Treatment of hypoplastic left heart syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome. METHODS: Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis. RESULTS: Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock-Taussig-Thomas shunt group 1-3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results. CONCLUSIONS: Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.

Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

An 8-week face-split study to evaluate the efficacy of cosmeceuticals using non-invasive bioengineering devices.

BACKGROUND/AIMS: Even with the increasing demand for functional cosmeceuticals in the recent years, objective standard criteria for assessing their efficacy are currently incomplete at best. In this 8-week face-split study, in which we topically applied high-priced cosmeceuticals on one side and more affordable cosmeceuticals on the other side of the face, we compared the efficacy of these two products using non-invasive bioengineering technology. METHODS: We assessed the efficacy of a skin-whitening and an anti-wrinkle cosmeceutical product on 25 and 19 healthy female volunteers, respectively. In a single blind split setting, each participant received an 8-week topical application of high-priced cosmeceuticals to the left side of the face, and cheaper cosmeceuticals to the right side. Then, the subjects' biophysical parameters were measured for an objective evaluation of the results. This was followed by a questionnaire to obtain a subjective assessment. RESULTS: There was no significant difference in the change between the high-priced cosmeceuticals and the more affordable cosmeceuticals. At each measured site, there were variable changes including skin improvement and aggravation at the end of study. The subjective questionnaire demonstrated also that the participants perceived no difference in the efficacy between the two products. CONCLUSIONS: Our results showed that there were no significant differences in the skin biophysical parameters following the application with high-priced functional cosmeceuticals or less expensive cosmeceuticals. The subject failed to differentiate between the two products. The development of objective standard criteria for assessing its efficacy is essential.

A comparison of serum inflammatory cytokines according to phenotype in patients with psoriasis.

BACKGROUND: Plaque-type psoriasis manifests with various morphological phenotypes and different clinical activity over time in the same individual or from one patient to another. Circulating cytokines, especially T-helper (Th) 1- and Th17-related, have been suggested to reflect the inflammatory nature of psoriasis. However, studies regarding cytokine profile according to morphological phenotypes are quite scarce. OBJECTIVES: We sought to analyse the circulating Th1 and Th17 cytokines according to clinical phenotype and investigated the correlation between disease severity [Psoriasis Area and Severity Index (PASI)] and the serum level of inflammatory cytokines. METHODS: Seventy-one patients with psoriasis were divided into two groups according to clinical phenotype: chronic stable (CS) and eruptive inflammatory (EI). Th1- and Th17-derived cytokines were measured using multiplex cytokine assay. RESULTS: It was noted that interleukin (IL)-1 receptor antagonist and IL-17A were elevated in the EI group compared with the CS group. We also noticed that the PASI is relatively well correlated with serum cytokine level in the CS state but not as well in the EI counterpart. CONCLUSIONS: The level of serum inflammatory cytokines differs according to morphological phenotype. Also, the PASI does not seem to be a suitable tool to assess disease severity in patients with psoriasis with EI characteristics.

Neighbourhood characteristics, lifestyle factors, and child development: Secondary analysis of the All our families cohort study.

Background: Neighbourhood characteristics have been found to influence child development, but little is known about lifestyle factors that may moderate this relationship, which can provide modifiable targets for policies and programing. This study investigated the association between neighbourhood characteristics (e.g., deprivation, disorder) during pregnancy and child development at age 5 in relation to various lifestyle factors (e.g., physical activity, parent-child reading, community resource use) during early childhood. Methods: A secondary analysis was conducted using multilevel modeling of data from the All Our Families cohort, recruited in Canada from 2008 to 2010. Participants self-reported on demographics during pregnancy, lifestyle factors at 3 years, and child development at 5 years using the Ages and Stages Questionnaire (ASQ-3). Neighbourhood deprivation was evaluated using the Vancouver Area Deprivation Index (VANDIX), while disorder was measured using police services' community crime reports. Results: Geocoded information was available for 2,444 participants. After adjusting for covariates, multilevel modeling indicated a significant negative association between neighbourhood deprivation and overall child development (b = -.726, 95% CI: -1.344, -.120). Parent-child reading was found to be a significant moderator of the effect of neighbourhood disorder (b = .005, 95% CI: .001, .009). There were no statistically significant moderation effects for physical activity or community resource use. Conclusion: Neighbourhood deprivation during pregnancy is associated with early child development. Parent-child reading may function as a protective factor in the presence of higher neighbourhood disorder. Overall, neighbourhood-level effects should be considered in policies and community programs that promote family and child well-being.

Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism.

INTRODUCTION: Globally, non-alcoholic fatty liver disease (NAFLD) continues to rise and isoflavones exert antisteatotic effects by the regulation of hepatic lipogenesis/insulin resistance or adiposity/a variety of adipocytokines are related to hepatic steatosis. However, there is very little information regarding the potential effects of daidzein, the secondary abundant isoflavone, on NAFLD. Here, we have assessed the hepatic global transcription profiles, adipocytokines and adiposity in mice with high fat-induced NAFLD and their alteration by daidzein supplementation. METHODS: C57BL/6J mice were fed with normal fat (16% fat of total energy), high fat (HF; 36% fat of total energy) and HF supplemented with daidzein (0.1, 0.5, 1 and 2 g per kg diet) for 12 weeks. RESULTS: Daidzein supplementation (≥ 0.5 g per kg diet) reduced hepatic lipid concentrations and alleviated hepatic steatosis. The hepatic microarray showed that daidzein supplementation (1 g per kg diet) downregulated carbohydrate responsive element binding protein, a determinant of de novo lipogenesis, its upstream gene liver X receptor ß and its target genes encoding for lipogenic enzymes, thereby preventing hepatic steatosis and insulin resistance. These results were confirmed by lower insulin and blood glucose levels as well as homeostasis model assessment insulin resistance scores. In addition, daidzein supplementation inhibited adiposity by the upregulation of genes involved in fatty acid ß-oxidation and the antiadipogeneis, and moreover augmented antisteatohepatitic leptin and adiponectin mRNA levels, whereas it reduced the mRNA or concentration of steatotic tumor necrosis factor α and ghrelin. CONCLUSIONS: These findings show that daidzein might alleviate NAFLD through the direct regulation of hepatic de novo lipogenesis and insulin signaling, and the indirect control of adiposity and adipocytokines by the alteration of adipocyte metabolism.

Characteristics of a "rebound" in smoking after a tobacco price increase.

SETTING: In Korea, the price of a pack of cigarettes increased 80% from US$2.2 to US$4 in 2015. The smoking rate decreased in 2015. However, it rebounded in the following year.OBJECTIVE: To evaluate the characteristics associated with this rebound in smoking rate following the price increase.DESIGN: We analysed the KNHANES (Korean National Health and Nutrition Examination Survey) data of 44 015 participants to evaluate current smoking rate and the proportion of smokers planning to quit within 6 months from 2010 to 2016. We also performed focused analysis of 18 303 participants between 2014 and 2016 KNHANES to determine the current smoking rate according to their demographic and socio-economic characteristics.RESULTS: Individuals who were older, female, unemployed, had a low household income or a shorter total smoking period, or smoked less per day were more likely to stop or reduce smoking after the price increase. The current smoking rate increased to 18.8% in 2016 from 17.7% in 2015; this difference was significant in men, those in the lower-middle quartile of household income, those with a middle-school or college education, and those who were employed.CONCLUSION: The rebound in smoking after the price increase was significantly related to the individual's sex, income, education and employment status.

Poor nutritional intake is a dominant factor for weight loss in chronic obstructive pulmonary disease.

Increase in energy expenditure and/or decrease in nutritional intake leads to low body mass index (BMI). The balance between energy expenditure and nutritional intake has rarely been evaluated in a large population of patients with chronic obstructive pulmonary disease (COPD). To evaluate BMI, nutritional intake and physical activity and the association of these factors with the severity of airflow obstruction in COPD patients. We analysed the Korean National Health and Nutrition Examination Survey (KNHANES) data set from 2012 to 2015. Among the 9682 individuals (1601 with COPD and 8081 without COPD) recruited, BMI was lower in COPD patients than in non-COPD participants (males, 23.86 ± 2.76 vs. 24.28 ± 2.80, P < 0.001; females, 23.63 ± 2.94 vs. 23.98 ± 3.10, P < 0.05). As the stage of COPD advanced, BMI, intake of nutrients (food, water and carbohydrates) and total energy levels declined in COPD patients. Total time spent walking in the preceding week decreased with advancing COPD stage in male patients with COPD. COPD severity was an important risk factor for the limitation of physical activity due to respiratory problems (OR 3.92, 95%CI 2.77∼5.34, P < 0.001). Patients with COPD had a low nutritional intake with little physical activity, which worsened with advancing COPD stage. In late-stage COPD, impaired nutritional intake outweighed the decrease in physical activity, resulting in weight loss. .

Combination drug therapy using edaravone and Daio-Orengedoku-to after transient focal ischemia in rats.

