Advances on molecular mechanism of hepatitis B virus-induced hepatocellular carcinoma / 浙江大学学报·医学版

The pathogenesis of hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC） is complicated with the crosstalk of multiple factors and the multi-step processes. The main mechanisms underlying the HBV-induced HCC include:①integration of HBV DNA into the host hepatocyte genome to alter gene function at the insertion site，resulting in host genome instability and expression of carcinogenic truncated proteins;②HBV gene mutations at S，C，and X coding regions in the genome;③HBV X gene-encoded HBx protein activates proto-oncogenes and inhibits tumor suppressor genes，leading to the HCC occurrence. In this article，the recent research progress on the molecular mechanism of HBV-induced HCC is comprehensively reviewed，so as to provide insights into the prevention，early prediction and postoperative adjuvant therapy of HCC.

Research progress on molecular mechanism of hepatitis B virus reactivation after liver transplantation / 器官移植

Liver transplantation is the most effective method for hepatitis B-related liver failure, liver cirrhosis and hepatocellular carcinoma. However, the reactivation of hepatitis B virus (HBV) after liver transplantation is not conducive to the recovery of liver function and leads to poor clinical prognosis. The prevention and treatment of HBV reactivation is currently the focus of research by physicians and surgeons. The current viral suppression strategies can not completely eradicate HBV nor completely prevent the recurrence of HBV infection in the future. This article aims to explore the molecular mechanism of HBV reactivation after liver transplantation, in order to more effectively prevent the recurrence of hepatitis B after liver transplantation.

Mechanism relevant to hepatocellular carcinoma occurrence after negative conversion of viral DNA in treatment of chronic hepatitis B patients with nucleos(t)ide drugs / 中华肝脏病杂志

Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and most of the patients have a background of chronic HBV infection. Nucleos(t)ide drugs (NAs) are currently recommended by major guidelines as a first-line treatments for chronic hepatitis B. However, it is still clinically possible to observe that some patients who have acquired virological response (HBV DNA below the lower detection limit) after NAS treatment progress to HCC, and its mechanism of development is still unclear. In this review, the mechanism relevant to HCC progression in treatment of chronic hepatitis B patients with NAs is analyzed mainly from the aspects of gene integration and persistent inflammatory injury.

Effect of hepatitis B virus X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B patients complicated with hepatocellular carcinoma / 中华传染病杂志

Objective To investigate the effect of hepatitis B virus (HBV) X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B (CHB) patients complicated with hepatocellular carcinoma (HCC).Methods Eighteen CHB patients complicated with HCC who underwent surgical treatment in Taizhou Enze Medical Center Enze Hospital and Taizhou Central Hospital from July 2015 to June 2017 were enrolled.Samples of carcinoma tissue,para-carcinoma tissue and corresponding normal liver tissue were collected from each case.DNA was extracted from three kinds of tissue samples.HBV-Alu-polymerase chain reaction (PCR) was used to amplify the integrated HBVX fragments and their bilateral flanking sequences in human genomic DNA.The integrated HBV fragments were determined by PCR products sequencing.Protein was extracted from three kinds of tissue samples.The level of expression of ZBTB20 was detected by protein imprinting.Statistical analysis was performed using t test,analysis of variance,and x2 test.Results Among the 18 CHB patients complicated with HCC,integration of HBVX gene was found in 13 carcinoma tissue samples,16 para-carcinoma tissue samples and 9 corresponding normal liver tissue samples.The difference was statistically significant (x2 =6.353,P =0.037).Of the 18 patients,the protein expressions of ZBTB20 in carcinoma tissue,para-carcinoma tissue and corresponding normal tissue were (50.14 ± 11.25)％,(40.71±7.17) ％ and (39.06 ± 5.17) ％,respectively,which was statistically different (F =9.420,P ＜ 0.01).HBVX gene integration was detected at ZBTB20 locus in five patients.The expression levels of ZBTB20 in patients with HBVX gene integration at this locus in carcinoma tissue,para-carcinoma tissue and corresponding,normal liver tissue were all significantly lower than those in patients without HBVX gene integration (carcinoma tissue (37.37±10.30)％ vs (55.06 ± 7.06)％,para-carcinoma tissue (32.06 ± 2.61)％ vs (44.04 ± 5.24)％,corresponding normal tissue (34.66 ±5.59)％ vs (40.76 ±4.04)％,t--4.205,4.821 and 2.589,respectively,all P ＜0.05).Conclusions Incidence of HBVX integration in para-carcinoma tissue is higher than that in carcinoma tissue in CHB patients complicated with HCC.The expression level of ZBTB20 in carcinoma tissue is higher than that in para-carcinoma tissue.Integration of HBVX gene at ZBTB20 locus may decreases the expression of ZBTB20.

