Objective: To explore the relationship between the insulin resistance and thedefects or mutations or mutations in insulin receptor (InsR)gene. Methods: Using the single-strandconformation polymorphism(SSCP), mutations...Objective: To explore the relationship between the insulin resistance and thedefects or mutations or mutations in insulin receptor (InsR)gene. Methods: Using the single-strandconformation polymorphism(SSCP), mutations and polymorphisms were detected in nine patients withacan-thosis nigricans (AN) and their first degree relatives in exon 17 and 20 of InsR gene. Thepolymorphisms and mutations were confirmed by DNA direct sequencing. Results: Fourteen variant SSCPpat-terns were detected. Direct sequencing revealed seven point mutations and six silentpolymorphisms. Five of the mutations appeared not to be mentioned in the previous literature. Thesemutations were all located within the domain of tyrokinase in InsR. Conclusion: It seem to us thatalmost all the AN patients with severe insulin resistance in this study have mutations in InsRtyrokinase domain.展开更多
To evaluate the role of biofilm formation on the resistance of Helicobacter pylori (H. pylori) to commonly prescribed antibiotics, the expression rates of resistance genes in biofilm-forming and planktonic cells were ...To evaluate the role of biofilm formation on the resistance of Helicobacter pylori (H. pylori) to commonly prescribed antibiotics, the expression rates of resistance genes in biofilm-forming and planktonic cells were compared.METHODSA collection of 33 H. pylori isolates from children and adult patients with chronic infection were taken for the present study. The isolates were screened for biofilm formation ability, as well as for polymerase chain reaction (PCR) reaction with HP1165 and hp1165 efflux pump genes. Susceptibilities of the selected strains to antibiotic and differences between susceptibilities of planktonic and biofilm-forming cell populations were determined. Quantitative real-time PCR (qPCR) analysis was performed using 16S rRNA gene as a H. pylori-specific primer, and two efflux pumps-specific primers, hp1165 and hefA.RESULTSThe strains were resistant to amoxicillin, metronidazole, and erythromycin, except for one strain, but they were all susceptible to tetracycline. Minimum bactericidal concentrations of antibiotics in the biofilm-forming cells were significantly higher than those of planktonic cells. qPCR demonstrated that the expression of efflux pump genes was significantly higher in the biofilm-forming cells as compared to the planktonic ones.CONCLUSIONThe present work demonstrated an association between H. pylori biofilm formation and decreased susceptibility to all the antibiotics tested. This decreased susceptibility to antibiotics was associated with enhanced functional activity of two efflux pumps: hp1165 and hefA.展开更多
Objective To analyze the role of resistin in insulin resistance (IR) through investigating the variation of plasma resistin levels and single-nucleotide polymorphisms (SNPs) in resistin gene 5’ flanking region in str...Objective To analyze the role of resistin in insulin resistance (IR) through investigating the variation of plasma resistin levels and single-nucleotide polymorphisms (SNPs) in resistin gene 5’ flanking region in stroke patients.Methods In 103 atherothrombotic cerebral infarction (ACI) patients, 85 lacunar infarction (LI) patients, 70 intracerebral hemorrhage (ICH) patients, and 86 healthy controls, plasma resistin and insulin levels were measured by ELISA , SNPs in resistin gene 5’ flanking region were detected by PCR and direct DNA sequencing. The subjects’ body height and weight, the body mass index, quantitative insulin sensitivity check index (QUICKI), blood pressure, and the concentration of fasting plasma glucose, triglyceride, total cholesterol, creatinine, low-density lipoprotein, and high-density lipoprotein were also determined. Results QUICKI was significantly lower in the ACI and ICH patients (0.316±0.037 and 0.309±0.032, respectively) than that in the controls (0.342±0.043, P<0.001), while plasma resistin level was significantly higher in the ACI and ICH patients (6.36±3.79 and 7.15±4.27 ng/mL, respectively) than that in the controls (5.28±2.56 ng/mL, P<0.05), but such difference was not observed in the LI patients compared with controls. There was a statistically negative correlation between plasma resistin level with QUICKI (r=-0.228, P<0.001). The distributions of allele and genotype frequencies of resistin gene -420C>G and -537A>C SNPs were not significantly different among the different groups, and those SNPs were not correlated with other clinical and biochemical parameters.Conclusions Plasma resistin is associated with stroke by participating in the development of IR. The SNPs in resistin gene 5’ flanking region has no impact on the plasma resistin level.展开更多
Nonalcoholic steatohepatitis (NASH) is an important indication for liver transplantation in many Western countries. Obesity and insulin resistance are the two most common risk factors for NASH, which can lead to recur...Nonalcoholic steatohepatitis (NASH) is an important indication for liver transplantation in many Western countries. Obesity and insulin resistance are the two most common risk factors for NASH, which can lead to recurrent NASH after liver transplantation. There is currently no approved therapy for NASH, and treatment is directed at risk factor modification and lifestyle changes. Betaine has been used for NASH, with mixed results, and may show promise in conjunction with other agents in clinical trials.展开更多
