthesis in Huperziaceae plants.展开更多
基金Supported by the National High-Level Hospital Clinical Research Fund,No.2022-PUMCH-A-020the Undergraduate Teaching Reform and Innovation Project,No.2022zlgc0108.
文摘Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.
基金Supported by Natural Science Foundation of Fujian Province,China,No.C001009
文摘AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province.
文摘Background Cellular Repressor of E1A-stimu-lated gene(CREG) is widely expressed in adult tissues such as the brain,heart,lung,liver,intestine and kidney in mice.It is not known whether tissue CREG is decreased in the common setting of myocardial infarction which may lead to heart failure.We studied the expression and protein localization of CREG and its main receptor(IFR2R) in a mouse model of myocardial infarction.Methods Male mice were randomized to proximal left anterior descending ligation.The animals were killed on day 1,3,7,14,and 28 after ligation to examine gene expression and protein production of CREG and IGF2R from the infarct,peri-infarct,and contralateral zones of infarcted heart.Results There was decreased CREG mRNA production throughout the myocardium at dav 1,and the expression gradually increased at day 28 after myocardial infarction.The decreased expression of this glycoprotein was not confined strictly to the infarct or peri-infarct zones but also expressed by cardiac myocytes within the myocardium in the contralateral normal zone.Levels of CREG protein in the infarct and peri-infarct zones declined to 1/3- to 1/2-fold of normal levels and declined to 1/2- to 2/3- fold in the contralateral zone.Finally,the expression of the IGF2R mRNA transcripts was downregulated at day 3 and 7 after ligation in the infarct and peri-infarct zones,suggesting that the signal transduction pathways necessary for CREG in the heart remain intact as CREG biosynthesis decreases. Conclusions CREG is constantly present in a model of large myocardial infarction and is decreased at the early stage within the myocardium.The decreased expression of this glycoprotein is not only confined strictly to the infarct or periinfarct zone but also is expressed by cardiac myocytes within the myocardium contralateral to the infarct.Therefore CREG production decreased due to myocardial stress response to injury.
基金This study was supported by grants from the Natural Science Foundationof Shandong Province (No.Q99C10) and Key University Teachers of Educa tion Ministry, China
文摘To construct an expression vector containing the E1 glycoprotein gene of rubella virus for the study on the effect of mutation of the E1 gene glycoprotein and the analysis of phylogenetic differences of sequences, the gene encoding the E1 envelope glycoprotein was amplified from rubella virus, Jinan strain JR23, by RT-PCR and ligated into PMD-18T vector. The clones that carried the E1 gene were identified after amp r selection and analysis of restriction enzyme digestion. After sequencing this gene was analyzed by Danstar and Winstar programs, and the map of phylogenetic tree was drawn. The clone of E1 glycoprotein was thus constructed. It was found that the sequence differences between JR23 strain and the TCRB strain from Japan and those between JR23 strain and Thomas strain of England were rather small with difference values of 0.9% and 1.2% respectively. Yet those between JR23 strain and BRD2 strain from Beijing and those between JR23 strain and XG379 strain from Hong Kong were comparatively larger with difference values of 7.6% and 7.3% respectively. The sequence of JR23 strain with other strains was less than 3% except the NC strain (3.7%). It concludes that the construction of E1 glycoprotein gene offers an approach to study the relationship between structures and functions of E1 gene and its gene products. In the phylogenetic tree, it shows that there are significant differences in the sequences of rubella virus isolated in China, and this might be helpful to develop an effective subunit vaccine.
文摘Objectives Phenotypic switching of smooth muscle cells(SMCs) plays a critical role in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD).Accumulating evidence demonstrates(hat a cellular repressor of E1A-stimulated genes(CREG) plays a role in the maintenance of the mature phenotype of vascular SMCs. The purpose of the present study was to assess the possible association between CREG and CAD in the Han population of North China.Methods The promoter region of CREG by direct sequencing was conducted in 48 subjects.Then SNP rs2995073 and another 4 tagSNPs(rs4657669,rs3767443, rsl6859185,rs3753921) were selected for the association study.All five selected SNPs were determined in 1161 patients with angiographically proven CAD and 960 controls with normal coronary angiograms to investigate the possible involvement of CREG in CAD.Results Genotype frequencies of the five examined polymorphisms were similarly distributed between CAD group and controls(P】0.05).Further haplotype analysis also found no significant differences in the distributions between CAD group and controls(P】0.05). Conclusions This study did not show an association between common variants of CREG and CAD in the northern Chinese Han population.
