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Acute Myeloid Leukemia (AML) is a highly lethal blood cancer arising due to aberrant differentiation of haematopoietic stem cells. Here we obtained 3D genome organization maps by Hi-C in the CD34+ haematopoietic stem cells from three healthy individuals and eight individuals with AML, and found that AML have increased loops to oncogenes compared with normal CD34+ cells. The MEIS1 oncogenic transcription factor is regulated by a Frequently Interacting Region (FIRE). This FIRE is only present in normal bone marrow samples, and four of eight AML sample. FIRE presence is associated with MEIS1 expression. CRISPR excision of a FIRE boundary led to loss of MEIS1 and reduced cell growth. Moreover, MEIS1 can bind to the promoter of HOXA9, and HOXA9 shows gain of Acute Myeloid Leukemia-specific super-enhancers that loop to the HOXA9 promoter.SignificanceWe found that Acute Myeloid Leukemias have more chromatin loops to oncogenes compared with normal blood stem cells. We identified heterogeneity in chromatin interactions at oncogenes, and heterogeneity in super-enhancers that loop to oncogenes, as two key epigenetic mechanisms that underlie MEIS1 and HOXA9 oncogene expression respectively.

To examine the effect of subcutaneous injection of insulin-like growth factor-1 (IGF-1) on the expression of the amyloid protein (Aβ1–40), α-secretase (ADAM10), β-secretase (BACE1), and γ-secretase (PS1) in APP/PS1 double transgenic mice. APP/PS1 double transgenic mice and wild-type mice were divided into wild-type group, wild-type therapy group, transgenome group, and transgenic therapy group. Subcutaneous injection of IGF-1 (50 μg/kg day) was administered once daily to the wild-type therapy group and transgenic therapy group for 8 weeks, respectively. The expression of the Aβ1–40 in the cortex and hippocampus was detected by immunohistochemistry 8 weeks after administration. The levels of Aβ1–40, DAM10, BACE1, and PS1 were analysed by Western blot. The expression of the Aβ1–40 in the cortex of the gene therapy group was significantly lower than that of the transgenome group (p

Periodontitis is a highly prevalent infectious disease associated genetically with coronary heart disease (CHD). The effects of proprotein convertase subtilisin/kexin type 9 (PCSK9), a critical regulator of CHD, on periodontitis have not been studied to date. Here, we found that PCSK9 expression was increased in periodontitis patients and Porphyromonas gingivalis (Pg)-infected mice. Loss of PCSK9 attenuated Pg-induced periodontal bone loss in mice. First, PCSK9 deficiency reduced the release of inflammation-associated cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin 1β, in vitro and in vivo. Second, its deficiency enhanced Pg and endotoxin clearance during Pg invasion in part by upregulating CD36 and low-density lipoprotein receptor (LDLR), respectively. However, after berberine treatment, periodontal bone regeneration in the PCSK9 knockout group was significantly lower than that in wild-type. This was because PCSK9 overexpression promoted osteogenic differentiation of periodontal ligament stem cells (PDLCs) prechallenged by TNF-α. Furthermore, PCSK9 could rescue PDLC osteogenesis by repressing the NF-κB signaling pathway by interacting with TRAF2. These results suggest that PCSK9 may be a potent drug target for treating periodontitis.

Background: Coffee is a popular beverage in Korea recent years. The purpose of this study was to investigate the relationship between coffee consumption and the risk of metabolic syndrome in Korean adults based on the 2010 Korean National Health and Nutrition Examination Survey (KNHANES V-1). Methods: Dietary intake status and the factors of metabolic syndrome were assessed. Three groups (no coffee consumption, moderate intake, and high intake) were divided into tertile according to black coffee cream (include brewed coffee) consumption per day. Results: Our results showed that the Tertile 3 group consumed more calories from fat, and niacin was higher than in the Tertile 1 and Tertile 2 group. INQ for protein and vitamin B1 was significantly higher in no coffee consumption group than the other groups and in Tertile 3 exhibited significantly higher niacin intake. The subjects in Tertile 3 showed significantly higher consumption in grain and oil intake, and Tertile 1 group showed higher consumption in milk and dairy products. In the logistic regression analysis, adjusting for sex, age, energy intake, smoking, and drinking, being in the high coffee consumption group (Tertile 3) was significantly and inversely associated with abdominal obesity (OR = 0.76, CI = 0.71–0.82), hypertension (OR = 0.70, CI = 0.54–0.87), high glucose(OR = 0.71, CI = 0.61–0.86). However, no significant association was found between coffee consumption and metabolic syndrome. Conclusion: Coffee consumption has not a considerably relationship with nutrient intake. Appropriate consumption of coffee may have potentially helpful effects on certain metabolic risk factors, such as abdominal obesity, hypertension, and high glucose. Keywords: Coffee consumption, Nutrient intake, INQ, Metabolic syndrome, KNHANES

The purpose of this research was to investigate the relationship between white rice consumption and dietary intake, the risk of metabolic syndrome in Korean based on (1998), (2007~2009), (2013) KNHANES. This study included 25,799 subjects who were age 10 or over. Three groups(low, medium, high) were divided according to white rice consumption (per day). In the low group, the meat and oil intake were significantly higher than the high group. In the survey year, the BMI, waist circumstances, hypertriglyceridemia and fasting blood glucose in the high group were higher than other groups, however the and survey year showed no significant results. In the survey year the risk of waist circumstances was higher in the high white rice consumption group and also had high risk with hypertriglyceridemia. Since the lower white rice consumption in than survey year we found no significant results. But in the 6th survey year with the lowest white rice consumption the risk of high diastolic pressure was reduced in high group. Because continuously reduced white rice consumption meantime showed more intake of meat and oil, it can be concluded that defensive effects with the Korean health.