Glucose homeostasis deficiency leads to a chronic increase in blood glucose concentration. In contrast to physiological glucose concentration, chronic super-physiological glucose concentration negatively affects a lar...Glucose homeostasis deficiency leads to a chronic increase in blood glucose concentration. In contrast to physiological glucose concentration, chronic super-physiological glucose concentration negatively affects a large number of organs and tissues. Glucose toxicity means a decrease in insulin secretion and an increase in insulin resistance due to chronic hyperglycemia. It is now generally accepted that glucose toxicity is involved in the worsening of diabetes by affecting the secretion of B-cells. Several mechanisms have been proposed to explain the adverse effects of hyperglycemia. It was found that persistent hyperglycemia caused the functional decline of neutrophils. Infection is thus the main problem resulting from glucose toxicity in the acute phase. In other words, continued hyperglycemia is a life-threatening risk factor, not only in the chronic but also the acute phase, and it becomes a risk factor for infection, particularly in the perioperative period.展开更多
Adiponectin(APN),a novel hormone/cytokine derived from adipocyte tissue,is involved in various physiological functions. Genetics,nutrition,and adiposity are factors contributing to circulating plasma concentrations of...Adiponectin(APN),a novel hormone/cytokine derived from adipocyte tissue,is involved in various physiological functions. Genetics,nutrition,and adiposity are factors contributing to circulating plasma concentrations of APN.Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers,such as breast and colon cancers,suggesting that APN has a role in tumorigenesis.APN affects insulin resistance,thus further influencing cancer development. Tumor cells may express receptors for APN.Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies.Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy.展开更多
Air pollution is known to be a major risk factor for cardiopulmonary disease, but this is unclear for cardiometabolic disease (e.g.diabetes). This is of considerable public health importance, given the nationwide epid...Air pollution is known to be a major risk factor for cardiopulmonary disease, but this is unclear for cardiometabolic disease (e.g.diabetes). This is of considerable public health importance, given the nationwide epidemic of diabetes, accompanied by severe air pollution, in China. The evidence so far remained inadequate to answer questions of whether individuals with cardiometabolic dysfunctions are susceptible to air pollution and whether air pollution exacerbates diabetes development via certain biological pathways. In this manuscript, we summarize the results and limitations of studies exploring these two topics and elaborate our design of a prospective panel study (SCOPE) as a solution. We assessed and compared the health effect of air pollution among pre-diabetic individuals and matched healthy controls through four repeated clinical visits over 1 year. Comprehensive evaluation was made to both health endpoints and exposure. The primary biomarkers were assessed to reveal the impact on multiple biological pathways, including glycolipid metabolism and insulin resistance, endothelial function, and inflammation. Detailed chemical and size fractional components of particulate matter were measured in this study, along with the application of personal monitors.The work should increase our understanding of how air pollution affects individuals with cardiometabolic dysfunction and the underlying mechanisms.展开更多
To identify novel genes in castration-resistant prostate cancer(CRPC),we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus(GEO).R packages affy and limma were ...To identify novel genes in castration-resistant prostate cancer(CRPC),we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus(GEO).R packages affy and limma were performed to identify differentially expressed genes(DEGs)between primary prostate cancer and CRPC.After that,we performed functional enrichment analysis including gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway.In addition,protein–protein interaction(PPI)analysis was used to search for hub genes.Finally,to validate the significance of these genes,we performed survival analysis.As a result,we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets.Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosteroneregulated sodium reabsorption pathway.PPI network identified hub genes like cortactin-binding protein 2(CTTNBP2),Rho family guanosine triphosphatase(GTPase)3(RND3),protein tyrosine phosphatase receptor-type R(PTPRR),Jagged1(JAG1),and lumican(LUM).Based on PPI network analysis and functional enrichment analysis,we identified two genes(PTPRR and JAG1)as key genes.Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer.In conclusion,PTPRR and JAG1 are key genes in the CRPC,which may serve as promising biomarkers of diagnosis and prognosis of CRPC.展开更多
文摘Objective: To explore the relationship between the insulin resistance and thedefects or mutations or mutations in insulin receptor (InsR)gene. Methods: Using the single-strandconformation polymorphism(SSCP), mutations and polymorphisms were detected in nine patients withacan-thosis nigricans (AN) and their first degree relatives in exon 17 and 20 of InsR gene. Thepolymorphisms and mutations were confirmed by DNA direct sequencing. Results: Fourteen variant SSCPpat-terns were detected. Direct sequencing revealed seven point mutations and six silentpolymorphisms. Five of the mutations appeared not to be mentioned in the previous literature. Thesemutations were all located within the domain of tyrokinase in InsR. Conclusion: It seem to us thatalmost all the AN patients with severe insulin resistance in this study have mutations in InsRtyrokinase domain.
