Key Points• LIN28B regulates HbF expression in erythroblasts that are cultured from umbilical cord and adult human blood.• LIN28B expression manifested a more fetal-like phenotype among adult human erythroblasts.Reactivation of fetal hemoglobin (HbF) holds therapeutic potential for sickle cell disease and b-thalassemias. In human erythroid cells and hematopoietic organs, LIN28B and its targeted let-7 microRNA family, demonstrate regulated expression during the fetal-toadult developmental transition. To explore the effects of LIN28B in human erythroid cell development, lentiviral transduction was used to knockdown LIN28B expression in erythroblasts cultured from human umbilical cord CD341 cells. The subsequent reduction in LIN28B expression caused increased expression of let-7 and significantly reduced HbF expression. Conversely, LIN28B overexpression in cultured adult erythroblasts reduced the expression of let-7 and significantly increased HbF expression. Cellular maturation was maintained including enucleation. LIN28B expression in adult erythroblasts increased the expression of g-globin, and the HbF content of the cells rose to levels >30% of their hemoglobin. Expression of carbonic anhydrase I, glucosaminyl (N-acetyl) transferase 2, and miR-96 (three additional genes marking the transition from fetal-toadult erythropoiesis) were reduced by LIN28B expression. The transcription factor BCL11A, a well-characterized repressor of g-globin expression, was significantly down-regulated. Independent of LIN28B, experimental suppression of let-7 also reduced BCL11A expression and significantly increased HbF expression. LIN28B expression regulates HbF levels and causes adult human erythroblasts to differentiate with a more fetal-like phenotype. (Blood. 2013;122(6):1034-1041 IntroductionIn humans and some other mammals, the composition of hemoglobin tetramers in erythrocytes switch from fetal hemoglobin (HbF) (a2g2) to adult hemoglobin (HbA) (a2b2) during the last stages of fetal development until early infancy.1 HbF is the most important known modifier of the clinical symptoms for patients with sickle cell disease (SCD) and b-thalassemias, which are among the most common genetic disorders worldwide. 2,3 In patients with SCD, the polymerization of sickle hemoglobin results in erythrocyte deformation and hemolysis.4 SCD patient's clinical outcomes are largely improved by inhibition of the polymerization by HbF. 5 In b-thalassemias, decreased production of b-globin causes imbalanced globin polypeptide chain synthesis, and leads to severe effects on the erythroid cells' maturation and survival. The loss of b-globin expression may be compensated by an increase in HbF production that leads to improvement of the clinical phenotype. 6 The molecular mechanisms underlying the switch from HbF to HbA are still largely unknown. Genome-wide association studies (GWAS) in both normal individuals and patients with b-hemoglobinopathies have identified BCL11A, HSB1L-MYB, and HBB clusters as having an association with the persistence of Hb...

Short (≤ 6 hr) and long (≥ 9 hr) sleep durations are both associated with risk factors for cardiovascular diseases and diabetes, depression, learning problems, accidents and excess mortality. However, little is known about factors associated with sleep duration in Korean adults. This study examined sleep patterns in Korean adults and identified factors associated with short and long sleep durations. This study analyzed cross-sectional data collected from 4,411 Korean adults aged 19 yr and older who participated in a community health survey conducted in Gwangju, Korea. Multinomial logistic regression analysis was used to identify associations between socio-demographic and health-related factors and short or long sleep durations. Of the population, 37.2% and 4.0% reported short and long sleep, respectively. Short sleep was associated with older age, lower levels of income, night or shift work, heavy smoking, and depression or anxiety; long sleep was associated with younger age, being divorced or widowed, heavy smoking, underweight, depression or anxiety, and poorer self-reported health. In conclusion, a relatively high prevalence of short sleep duration is identified in this population of Korean adults. Factors associated with short or long sleep may act as potential confounders of the relationship between sleep duration and health outcomes.

This study was performed to integrate the results of previous studies that investigated the relationship between body mass index (BMI) and prognosis in breast cancer. We reviewed the English literatures using the MEDLINE database from 1966 to 1999. The materials included 12 published articles with a total of 8,029 cases of breast cancer. The effect size was obtained from hazard ratio in each study. Homogeneity test was conducted before the integration of each effect size and the result demonstrated that the studies were heterogeneous. A random effect model was used to integrate the overall effect size. The integrated effect size was 1.56 (95% confidence interval, 1.22-2.00). In addition, publication bias should be accounted for because each published study was asymmetric in shape revealed by funnel plot. These results suggest that BMI have a prognostic significance in breast cancer. We believe that well-designed longitudinal studies, involving a large number of samples are required to resolve these issues.

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This study was performed to evaluate the relation of high-sensitivity C-reactive protein (hsCRP) with several cardiovascular risk factors such as age, blood pressure, smoking habit and serum lipids, body mass index, blood glucose, regular exercise, alcohol drinking, white blood cell counts in a cross-sectional survey. Plasma hsCRP was measured by immunoturbidimetry in 202 subjects, aged over 50 yr, who participated in health-check survey in a rural area of Jeollanamdo, Korea. Plasma hsCRP level was 1.9±3.0 mg/dL. There were significant associations between hsCRP levels and age, white blood cell counts, blood glucose, diastolic blood pressure, HDL-cholesterol, body mass index and smoking status. In stepwise multivariate regression analysis, white blood cell counts, age, blood glucose, smoking status and body mass index were independent correlates of hsCRP levels. In conclusion, plasma hsCRP levels were associated with several cardiovascular risk factors, and these data are compatible with the hypothesis that CRP levels may be a marker for preclinical cardiovascular disease. Further what we need now are prospective studies to evaluate the association of C-reactive protein concentrations with subsequent cardiac events.