In this study, we investigated the effect of Daio-Orengedoku-to (DOT) on ischemic brain damage in a rat model of focal ischemia-reperfusion and attempted to identify synergistic effects for the combination of edaravone and DOT against ischemic insult. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion followed for 22 h. To determine the neuroprotective effect of DOT, it was administered orally just before reperfusion and then 2 h after reperfusion. To examine the effects of combination therapy on survival, rats were divided into groups treated with edaravone, DOT, and edaravone and DOT. Microglial activation, neutrophil infiltration and brain-derived neurotrophic factor (BDNF) expression were examined in surviving animals. Infarct volume was significantly reduced by DOT (100, 200 and 400 mg/kg; P < 0.05), and edaravone plus DOT markedly improved the survival rate after transient ischemia (P = 0.0133). Microglial activation was reduced by edaravone and DOT and their combination (P < 0.05), and neutrophil infiltration was lowered in these groups (P < 0.05). BDNF-positive cells were increased in the combination edaravone and DOT group (P < 0.05). It appears that the neuroprotective mechanisms of combined therapy involve inhibition of microglial activation, reduction of invading neutrophils and enhancement of BDNF expression.

The active site and substrates binding mode of malonyl-CoA synthetase determined by transferred nuclear Overhauser effect spectroscopy, site-directed mutagenesis, and comparative modeling studies.

The active sites and substrate bindings of Rhizobium trifolii molonyl-CoA synthetase (MCS) catalyzing the malonyl-CoA formation from malonate and CoA have been determined based on NMR spectroscopy, site-directed mutagenesis, and comparative modeling methods. The MCS-bound conformation of malonyl-CoA was determined from two-dimensional-transferred nuclear Overhauser effect spectroscopy data. MCS protein folds into two structural domains and consists of 16 alpha-helices, 24 beta-strands, and several long loops. The core active site was determined as a wide cleft close to the end of the small C-terminal domain. The catalytic substrate malonate is placed between ATP and His206 in the MCS enzyme, supporting His206 in its catalytic role as it generates reaction intermediate, malonyl-AMP. These findings are strongly supported by previous biochemical data, as well as by the site-directed mutagenesis data reported here. This structure reveals the biochemical role as well as the substrate specificity that conservative residues of adenylate-forming enzymes have.

Age-related changes of water content in the rat skin.

The water content of the skin is greatly influenced by ground substances, which may be responsible for wrinkling and laxity of the skin accompanying the cutaneous aging. Therefore, water content in the skin is presumed to be a critical determinant in cutaneous aging. This study was aimed at clarifying the change in water content and the content of glycosaminoglycans (GAG) of rat skin in relation to aging. Sprague-Dawley rats were divided into 6 groups: 1-, 3-, 6-, 12-, 18- and 24-month-old groups. Two-to-three grams of skin tissue samples were taken from the back, and a half of sample was dried at 160 degrees C for 30 min with electronic moisture balance, and water content was assessed as decreased weight by heating. To measure change of GAG of the rat skin, another half of samples were extracted with 0.1 M sodium phosphate buffer (pH 7.4 NaPB) and 2 M guanidine-HCl/Tris buffer (pH 7.4). The resultant insoluble pellet was dried at 50 degrees C in a drying over for 72 h after two washings and the dry weight was recorded. The amount of sulfated GAG in the skin extracts was measured by alcian blue precipitation assay, and the amount of uronic acid (UA) was assayed in the skin tissue extracts and the dried skin using the carbazole reaction. The water content of the rat skin decreased with age, and a similar decreasing pattern in the amount of sulfated GAG and UA of the rat skin tissue was observed with aging. One hundred times of UA was obtained in dry rat skin tissue, as compared with that of the skin extracts. In conclusion, there occurs a significant decrease of water content in the aged rat skin, which may be related to the change of GAG with intrinsic aging of the skin.

Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins.