文摘To evaluate the role of biofilm formation on the resistance of Helicobacter pylori (H. pylori) to commonly prescribed antibiotics, the expression rates of resistance genes in biofilm-forming and planktonic cells were compared.METHODSA collection of 33 H. pylori isolates from children and adult patients with chronic infection were taken for the present study. The isolates were screened for biofilm formation ability, as well as for polymerase chain reaction (PCR) reaction with HP1165 and hp1165 efflux pump genes. Susceptibilities of the selected strains to antibiotic and differences between susceptibilities of planktonic and biofilm-forming cell populations were determined. Quantitative real-time PCR (qPCR) analysis was performed using 16S rRNA gene as a H. pylori-specific primer, and two efflux pumps-specific primers, hp1165 and hefA.RESULTSThe strains were resistant to amoxicillin, metronidazole, and erythromycin, except for one strain, but they were all susceptible to tetracycline. Minimum bactericidal concentrations of antibiotics in the biofilm-forming cells were significantly higher than those of planktonic cells. qPCR demonstrated that the expression of efflux pump genes was significantly higher in the biofilm-forming cells as compared to the planktonic ones.CONCLUSIONThe present work demonstrated an association between H. pylori biofilm formation and decreased susceptibility to all the antibiotics tested. This decreased susceptibility to antibiotics was associated with enhanced functional activity of two efflux pumps: hp1165 and hefA.
基金"135 Project"Key Talent Fund of Public Health Department of Jiangsu Province
文摘Objective To analyze the role of resistin in insulin resistance (IR) through investigating the variation of plasma resistin levels and single-nucleotide polymorphisms (SNPs) in resistin gene 5’ flanking region in stroke patients.Methods In 103 atherothrombotic cerebral infarction (ACI) patients, 85 lacunar infarction (LI) patients, 70 intracerebral hemorrhage (ICH) patients, and 86 healthy controls, plasma resistin and insulin levels were measured by ELISA , SNPs in resistin gene 5’ flanking region were detected by PCR and direct DNA sequencing. The subjects’ body height and weight, the body mass index, quantitative insulin sensitivity check index (QUICKI), blood pressure, and the concentration of fasting plasma glucose, triglyceride, total cholesterol, creatinine, low-density lipoprotein, and high-density lipoprotein were also determined. Results QUICKI was significantly lower in the ACI and ICH patients (0.316±0.037 and 0.309±0.032, respectively) than that in the controls (0.342±0.043, P<0.001), while plasma resistin level was significantly higher in the ACI and ICH patients (6.36±3.79 and 7.15±4.27 ng/mL, respectively) than that in the controls (5.28±2.56 ng/mL, P<0.05), but such difference was not observed in the LI patients compared with controls. There was a statistically negative correlation between plasma resistin level with QUICKI (r=-0.228, P<0.001). The distributions of allele and genotype frequencies of resistin gene -420C>G and -537A>C SNPs were not significantly different among the different groups, and those SNPs were not correlated with other clinical and biochemical parameters.Conclusions Plasma resistin is associated with stroke by participating in the development of IR. The SNPs in resistin gene 5’ flanking region has no impact on the plasma resistin level.