基金Supported by Gauhati University,Guwahati,Assam,India
文摘AIM:To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS:A total of 104 jaundice patients and 124 community controls were included. Serological analysis was performed by routine enzyme-linked immunosorbent assay, and nucleic acid testing for hepatitis viruses was done by polymerase chain reaction (PCR), followed by PCR direct sequencing for viral genotyping. Cytochrome P450 2E1 (CYP2E1) polymorphism was studied by PCR-restriction fragment length polymorphism. Nitrite and volatile nitrosamines in indigenous foods consumed routinely by the Northeast Indian ethnic population were estimated by Griess’s reagent and GC-MS, respectively.RESULTS: Hepatitis A virus (HAV) infection was predominantly prevalent (36.5%) in our cohort, followed by hepatitis B virus (HBV), hepatitis E virus (HEV) andhepatitis C virus. HBV genotype D and HEV genotype 1 were the most dominant. CYP2E1 c1/c2 genotype frequency was comparatively higher in alcoholic (P<0.0001,OR =30.5) and cryptogenic (P=0.014, OR=8.714) patients, and was associated with significantly higher hepatitis risk (P=0.0.007,OR=6.489). Mutant C allele of Cyp2E1 DraⅠ frequency was comparatively higher in HAV (P=0.006), alcoholic (P =0.003) and cryptogenic (P=0.014) cases, and was associated with overall hepatitis risk (P=0.026, OR=5.083). Indigenous foods, Gundruk, Kharoli, betel leaf and nuts were found to have the highest nitrite content. CONCLUSION: Apart from viral factors, CYP2E1 polymorphism might be associated with increased risk of liver diseases in Northeast India. Indigenous foods that contain nitrite and nitrosamine might be an associated risk factor.
文摘Rivers can act as reservoirs of highly resistant strains and facilitate the dissemination of resistance, virulence and integron 1 genes. A cross-sectional study was carried out where 318 water samples were collected (53 from each site) and from the samples, 318 E. coli isolates were analysed for resistance genes, virulence genes and integron 1 using Polymerase Chain Reaction. 22% of the isolates had blaTEM, 33% had blaCTX-M and 28% had blaCMY. Prevalence of typical Enteropathogenic E. coli strains (carrying both eae and bfp genes) was 5% while the prevalence of atypical Enteropathogenic E. coli (carying only eae) was 1.8%. The prevalence of Enteroaggregative E. coli carrying the aggr genes was 11%. The prevalence of Enterotoxigenic E. coli encoding only lt toxin was 16 (5%) and while those carrying only st toxin was 6.9%. The prevalence of Enteroinvasive E. coli strains encoding as IpaH was 5% while that of strains, adherent invasive E. coli, carrying adherent invasive gene inv was 8.7%. 36% isolates were positive for class 1 integrons which were mostly isolated near the sewage effluent from waste treatment plant. Anthropogenic activities and close proximity to sewage treatment plant were found to play a key role in pollution of water body and accumulation of resistance and virulence genes. These results suggest that waste treatment plant may act as reservoir of resistance, virulence and integron 1 genes and is a potential risk to human and animal health in the region.