Effect of hepatitis B virus X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B patients complicated with hepatocellular carcinoma / 中华传染病杂志

Objective@#To investigate the effect of hepatitis B virus (HBV) X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B (CHB) patients complicated with hepatocellular carcinoma (HCC).@*Methods@#Eighteen CHB patients complicated with HCC who underwent surgical treatment in Taizhou Enze Medical Center Enze Hospital and Taizhou Central Hospital from July 2015 to June 2017 were enrolled. Samples of carcinoma tissue, para-carcinoma tissue and corresponding normal liver tissue were collected from each case. DNA was extracted from three kinds of tissue samples. HBV-Alu-polymerase chain reaction (PCR) was used to amplify the integrated HBVX fragments and their bilateral flanking sequences in human genomic DNA. The integrated HBV fragments were determined by PCR products sequencing. Protein was extracted from three kinds of tissue samples.The level of expression of ZBTB20 was detected by protein imprinting. Statistical analysis was performed using t test, analysis of variance, and χ2 test.@*Results@#Among the 18 CHB patients complicated with HCC, integration of HBVX gene was found in 13 carcinoma tissue samples, 16 para-carcinoma tissue samples and 9 corresponding normal liver tissue samples. The difference was statistically significant (χ2=6.353, P=0.037). Of the 18 patients, the protein expressions of ZBTB20 in carcinoma tissue, para-carcinoma tissue and corresponding normal tissue were (50.14±11.25)%, (40.71±7.17)% and (39.06±5.17)%, respectively, which was statistically different (F=9.420, P<0.01). HBVX gene integration was detected at ZBTB20 locus in five patients. The expression levels of ZBTB20 in patients with HBVX gene integration at this locus in carcinoma tissue, para-carcinoma tissue and corresponding, normal liver tissue were all significantly lower than those in patients without HBVX gene integration (carcinoma tissue (37.37±10.30)% vs (55.06±7.06)%, para-carcinoma tissue (32.06±2.61)% vs (44.04±5.24)%, corresponding normal tissue (34.66±5.59)% vs (40.76±4.04)%, t=4.205, 4.821 and 2.589, respectively, all P<0.05).@*Conclusions@#Incidence of HBVX integration in para-carcinoma tissue is higher than that in carcinoma tissue in CHB patients complicated with HCC.The expression level of ZBTB20 in carcinoma tissue is higher than that in para-carcinoma tissue. Integration of HBVX gene at ZBTB20 locus may decreases the expression of ZBTB20.

Diabetes mellitus tipo 2 - a relação genética-nutrientes / Diabetes mellitus type 2 - the genetic-nutrients approach

Advances in genetic research have provided an insight on the interactions between nutrients or bioactive compounds in food and genes, giving rise to a series of new possibilities in the practice of nutrition science. It has long been recognized that the so-called non-communicable chronic diseases have an intrinsic relationship with the eating habits of the individual. Changes in eating patterns caused by nutritional transition favor the spread of these diseases. Diabetes mellitus type 2 is characterized by its increasing incidence worldwide and also for its high morbidity and mortality. This type of diabetes can be understood as a result of the combination of genetic and environmental factors, and food plays an important role among them. Nowadays, genes related to some forms of monogenic diabetes are known. However, the most common types show a polygenic feature, and few genes associated in a reproducible manner in population studies are known. The importance of environmental factors in modulating the clinical expression of the disease is clear in polygenic forms of type 2 diabetes. The aim of this study was to describe the indications in scientific literature for the interaction of food and its components with candidate genes involved in the pathophysiology of type 2 diabetes mellitus.

