Summary: Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomi...Summary: Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C→T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9 % vs 41.7 %, χ2=4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1 %) of SP-B1580-18A/C locus is lower than T allele (70.9 %) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85 % and 15 % respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.展开更多
Summary： This study aimed to investigate the association between surfactant protein B （SP-B） pol- ymorphisms and bronchopulmonary dysplasia （BPD） in Chinese Han infants. We performed a case- control study includi...Summary： This study aimed to investigate the association between surfactant protein B （SP-B） pol- ymorphisms and bronchopulmonary dysplasia （BPD） in Chinese Han infants. We performed a case- control study including 86 infants with BPD and 156 matched controls. Genotyping was performed by sequence specific primer-polymerase chain reaction （PCR） and haplotypes were reconstructed by the fastPHASE software. The results showed that significant differences were detected in the geno- type distribution of C/A-18 and intron 4 polymorphisms of SP-B gene between cases and controls. No significant differences were detected in fhe genotype distribution of C/T1580 or A/G9306 be- tween the two groups. Haplotype analysis revealed that the frequency of A-del-C-A haplotype was higher in case group （0.12 to 0.05, P=0.003）, whereas the frequency of C-inv-C-A haplotype was higher in control group （0.19 to 0.05, P=0.000）. In addition, a significant difference was observed in the frequency of C-inv-T-A haplotype between the two groups. It was concluded that the polymor- phisms of SP-B intron 4 and C/A-18 could be associated with BPD in Chinese Han infants, and the del allele of intron 4 and A allele of C/A-18 might be used as markers of susceptibility in the disease. Haplotype analysis indicated that the gene-gene interactions would play an important part in deter- mining susceptibility to BPD.展开更多
Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a...Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.展开更多
Galectin-related protein B是一种缺乏半乳糖苷结合活性的半乳糖凝集素相关蛋白B。基于NCBI公布的尼罗罗非鱼(Oreochromis niloticus)Galectin-related protein B基因序列设计带酶切位点引物,构建原核表达载体pET-28a-GRPB,将重组质粒...Galectin-related protein B是一种缺乏半乳糖苷结合活性的半乳糖凝集素相关蛋白B。基于NCBI公布的尼罗罗非鱼(Oreochromis niloticus)Galectin-related protein B基因序列设计带酶切位点引物,构建原核表达载体pET-28a-GRPB,将重组质粒导入大肠杆菌,诱导重组质粒的蛋白表达,并对蛋白表达条件进行优化。结果表明:在28℃条件下,IPTG浓度为0.20mmol/L,诱导6h时,诱导重组蛋白的效果最佳;经Western-blot免疫印迹显示,纯化后的重组蛋白能与带HIS标签的单抗特异结合,条带单一,进一步证明该重组蛋白为Galec⁃tin-related protein B蛋白。展开更多
BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorecta...BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.展开更多
Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of ant...Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma.With the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular infection.Herein,we applied a cell-based screening approach to a US Food and Drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(S.Typhimurium).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of S.Typhimurium intracellular proliferation.LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by LPD.In addition,LPD treatment effectively protected against S.Typhimurium infection in Galleria mellonella and mouse models.Thus,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens.Moreover,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.展开更多
Both hepatitis B virus X protein(HBx)and microRNA-221(miR-221)have been implicated in the development of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).The present study demonstrates that HBx promotes HC...Both hepatitis B virus X protein(HBx)and microRNA-221(miR-221)have been implicated in the development of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).The present study demonstrates that HBx promotes HCC cell proliferation via the C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4(CXCL12-CXCR4)axis.We predict that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.Methods:After miR-221 mimic,miR-221 mimic negative control,miR-221 inhibitor,miR-221 inhibitor negative control were transfected into cells,the expression of CXCL12 and miR-221 was detected by qPCR and western blot.Then we constructed a stable HBV-HCC cell line.HBV-HCC cells were injected into the nude mice,thus a HBV-HCC mouse model was constructed.Q-PCR and western blot were used to detect the expression of HBx,miR-221,CXCL12 and CXCR4 in tumor tissues.The expression of CXCL12 was detected by immunohistochemistry,and the expression of CXCR4,CD3 and CD56 was detected by immunofluorescence.The levels of CXCL12,IL-2 and TNF-αin serum of mice were detected by ELISA.Sixty-one patients with HBV-related HCC,61 patients with HBV-related cirrhosis,61 patients with chronic hepatitis B(CHB)and 30 healthy people were enrolled.CXCL12,cytokine levels,and clinicopathological parameters were tested.Results:Hepatitis B virus X protein upregulates the expression of miR-221 and CXCL12 in lentivirus(LV5)-HBx-transfected HepG2 cells.HBx protein promotes HepG2 cell proliferation in vitro.HBx protein promoted tumor growth via the miR-221/CXCL12/CXCR4 pathway in a mouse tumor model.HBx protein upregulated natural killer T cell expression via the CXCR4/CXCL12 pathway to promote tumor growth.The data demonstrated a positive correlation between CXCL12 concentration with Cre levels and Child-Pugh scores.CXCL12 had an inferior diagnostic efficiency compared to IL-2 and IL-6 for HBV-related HCC.Conclusions:We present evidence that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.展开更多
文摘Summary: Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C→T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9 % vs 41.7 %, χ2=4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1 %) of SP-B1580-18A/C locus is lower than T allele (70.9 %) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85 % and 15 % respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.