文摘OBJECTIVE: To develop a new kind of vector system called gene-viral vector, which combines the advantages of gene and virus therapies. METHODS: Using recombinant technology, an anti-tumor gene was inserted into the genome of replicative virus specific for tumor cells. The cell killing effect, reporter gene expression of the green fluorescence protein, anti-tumor gene expression of mouse interleukin-12 (mIL-12) and replication of virus were observed by the methods of cell pathology, fluorescence microscopy, ELISA and electron microscopy, respectively. RESULTS: A new kind of gene-viral vector system of adenovirus, in which the E1b-55 kD gene was deleted but the E1a gene was preserved, was constructed. The vector system, like the replicative virus ONYX-015, replicated and proliferated in tumor cells but not in normal ones. Our vector had an advantage over ONYX-015 in that it carried different kinds of anti-tumor genes to enhance its therapeutic effect. The reporter gene expression of the green fluorescence protein in tumor cells was much better than the adenovirus vector employed in conventional gene the rapy, and the expression in our vector system was as low as or even less than that in the conventional adenovirus gene therapy system. Similar results were observed in experiments with this vector system carrying the anti-tumor gene mIL-12. Replication and proliferation of the virus carrying the mIL-12 gene in tumor cells were confirmed by electron microscopy. CONCLUSIONS: Gene-viral vectors are new vectors with an anti-tumor gene inserted into the genome of replicative virus specific for tumor cells. Because of the specific replication and proliferation of the virus in tumor cells, expression of the anti-tumor gene is increased hundreds to thousands of times. This approach takes full advantages of gene therapy and virus therapy to enhance the effect on the tumor. It overcomes the disadvantages of conventional gene therapy, such as low transfer rate, low gene expression, lack of target tropism, and low anti-tumor activity. We believe that this is a promising means for future tumor treatment.
文摘OBJECTIVE: To clarify the role of these cyclins in human gastric cancer. METHODS: 38 gastric cancer patients, 29 first degree relatives of gastric cancer patients, as well as 18 healthy subjects were included. The mRNA expression of cyclins D1, D2, D3 and E in gastric biopsies was evaluated by RT-PCR analysis using specific primers. Histomorphological features such as intestinal metaplasia, atrophy, H. pylori infection and severity of gastritis were determined by the updated Sydney System. RESULTS: Significant mRNA overexpression was found for cyclins D2, D3 and E compared with healthy normal specimen, but cyclin D1 expression was not different between tumor and normal tissues. In addition, cyclin D2 and D3 overexpression was significantly more frequent in first degree relatives than in healthy controls (P
文摘In this study,we identified the most deleterious nsSNP in RB1 gene through structural and functional properties of its protein (pRB) and investigated its binding affinity with E2F-2.Out of 956 SNPs,we investigated 12 nsSNPs in coding region in which three of them (SNPids rs3092895,rs3092903 and rs3092905) are commonly found to be damaged by I-Mutant 2.0,SIFT and PolyPhen programs.With this effort,we modeled the mutant pRB proteins based on these deleterious nsSNPs.From a comparison of total energy,stabilizing residues and RMSD of these three mutant proteins with native pRB protein,we identified that the major mutation is from Glutamic acid to Glycine at the residue position of 746 of pRB.Further,we compared the binding efficiency of both native and mutant pRB (E746G) with E2F-2.We found that mutant pRB has less binding affinity with E2F-2 as compared to native type.This is due to sixteen hydrogen bonding and two salt bridges that exist between native type and E2F-2,whereas mutant type makes only thirteen hydrogen bonds and one salt bridge with E2F-2.Based on our investigation,we propose that the SNP with an id rs3092905 could be the most deleterious nsSNP in RB1 gene causing retinoblastoma.
基金supported by the National Nature Science Foundation of China(No.30900113)the Program for Innovative Research Team in the Institute of Medicinal Plant Development(No.IT1304)
文摘We cloned and analyzed the two genes of the 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase(HDR) gene family from Huperzia serrate.The two transcripts coding HDR,named Hs HDR1 and Hs HDR2,were discovered in the transcriptome dataset of H.serrate and were cloned by reverse transcription-polymerase chain reaction(RT-PCR).The physicochemical properties,protein domains,protein secondary structure,and 3D structure of the putative Hs HDR1 and Hs HDR2 proteins were analyzed.The full-length c DNA of the Hs HDR1 gene contained 1431 bp encoding a putative protein with 476 amino acids,whereas the Hs HDR2 gene contained 1428 bp encoding a putative protein of 475 amino acids.These two proteins contained the conserved domain of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase(PF02401),but without the transmembrane region and signal peptide.The most abundant expression of Hs HDR1 and Hs HDR2 was detected in H.serrate roots,followed by the stems and leaves.Our results provide a foundation for exploring the function of Hs HDR1 and Hs HDR2 in terpenoid and sterol biosynthesis in Huperziaceae plants.