The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide po...The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide polymorphism（SNP） in the response to the treatment of 172 Chinese patients with hepatitis C virus（HCV） chronic infection was analyzed. The results show that the frequencies of major homozygotes（CC） and heterozygotes（CT） of rs12979860 were 0.84 and 0.16, respectively, and the minor homozygotes（TT） wasn’t found in this cohort. A highly significant association was found between the CC genotype and sustained virological response（SVR） in HCV geno type 1 infected patients（P〈0.001） but not in HCV non-genotype 1 infected patients. In addition, a strong association was found between rs12979860 CC genotype and rapid virological response（RVR） in both HCV genotype 1 infected patients（P〈0.001） and non-genotype 1 infected patients（P〈0.001）. Taken together, these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients. Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C（CHC） patients.展开更多
AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 p...AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.展开更多
LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking different...LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking differentiation and promoting proliferation.In addition,it can play a role in epithelial-to-mesenchymal transition by repressing the biogenesis of let-7 microRNAs.In malignancies,LIN28B is frequently overexpressed,which is associated with increased tumor aggressiveness and metastatic properties.In this review,we discuss the molecular mechanisms of LIN28B in promoting tumor progression and metastasis in solid tumor entities and its potential use as a clinical therapeutic target and biomarker.展开更多
AIM: To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response.
Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the product...Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.展开更多
基金Supported by the State Key Disciplines of Clinical Projects and the National Natural Science Foundation of China (No.30970415)
文摘The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide polymorphism（SNP） in the response to the treatment of 172 Chinese patients with hepatitis C virus（HCV） chronic infection was analyzed. The results show that the frequencies of major homozygotes（CC） and heterozygotes（CT） of rs12979860 were 0.84 and 0.16, respectively, and the minor homozygotes（TT） wasn’t found in this cohort. A highly significant association was found between the CC genotype and sustained virological response（SVR） in HCV geno type 1 infected patients（P〈0.001） but not in HCV non-genotype 1 infected patients. In addition, a strong association was found between rs12979860 CC genotype and rapid virological response（RVR） in both HCV genotype 1 infected patients（P〈0.001） and non-genotype 1 infected patients（P〈0.001）. Taken together, these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients. Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C（CHC） patients.
基金Supported by Hamad Hospital-HMC and Qatar UniversityHealth Sciences-Biomedical Labssponsored by HMC
文摘AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.
基金This work was supported by the Fritz Thyssen Foundation(10.21.1.026MN)to L.Meder.
文摘LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking differentiation and promoting proliferation.In addition,it can play a role in epithelial-to-mesenchymal transition by repressing the biogenesis of let-7 microRNAs.In malignancies,LIN28B is frequently overexpressed,which is associated with increased tumor aggressiveness and metastatic properties.In this review,we discuss the molecular mechanisms of LIN28B in promoting tumor progression and metastasis in solid tumor entities and its potential use as a clinical therapeutic target and biomarker.
基金Supported by Department of Medical Science,University of Turin
文摘AIM: To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response.
基金supported by the National Natural Science Foundation of China(No.82103756).
文摘Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.