Background: Several studies have previously focused on associations between the (GT)n repeat polymorphism of the heme oxygenase-1 (HO-1) gene promoter region and risk of cancers, but results are complex. We conducted the present meta-analysis to integrate relevant findings and evaluate the association between HO-1 (GT)n repeat polymorphism and cancer susceptibility. Materials and Methods: Published literature was retrieved from the PubMed/MEDLINE, EMBASE and ISI Web of Science databases before November 2013. For all alleles and genotypes, odds ratios were pooled to assess the strength of the associations using either fixed-effects or random-effects models according to heterogeneity. Subgroup analysis was conducted according to ethnicity and histopathology. Results: A total of 10 studies involving 2,367 cases and 2,870 controls were identified. The results showed there was no association between HO-1 (GT)n repeat polymorphism and the cancer risk both at the allelic and genotypic level. However, in the stratified analysis, we observed an increased risk of squamous cell carcinoma in persons carrying the LL genotype and the LL+LS genotype as compared with those carrying the SS genotype. When the LS and SS genotypes were combined, the odds ratio for squamous cell carcinoma in LL-genotype carriers, were also significantly increased. No publication bias was observed. Conclusions: The LL genotype and L-allele carrying genotypes (LL+LS) of HO-1 (GT)n repeat polymorphism are potential genetic factors for developing squamous cell carcinoma. More large and well-designed studies are required for further validations.

Background. Studies on the effect of intensive insulin therapy (IIT) in septic patients with hyperglycemia have given inconsistent results. The primary purpose of this meta-analysis was to evaluate whether it is effective in reducing mortality.Methods. We searched PubMed, Embase, the Cochrane Library, clinicaltrials.gov, and relevant reference lists up to September 2013 and including randomized controlled trials that compared IIT with conventional glucose management in septic patients. Study quality was assessed using the Cochrane Risk of Bias Tool. And our primary outcome measure was pooled in the random effects model.Results. We identified twelve randomized controlled trials involving 4100 patients. Meta-analysis showed that IIT did not reduce any of the outcomes: overall mortality (risk ratio [RR] = 0.98, 95% CI [0.85, 1.15],P=0.84), 28-day mortality (RR = 0.66, 95% CI [0.40, 1.10],P=0.11), 90-day mortality (RR = 1.10, 95% CI [0.97, 1.26],P=0.13), ICU mortality (RR = 0.94, 95% CI [0.77, 1.14],P=0.52), hospital mortality (RR = 0.98, 95% CI [0.86, 1.11],P=0.71), severity of illness, and length of ICU stay. Conversely, the incidence of hypoglycemia was markedly higher in the IIT (RR = 2.93, 95% CI [1.69, 5.06],P=0.0001).Conclusions. For patients with sepsis, IIT and conservative glucose management show similar efficacy, but ITT is associated with a higher incidence of hypoglycemia.

BACKGROUND A model of simulated Alzheimer's disease (AD) induced by aggregated amyloid protein (Abeta(1-40)) was built in Wistar rats to observe the behavioral and pathological changes of Abeta(1-40) and the effect of hypodermic insulin injected on the function of study and memory and the expression of Abeta(1-40) from the CA1 area of the hippocampus. METHODS Experimental groups were as follows: contrast, simulated AD model, contrast of Nacl, and insulin treated. The simulated AD model was built by microinjection of aggregated Abeta(1-40) at the CA1 area of the hippocampus, and was hypodermically injected with 0.9% NaCl (1 ml/kg) and insulin (0.1 U/kg) separately the next day. Two weeks after the modeling, the four groups were tested with water maze about the study and memory function of rats. Three weeks after the injection, the expression of Abeta(1-40) at the CA1 area of the hippocampus was examined by pathological tests (HE, Congo red) and immunohistochemical methods. RESULTS The study and memory abilities of rats were ameliorated significantly by the place navigation test and the spatial probe test after the application of insulin. Insulin could decrease the expression of Abeta(1-40) at the CA1 area of the hippocampus to reduce the pathological damage of Abeta(1-40) to the hippocampal area of rats. CONCLUSIONS The injection of aggregated Abeta(1-40) to the hippocampal area could simulate the behavioral and pathological features of AD such as the difficulty of study and memory and the damage to neurons. Insulin is effective to improve the function of study and memory and amend the pathological damage of simulated AD model rats. The results give a experimental proof of insulin in the clinical treatment of AD.

Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance to chemotherapy. Overexpression of oncogene c-Myc is one of the most frequently encountered events present in ovarian carcinoma. Disrupting the function of c-Myc and its downstream target genes is a promising strategy for cancer therapy. Our objective was to evaluate the potential effects of small-molecule c-Myc inhibitor, 10058-F4, on ovarian carcinoma cells and the underlying mechanisms by which 10058-F4 exerts its actions. Using MTT assay, colony formation, flow cytometry and Annexin V FITC assays, we found that 10058-F4 significantly inhibited cell proliferation of both SKOV3 and Hey ovarian cancer cells in a dose dependent manner through induction of apoptosis and cell cycle G1 arrest. Treatment with 10058-F4 reduced cellular ATP production and ROS levels in SKOV3 and Hey cells. Consistently, primary cultures of ovarian cancer treated with 10058-F4 showed induction of caspase-3 activity and inhibition of cell proliferation in 15 of 18 cases. The response to 10058-F4 was independent the level of c-Myc protein over-expression in primary cultures of ovarian carcinoma. These novel findings suggest that the growth of ovarian cancer cells is dependent upon c-MYC activity and that targeting c-Myc-Max heterodimerization could be a potential therapeutic strategy for ovarian cancer.