Cytomegalovirus (CMV) is a common viral pathogen that influences the outcome of liver transplantation. In addition to the direct effects of CMV syndrome and tissue-invasive diseases, CMV is associated with an increase...Cytomegalovirus (CMV) is a common viral pathogen that influences the outcome of liver transplantation. In addition to the direct effects of CMV syndrome and tissue-invasive diseases, CMV is associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. Risk factors for CMV disease are often interrelated, and include CMV D+/R-serostatus, acute rejection, female gender, age, use of high-dose mycophenolate mofetil and prednisone, and the overall state of immunity. In addition to the role of CMV-specif ic CD4+ and CD8+ T lymphocytes, there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis. In one study, liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher levels of CMV replication and clinical disease. Because of the direct and indirect adverse effects of CMV disease, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component in improving the outcome of liver transplantation. In the majority of transplant centers, antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-). However, the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease. In several prospective and retrospective studies, the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention and novel drugs with unique modes of action are needed. Currently, a randomized controlled clinical trial is being performed comparing the effi cacy and safety of maribavir, a novel benzimidazole riboside, and oral ganciclovir as prophylaxis against primary CMV disease in liver transplant recipients. The treatment of CMV disease consists mainly of intravenous (IV) ganciclovir, and if feasible, a reduction in the degree of immunosuppression. A recent controlled clinical trial demonstrated that valganciclovir is as effective and safe as IV ganciclovir for the treatment of CMV disease in solid organ (including liver) transplant recipients. In this article, the author reviews the current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.展开更多
AIM： To explore the possibility of repression of chloromycetin （Cm） acyl transferase by using external guided sequence （EGS） in order to converse the clinical E coli isolates from Cm- resistant to Cm- sensitive. ...AIM： To explore the possibility of repression of chloromycetin （Cm） acyl transferase by using external guided sequence （EGS） in order to converse the clinical E coli isolates from Cm- resistant to Cm- sensitive. METHODS： EGS directed against chloromycetin acetyl transferase gene （cat） was cloned to vector pEGFP-C1 which contains the kanamycin （Kin） resistance gene. The recombinant plasmid pEGFP-C1＋EGScatl＋cat2 was constructed and the blank vector without EGS fragment was used as control plasmids. By using the CaCl2 transformation method, the recombinant plasmids were introduced into the clinically isolated Cm resistant but Km sensitive E coli strains. Transformants were screened on LB agar plates containing Kin. Extraction of plasmids and PCR were applied to identify the positive clones. The growth curve of EGS transformed bacteria cultured in broth with Cm resistance was determined by using spectrophotometer at A600. Drug sensitivity was tested in solid culture containing Cm by using KB method. RESULTS： Transformation studies were carried out on 16 clinically isolated Cm-resistant （250 μg/mL of Cm） E colistrains by using pEGFP-C1-EGScatlcat2 recombinant plasmid. Transformants were screened on LB-agar plates containing Km after the transformation using EGS. Of the 16 tested strains, 4 strains were transformed successfully. Transformants with EGS plasmid showed growth inhibition when grown in liquid broth culture containing 200 μg/mL of Cm. In drug sensitivity test, these strains were sensitive to Cm on LB-agar plates containing 200 μg/mL of Cm. Extraction of plasmids and PCR amplification showed the existence of EGS plasmids in these four transformed strains. These results indicated that the Cat of the four clinical isolates had been suppressed and the four strains were converted to Cm sensitive ones. CONCLUSION： The EGS directed against Cat is able to inhibit the expression of Cat, and hence convert Cm- resistant bacteria to Cm-sensitive ones. Thus, the EGS has the capability of converting the phenotype of clinical drug-resistant isolates strains to drug-sensitive ones.展开更多