文摘Nonalcoholic steatohepatitis (NASH) is an important indication for liver transplantation in many Western countries. Obesity and insulin resistance are the two most common risk factors for NASH, which can lead to recurrent NASH after liver transplantation. There is currently no approved therapy for NASH, and treatment is directed at risk factor modification and lifestyle changes. Betaine has been used for NASH, with mixed results, and may show promise in conjunction with other agents in clinical trials.
文摘Glucose homeostasis deficiency leads to a chronic increase in blood glucose concentration. In contrast to physiological glucose concentration, chronic super-physiological glucose concentration negatively affects a large number of organs and tissues. Glucose toxicity means a decrease in insulin secretion and an increase in insulin resistance due to chronic hyperglycemia. It is now generally accepted that glucose toxicity is involved in the worsening of diabetes by affecting the secretion of B-cells. Several mechanisms have been proposed to explain the adverse effects of hyperglycemia. It was found that persistent hyperglycemia caused the functional decline of neutrophils. Infection is thus the main problem resulting from glucose toxicity in the acute phase. In other words, continued hyperglycemia is a life-threatening risk factor, not only in the chronic but also the acute phase, and it becomes a risk factor for infection, particularly in the perioperative period.
基金supported by grants from the National Health and Medical Research Council of Australia Project Grant ID1006200(LH)Cancer Council of New South Wales IG11- 27(LH)+1 种基金Robert W.Storr Bequest to the University of Sydney (LH)an Australian Postgraduate Award(SO)
文摘Adiponectin(APN),a novel hormone/cytokine derived from adipocyte tissue,is involved in various physiological functions. Genetics,nutrition,and adiposity are factors contributing to circulating plasma concentrations of APN.Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers,such as breast and colon cancers,suggesting that APN has a role in tumorigenesis.APN affects insulin resistance,thus further influencing cancer development. Tumor cells may express receptors for APN.Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies.Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy.
基金supported by the National Natural Science Foundation of China (41421064,21190051, 41121004)the China Postdoc Science Foundation (154248)
文摘Air pollution is known to be a major risk factor for cardiopulmonary disease, but this is unclear for cardiometabolic disease (e.g.diabetes). This is of considerable public health importance, given the nationwide epidemic of diabetes, accompanied by severe air pollution, in China. The evidence so far remained inadequate to answer questions of whether individuals with cardiometabolic dysfunctions are susceptible to air pollution and whether air pollution exacerbates diabetes development via certain biological pathways. In this manuscript, we summarize the results and limitations of studies exploring these two topics and elaborate our design of a prospective panel study (SCOPE) as a solution. We assessed and compared the health effect of air pollution among pre-diabetic individuals and matched healthy controls through four repeated clinical visits over 1 year. Comprehensive evaluation was made to both health endpoints and exposure. The primary biomarkers were assessed to reveal the impact on multiple biological pathways, including glycolipid metabolism and insulin resistance, endothelial function, and inflammation. Detailed chemical and size fractional components of particulate matter were measured in this study, along with the application of personal monitors.The work should increase our understanding of how air pollution affects individuals with cardiometabolic dysfunction and the underlying mechanisms.
文摘To identify novel genes in castration-resistant prostate cancer(CRPC),we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus(GEO).R packages affy and limma were performed to identify differentially expressed genes(DEGs)between primary prostate cancer and CRPC.After that,we performed functional enrichment analysis including gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway.In addition,protein–protein interaction(PPI)analysis was used to search for hub genes.Finally,to validate the significance of these genes,we performed survival analysis.As a result,we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets.Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosteroneregulated sodium reabsorption pathway.PPI network identified hub genes like cortactin-binding protein 2(CTTNBP2),Rho family guanosine triphosphatase(GTPase)3(RND3),protein tyrosine phosphatase receptor-type R(PTPRR),Jagged1(JAG1),and lumican(LUM).Based on PPI network analysis and functional enrichment analysis,we identified two genes(PTPRR and JAG1)as key genes.Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer.In conclusion,PTPRR and JAG1 are key genes in the CRPC,which may serve as promising biomarkers of diagnosis and prognosis of CRPC.