基金supported by grants from the National Natural Science Foundation of China (Nos. 30872795 and 81170001)
文摘Summary： This study aimed to investigate the association between surfactant protein B （SP-B） pol- ymorphisms and bronchopulmonary dysplasia （BPD） in Chinese Han infants. We performed a case- control study including 86 infants with BPD and 156 matched controls. Genotyping was performed by sequence specific primer-polymerase chain reaction （PCR） and haplotypes were reconstructed by the fastPHASE software. The results showed that significant differences were detected in the geno- type distribution of C/A-18 and intron 4 polymorphisms of SP-B gene between cases and controls. No significant differences were detected in fhe genotype distribution of C/T1580 or A/G9306 be- tween the two groups. Haplotype analysis revealed that the frequency of A-del-C-A haplotype was higher in case group （0.12 to 0.05, P=0.003）, whereas the frequency of C-inv-C-A haplotype was higher in control group （0.19 to 0.05, P=0.000）. In addition, a significant difference was observed in the frequency of C-inv-T-A haplotype between the two groups. It was concluded that the polymor- phisms of SP-B intron 4 and C/A-18 could be associated with BPD in Chinese Han infants, and the del allele of intron 4 and A allele of C/A-18 might be used as markers of susceptibility in the disease. Haplotype analysis indicated that the gene-gene interactions would play an important part in deter- mining susceptibility to BPD.
基金supported by the National Natural Science Foundation of China(grant Nos.30972531 and 81320108026)a project of the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.
文摘Galectin-related protein B是一种缺乏半乳糖苷结合活性的半乳糖凝集素相关蛋白B。基于NCBI公布的尼罗罗非鱼(Oreochromis niloticus)Galectin-related protein B基因序列设计带酶切位点引物,构建原核表达载体pET-28a-GRPB,将重组质粒导入大肠杆菌,诱导重组质粒的蛋白表达,并对蛋白表达条件进行优化。结果表明:在28℃条件下,IPTG浓度为0.20mmol/L,诱导6h时,诱导重组蛋白的效果最佳;经Western-blot免疫印迹显示,纯化后的重组蛋白能与带HIS标签的单抗特异结合,条带单一,进一步证明该重组蛋白为Galec⁃tin-related protein B蛋白。
基金Supported by National Natural Science Foundation of China,No.81760516Natural Science Foundation of Guangxi,China,No.2019GXNSFAA185030+1 种基金Self-Financed Scientific Research Projects of Guangxi Zhuang Autonomous Region Health and Family Planning Commission,China,No.Z20181003Guangxi Medical University Youth Science Fund Project,China,No.GXMUYSF202221.
文摘BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.
基金supported by the National Key Research and Development Program of China(2021YFD1801000)the Natural Science Foundation of China(32373066)+1 种基金the Natural Science Foundation of Jilin Province(20230101142JC)the Fundamental Research Funds for the Central Universities.
文摘Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma.With the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular infection.Herein,we applied a cell-based screening approach to a US Food and Drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(S.Typhimurium).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of S.Typhimurium intracellular proliferation.LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by LPD.In addition,LPD treatment effectively protected against S.Typhimurium infection in Galleria mellonella and mouse models.Thus,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens.Moreover,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.
基金supported by the National Natural Science Foundation of Chongqing,China(No.cstc2019jcyj-msxm0314 of Yishu Tang)the National Key R&D Program of China(No.2017YFC0909902 of Yun Xia)the Natural Science Foundation of China(No.81501818 of Yishu Tang)。
文摘Both hepatitis B virus X protein(HBx)and microRNA-221(miR-221)have been implicated in the development of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).The present study demonstrates that HBx promotes HCC cell proliferation via the C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4(CXCL12-CXCR4)axis.We predict that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.Methods:After miR-221 mimic,miR-221 mimic negative control,miR-221 inhibitor,miR-221 inhibitor negative control were transfected into cells,the expression of CXCL12 and miR-221 was detected by qPCR and western blot.Then we constructed a stable HBV-HCC cell line.HBV-HCC cells were injected into the nude mice,thus a HBV-HCC mouse model was constructed.Q-PCR and western blot were used to detect the expression of HBx,miR-221,CXCL12 and CXCR4 in tumor tissues.The expression of CXCL12 was detected by immunohistochemistry,and the expression of CXCR4,CD3 and CD56 was detected by immunofluorescence.The levels of CXCL12,IL-2 and TNF-αin serum of mice were detected by ELISA.Sixty-one patients with HBV-related HCC,61 patients with HBV-related cirrhosis,61 patients with chronic hepatitis B(CHB)and 30 healthy people were enrolled.CXCL12,cytokine levels,and clinicopathological parameters were tested.Results:Hepatitis B virus X protein upregulates the expression of miR-221 and CXCL12 in lentivirus(LV5)-HBx-transfected HepG2 cells.HBx protein promotes HepG2 cell proliferation in vitro.HBx protein promoted tumor growth via the miR-221/CXCL12/CXCR4 pathway in a mouse tumor model.HBx protein upregulated natural killer T cell expression via the CXCR4/CXCL12 pathway to promote tumor growth.The data demonstrated a positive correlation between CXCL12 concentration with Cre levels and Child-Pugh scores.CXCL12 had an inferior diagnostic efficiency compared to IL-2 and IL-6 for HBV-related HCC.Conclusions:We present evidence that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.
