Insulin Resistance: From Mechanisms to Therapeutic Strategies

Insulin resistance is the pivotal pathogenic component of many metabolic diseases, including type 2 diabetes mellitus, and is defined as a state of reduced responsiveness of insulin-targeting tissues to physiological levels of insulin. Although the underlying mechanism of insulin resistance is not fully understood, several credible theories have been proposed. In this review, we summarize the functions of insulin in glucose metabolism in typical metabolic tissues and describe the mechanisms proposed to underlie insulin resistance, that is, ectopic lipid accumulation in liver and skeletal muscle, endoplasmic reticulum stress, and inflammation. In addition, we suggest potential therapeutic strategies for addressing insulin resistance.

Prevalence of respiratory virus infection with regard to age, sex, and seasonality factors: A single center experience against children hospitalized during the 10 years

PURPOSE: It is well known that respiratory viral infection has epidemiological characteristics, including season. This study aimed to investigate the patterns of the prevalence of common respiratory viruses during a period of 10 years with regard to age, sex, and season in Korean children. METHODS: From June 2006 to November 2016, we obtained 11,798 specimens from patients aged less than 18 years who were admitted with lower respiratory infections. Ten respiratory viruses were detected using multiplex reverse transcription-polymerase chain reaction. RESULTS: Of 11,798 specimens, at least 1 virus was detected in 4,845 (41.1%). Respiratory syncytial virus (RSV, 18.9%) was the most common virus detected, followed by human rhinovirus (HRV, 14.8%), adenovirus (9.5%), and human bocavirus (HBoV, 7.4%). The detection rate of HRV was higher in male subjects (male 60.0% vs. female 40.0%, P=0.004), but the other viruses had no significant differences with regard to sex. The subjects who were positive for RSV test were youngest (median, 10.5 months; interquartile range, 3.0–25.0 months), followed by human coronavirus (median, 13.0 months), HRV (median, 14 months), and parainfluenza (median, 14 months). HBoV was most commonly detected in spring (29.3%), enterovirus in summer (25.8%), HRV in fall (22.6%), and RSV in October and winter (22.6%). CONCLUSION: We found that the prevalence of respiratory viruses in Korean children during a period of 10 years was associated with age, sex, and season when the infection occurred. Further nationwide data is warranted to infer clinical implication of our results.

Allergen sensitization and vitamin D status in young Korean children with urticaria

PURPOSE: Urticaria is a common disorder, with a lifetime incidence of approximately 15%–20% of the general population. It is difficult to differentiate urticaria in children because of the similarity in symptoms between acute and chronic urticaria. There is also a lack of studies between vitamin D known as an important role in the immune system and urticaria in children. The present study aimed to assess the characteristics and allergen sensitization of young children diagnosed with urticaria and to evaluate the relationship between their vitamin D status and urticaria. METHODS: We retrospectively reviewed medical records of 218 children diagnosed as having urticaria at CHA and Myongji Hospitals between April 2013 and December 2014. The results of questionnaires and laboratory tests, including specific IgE and serum 25-hydroxy vitamin D concentrations were obtained. RESULTS: Of 218 patients, 118 (54%) were positive for at least 1 allergen and there was no significant difference in the prevalence of sensitization between the acute and chronic urticaria groups. However, the prevalence of polysensitization and sensitization of house dust mites was significantly higher in the chronic urticaria group than in the acute urticaria group (P=0.011 and P=0.029, respectively). Among the urticaria symptoms, an itching sensation was more associated with insufficient vitamin D status in children with urticaria (P=0.034). CONCLUSION: Our results demonstrated that children with chronic urticaria have a higher prevalence of sensitization to house dust mites and polysensitization. Further studies will need to determine whether the supply of vitamin D can improve itching sensation in urticaria children with an insufficient vitamin D status.

Functional Profiling of Human MeCP2 by Automated Data Comparison Analysis and Computerized Expression Pathway Modeling / 대한의료정보학회지

OBJECTIVES: Methyl-CpG binding protein 2 (MeCP2) is a ubiquitous epigenetic factor that represses gene expression by modifying chromatin. Mutations in the MeCP2 gene cause Rett syndrome, a progressive neurodevelopmental disorder. Recent studies also have shown that MeCP2 plays a role in carcinogenesis. Specifically, functional ablation of MeCP2 suppresses cell growth and leads to the proliferation of cancer cells. However, MeCP2's function in adult tissues remains poorly understood. We utilized a weight matrix-based comparison software to identify transcription factor binding site (TFBS) of MeCP2-regulated genes, which were recognized by cDNA microarray analysis. METHODS: MeCP2 expression was silenced using annealed siRNA in HEK293 cells, and then a cDNA microarray analysis was performed. Functional analysis was carried out, and transcriptional levels in target genes regulated by MeCP2 were investigated. TFBS analysis was done within genes selected by the cDNA microarray analysis, using a weight matrix-based program and the TRANSFAC 6.0 database. RESULTS: Among the differentially expressed genes with a change in expression greater than two-fold, 189 genes were up-regulated and 91 genes were down-regulated. Genes related to apoptosis and cell proliferation (JUN, FOSL2, CYR61, SKIL, ATF3, BMABI, BMPR2, RERE, and FALZ) were highly up-regulated. Genes with anti-apoptotic and anti-proliferative functions (HNRPA0, HIS1, and FOXC1) were down-regulated. Using TFBS analysis within putative promoters of novel candidate target genes of MeCP2, disease-related transcription factors were identified. CONCLUSIONS: The present results provide insights into the new target genes regulated by MeCP2 under epigenetic control. This information will be valuable for further studies aimed at clarifying the pathogenesis of Rett syndrome and neoplastic diseases.

Functional Profiling of Human MeCP2 by Automated Data Comparison Analysis and Computerized Expression Pathway Modeling / 대한의료정보학회지

OBJECTIVES: Methyl-CpG binding protein 2 (MeCP2) is a ubiquitous epigenetic factor that represses gene expression by modifying chromatin. Mutations in the MeCP2 gene cause Rett syndrome, a progressive neurodevelopmental disorder. Recent studies also have shown that MeCP2 plays a role in carcinogenesis. Specifically, functional ablation of MeCP2 suppresses cell growth and leads to the proliferation of cancer cells. However, MeCP2's function in adult tissues remains poorly understood. We utilized a weight matrix-based comparison software to identify transcription factor binding site (TFBS) of MeCP2-regulated genes, which were recognized by cDNA microarray analysis. METHODS: MeCP2 expression was silenced using annealed siRNA in HEK293 cells, and then a cDNA microarray analysis was performed. Functional analysis was carried out, and transcriptional levels in target genes regulated by MeCP2 were investigated. TFBS analysis was done within genes selected by the cDNA microarray analysis, using a weight matrix-based program and the TRANSFAC 6.0 database. RESULTS: Among the differentially expressed genes with a change in expression greater than two-fold, 189 genes were up-regulated and 91 genes were down-regulated. Genes related to apoptosis and cell proliferation (JUN, FOSL2, CYR61, SKIL, ATF3, BMABI, BMPR2, RERE, and FALZ) were highly up-regulated. Genes with anti-apoptotic and anti-proliferative functions (HNRPA0, HIS1, and FOXC1) were down-regulated. Using TFBS analysis within putative promoters of novel candidate target genes of MeCP2, disease-related transcription factors were identified. CONCLUSIONS: The present results provide insights into the new target genes regulated by MeCP2 under epigenetic control. This information will be valuable for further studies aimed at clarifying the pathogenesis of Rett syndrome and neoplastic diseases.