Coccolithophorid is unicellular marine microalgae with a global distribution in temperate and sub-temperate oceanic regions and has the ability to produce ＇the coccoliths＇. It is considered to be the second most pro...Coccolithophorid is unicellular marine microalgae with a global distribution in temperate and sub-temperate oceanic regions and has the ability to produce ＇the coccoliths＇. It is considered to be the second most productive calcifying organism on earth and becoming an important factor in the global carbonate cycle. Emiliania huxleyi is one of the only two bloom-forming coccolithophores and becomes a species crucial to the study of global biogeochemical cycles and climate modeling. Coccolithoviruse is a recently discovered group of viruses infecting the marine coceolithophorid E. huxleyi. They are a major cause of coceolithophore bloom termination, and DMSP concentration is increasing in the process of viral lysis. Phylogenetic evidences support that some genes are functional both in E. huxleyi and its virus （EhV）. Horizontal gene transfer （HGT） of multiple functionally coupled enzymes occurs in E. huxleyi and its DNA virus EhV has been confirmed, which contributes to the diversification and adaptation of plankton in the oceans and also critically regulates virus-host infection by allowing viruses to control host metabolic pathways for their repli- cation. Therefore, it is of particular interest to understand this host-virus interaction. On this issue, we have made a minireview of coeeolithoviruses focusing on the basic characteristics, phylogenesis, horizontal gene transfer and the interaction between the host and its viruses, as well as its important role in global biogeochemical cycling.展开更多
The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an exp...The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an expressive percentage of patients achieving long term survival with anti-CTLA4 and anti-PD1 checkpoint inhibitors. Of note, there is a considerable amount of patients excluded from the checkpoint blockade trials because of comorbidities like chronic viral infections. A precaution to avoid autoimmune induced hepatitis rendered HBV （hepatitis B virus） and HCV （hepatitis C virus） infected patients usually ineligible, but real life data in those patients, who are getting treatment despite of that, is pointing toward the feasibility and safety of immunotherapy in this context. To ilustrate that, we report the case of a metastatic non-BRAF mutated melanoma patient with HCV chronic infection and a surprising benefit derived from ipilimumab and pembrolizumab for his latter condition.展开更多
文摘Cytomegalovirus (CMV) is a common viral pathogen that influences the outcome of liver transplantation. In addition to the direct effects of CMV syndrome and tissue-invasive diseases, CMV is associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. Risk factors for CMV disease are often interrelated, and include CMV D+/R-serostatus, acute rejection, female gender, age, use of high-dose mycophenolate mofetil and prednisone, and the overall state of immunity. In addition to the role of CMV-specif ic CD4+ and CD8+ T lymphocytes, there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis. In one study, liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher levels of CMV replication and clinical disease. Because of the direct and indirect adverse effects of CMV disease, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component in improving the outcome of liver transplantation. In the majority of transplant centers, antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-). However, the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease. In several prospective and retrospective studies, the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention and novel drugs with unique modes of action are needed. Currently, a randomized controlled clinical trial is being performed comparing the effi cacy and safety of maribavir, a novel benzimidazole riboside, and oral ganciclovir as prophylaxis against primary CMV disease in liver transplant recipients. The treatment of CMV disease consists mainly of intravenous (IV) ganciclovir, and if feasible, a reduction in the degree of immunosuppression. A recent controlled clinical trial demonstrated that valganciclovir is as effective and safe as IV ganciclovir for the treatment of CMV disease in solid organ (including liver) transplant recipients. In this article, the author reviews the current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.