Los avances en la investigación genética proporcionaron un mejor conocimiento de las interacciones entre los nutrientes y compuestos bioactivos de los alimentos y los genes, dando lugar a una serie de nuevas posibilidades en la práctica de la Ciencia de la Nutrición. Desde hace tiempo se sabe que las llamadas enfermedades crónicas no transmisibles tienen una relación intrínseca con los hábitos alimentarios de las personas. Los cambios en los hábitos alimentarios provocados por la transición nutricional favorecen la propagación de esas enfermedades. La diabetes mellitus tipo 2 se caracteriza por su elevada incidencia en todo el mundo y también por su alta morbilidad y mortalidad. Este tipo de diabetes puede ser entendido como el resultado de la combinación de factores genéticos y ambientales, entre los cuales podemos destacar la alimentación. En la actualidad se conocen algunos genes que están vinculados a las formas monogénicas de diabetes. Las formas más comunes de la enfermedad, sin embargo, tienen un carácter poligénico y se conocen pocos genes que estén asociados de manera reproducible en estudios poblacionales. En las formas poligénicas de diabetes tipo 2 es clara la importancia de los factores ambientales en la modulación de la expresión clínica de la enfermedad. El objetivo de este estudio fue describir lo que la literatura científica viene indicando con relación a la interacción entre los alimentos y sus componentes con los genes candidatos involucrados en la fisiopatología de la diabetes mellitus tipo 2.

Avanços nas pesquisas genéticas permitiram um maior conhecimento sobre interações entre nutrientes ou compostos bioativos presentes nos alimentos e genes, surgindo assim uma série de novas possibilidades na prática da ciência da nutrição. Há muito já se reconhece que as chamadas doenças crônicas não transmissíves possuem uma intrínseca relação com o hábito alimentar do indivíduo. Mudanças no padrão alimentar acarretadas pela transição nutricional favorecem a disseminação dessas doenças. O diabetes mellitus tipo 2 caracteriza-se por sua incidência crescente em todo o mundo e também por sua elevada morbimortalidade. Esse tipo de diabetes pode ser compreendido como resultado da associação de fatores genéticos e ambientais, entre os quais a alimentação merece destaque. Atualmente, são conhecidos alguns genes relacionados às formas monogênicas de diabetes. As formas mais comuns da doença, no entanto, apresentam caráter poligênico e, nesse caso, são conhecidos poucos genes associados de maneira reprodutível em estudos populacionais. Nas formas poligênicas do diabetes tipo 2, fica clara a importância dos fatores ambientais na modulação da expressão clínica da doença. O objetivo deste trabalho foi descrever o que a literatura científica vem determinando para a questão da interação de alimentos e seus componentes com os genes candidatos envolvidos na fisiopatologia do diabetes mellitus tipo 2.

Transgene elimination in genetically modified dry bean and soybean lines

Transgene elimination is a poorly studied phenomenon in plants. We made genetic and molecular studies of a transgenic dry bean line immune to bean golden mosaic geminivirus and a soybean line. In both lines, the transgenes were stable during the vegetative phase but were eliminated during meiosis. Due to its potential biotechnological value, this transgenic line was micropropagated by grafting and the vegetative copies were studied for more than two years. More than 300 plants of progeny were obtained during this period, demonstrating that the phenomenon of elimination was consistently repeated and offering an opportunity for detailed study of transgene elimination, including the characterization of the integration sites. Cloning and sequencing of the transgenic loci, reciprocal crosses to untransformed plants, genomic DNA blots, and GUS assays were performed in the transgenic lines. Based on the molecular and genetic characterization, possible mechanisms involved in transgene elimination include intrachromosomal recombination, genetic instability resulting from the tissue culture manipulations, and co-elimination of transgenes, triggered by a process of genome defense.

Analysis 0f existing condition 0f human papillomaVirus DNA in tongue Cancer / 吉林大学学报(医学版)

Objective:To find out the existing pattern of HPV16 in tongue cancer cell and to analyze itsrole in carcinogenesis of tongue cancer. Methods :Southern blot hybridization was used to detect the HPV16sequence and its existing condition in 20 cases of fresh human tongue cancers. Results:HPV16 DNA se-quence in 5 cases of 20 tongue cancers was detected. And HPV16 DNA existed in tongue cancer cell in non-integration pattern. Conclusion:HPV16 was involved in carcinogenesis of tongue cancer through interactionof HPV gene products rather than its integration with genome of target cell.