基金Supported by the National Natural Science Foundation of China,No. 39570846
文摘AIM： To explore the possibility of repression of chloromycetin （Cm） acyl transferase by using external guided sequence （EGS） in order to converse the clinical E coli isolates from Cm- resistant to Cm- sensitive. METHODS： EGS directed against chloromycetin acetyl transferase gene （cat） was cloned to vector pEGFP-C1 which contains the kanamycin （Kin） resistance gene. The recombinant plasmid pEGFP-C1＋EGScatl＋cat2 was constructed and the blank vector without EGS fragment was used as control plasmids. By using the CaCl2 transformation method, the recombinant plasmids were introduced into the clinically isolated Cm resistant but Km sensitive E coli strains. Transformants were screened on LB agar plates containing Kin. Extraction of plasmids and PCR were applied to identify the positive clones. The growth curve of EGS transformed bacteria cultured in broth with Cm resistance was determined by using spectrophotometer at A600. Drug sensitivity was tested in solid culture containing Cm by using KB method. RESULTS： Transformation studies were carried out on 16 clinically isolated Cm-resistant （250 μg/mL of Cm） E colistrains by using pEGFP-C1-EGScatlcat2 recombinant plasmid. Transformants were screened on LB-agar plates containing Km after the transformation using EGS. Of the 16 tested strains, 4 strains were transformed successfully. Transformants with EGS plasmid showed growth inhibition when grown in liquid broth culture containing 200 μg/mL of Cm. In drug sensitivity test, these strains were sensitive to Cm on LB-agar plates containing 200 μg/mL of Cm. Extraction of plasmids and PCR amplification showed the existence of EGS plasmids in these four transformed strains. These results indicated that the Cat of the four clinical isolates had been suppressed and the four strains were converted to Cm sensitive ones. CONCLUSION： The EGS directed against Cat is able to inhibit the expression of Cat, and hence convert Cm- resistant bacteria to Cm-sensitive ones. Thus, the EGS has the capability of converting the phenotype of clinical drug-resistant isolates strains to drug-sensitive ones.
基金funded by the Chinese Public Science and Technology Research Funds Projects of Ocean (No. 201305027)the National Natural Science Foundation of China (Nos. 40930847, 41376119)+1 种基金Funds of China Southern Oceano-graphic Research Center (No. 14GZP71NF35)Funds of Provincial Key Laboratory of Food Microbiology and Enzyme Engineering (No. M20140910)
文摘Coccolithophorid is unicellular marine microalgae with a global distribution in temperate and sub-temperate oceanic regions and has the ability to produce ＇the coccoliths＇. It is considered to be the second most productive calcifying organism on earth and becoming an important factor in the global carbonate cycle. Emiliania huxleyi is one of the only two bloom-forming coccolithophores and becomes a species crucial to the study of global biogeochemical cycles and climate modeling. Coccolithoviruse is a recently discovered group of viruses infecting the marine coceolithophorid E. huxleyi. They are a major cause of coceolithophore bloom termination, and DMSP concentration is increasing in the process of viral lysis. Phylogenetic evidences support that some genes are functional both in E. huxleyi and its virus （EhV）. Horizontal gene transfer （HGT） of multiple functionally coupled enzymes occurs in E. huxleyi and its DNA virus EhV has been confirmed, which contributes to the diversification and adaptation of plankton in the oceans and also critically regulates virus-host infection by allowing viruses to control host metabolic pathways for their repli- cation. Therefore, it is of particular interest to understand this host-virus interaction. On this issue, we have made a minireview of coeeolithoviruses focusing on the basic characteristics, phylogenesis, horizontal gene transfer and the interaction between the host and its viruses, as well as its important role in global biogeochemical cycling.
文摘The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an expressive percentage of patients achieving long term survival with anti-CTLA4 and anti-PD1 checkpoint inhibitors. Of note, there is a considerable amount of patients excluded from the checkpoint blockade trials because of comorbidities like chronic viral infections. A precaution to avoid autoimmune induced hepatitis rendered HBV （hepatitis B virus） and HCV （hepatitis C virus） infected patients usually ineligible, but real life data in those patients, who are getting treatment despite of that, is pointing toward the feasibility and safety of immunotherapy in this context. To ilustrate that, we report the case of a metastatic non-BRAF mutated melanoma patient with HCV chronic infection and a surprising benefit derived from ipilimumab and pembrolizumab for his latter condition.