In the present study, we examined whether the bone morphogenetic proteins (BMPs), which are important in the developmental specification of transmitter type in certain classes of neurons, might also play a role in signaling the differentiation of a dopaminergic (DA) phenotype. We found that BMP-2, -4 and -6 were each capable of inducing, in a dose and time dependent manner, moderate levels of the DA enzyme tyrosine hydroxylase (TH) in cultured neurons from the mouse embryonic striatum. In contradistinction to other TH-inducing agents, BMPs initiated de novo TH expression without the required synergy of exogenous growth factors or co-activating substances and in neurons presumably aged (E16) beyond the critical period for induction. However, the appearance of TH in induced cells was short-lived (24 h) and could not be prolonged by repeated supplementation with the BMPs. Inhibitors of the mitogen-activated protein kinase (MAPK/ERK) signaling pathway, PD98059 and apigenin, did not prevent TH induction by BMP-4, as they did other TH inducing agents, indicating that the MAPK/ERK pathway does not mediate BMPs effects on TH expression. We conclude that BMP-2, -4 and -6 can be added to the expanding inventory of agents capable of inducing TH, making them potentially important in the specification of a DA phenotype in stem/precursor cells for the treatment of Parkinson's disease.

Risk of child abuse or neglect in a cohort of low-income children.

The purposes of this research were to identify risk factors for reported child abuse or neglect and to examine the roles of stress and social support in the etiology of child maltreatment. Mothers of newborn infants with biomedical and sociodemographic risk factors were recruited from community and regional hospitals and local health departments in 42 counties of North and South Carolina selected for geographic distribution and for large numbers of such newborns. For every four such mothers, the next mother to deliver an otherwise normal newborn was sought. Mothers were interviewed shortly after giving birth, and state Central Registries of Child Abuse and Neglect were reviewed when each infant was 1 year of age. Eight hundred forty-two of 1,111 recruited mothers were successfully interviewed in their homes between March 1986 and June 1987. Seven hundred forty-nine North Carolina births who resided in the state more than 6 months were eligible for inclusion in the analysis. Logistic regression with backward elimination procedures was used in the analysis. Maternal education (p < .01), number of other dependent children in the home (p < .01), receipt of Medicaid (p < .01), maternal depression (p < .05), and whether the maternal subject lived with her own mother at age 14 years (p < .05) were the best predictors of a maltreatment report. Further examination revealed an interaction effect between stressful life events, as measured by life event scores, and social well-being (p < .01). For children born at risk for social and/or medical problems, extreme low income (participation in public income support programs), low maternal education, maternal depression, the presence of any other young children in the home, and a mother's separation at age 14 years from her own mother significantly predict child maltreatment reports in the first year of life. In addition, stressful life events, even if perceived positively, may increase or decrease the risk of maltreatment reports, depending upon the presence of social support.

Stress, social support, and substantiated maltreatment in the second and third years of life.

OBJECTIVE: The purpose of this research was to determine whether risk factors for a maltreatment report in the first year of life, especially the interaction of life event stress and social support, persist into the second and third years of life. METHOD: Predominantly low income mothers who had been interviewed shortly after the birth of infants in a longitudinal cohort were re-interviewed around the infants' first birthdays, and reports to North Carolina's Central Registry of Child Abuse and Neglect were tracked for substantiated maltreatment reports. RESULTS: Variables significantly associated with a substantiated maltreatment report in the second or third year of life (p < .01) were first year maltreatment reports and participation in Medicaid. Three interactions between a stressful life event indicator variable and a social support indicator variable were significant predictors of substantiated second or third year reports (p < .05). CONCLUSIONS: Even in the presence of significant risk factors from the first year of life, life event stress can increase the risk of a substantiated maltreatment report in the second or third years of life, but social support may moderate the effect of life events.

Fast microtomography using bright monochromatic x-rays.

A fast microtomography system for high-resolution high-speed imaging has been developed using bright monochromatic x-rays at the BL29XU beamline of SPring-8. The shortest scan time for microtomography we attained was 0.25 s in 1.25 µm effective pixel size by combining the bright monochromatic x-rays, a fast rotating sample stage, and a high performance x-ray imaging detector. The feasibility of the tomography system was successfully demonstrated by visualization of rising bubbles in a viscous liquid, an interesting issue in multiphase flow physics. This system also provides a high spatial (a measurable feature size of 300 nm) or a very high temporal (9.8 µs) resolution in radiographs.

Incidence and management of postoperative abdominal bleeding after liver transplantation.

PURPOSE: To assess the incidence and management of postoperative abdominal bleeding after orthotopic liver transplantation (OLT) and to identify risk factors for abdominal bleeding. METHODS: We retrospectively reviewed the medical records of 1039 patients who underwent OLT at our institution from January 2008 to December 2010 seeking to identify subjects with posttransplantation abdominal bleeding, defined as any hemorrhage requiring radiologic intervention or laparotomy within the first month. RESULTS: Among the 1039 patients, 94 (9%) showed abdominal bleeding, occurring at a mean of 6.1 days (range, day 1 to 21 days). Active bleeding was controlled by endovascular interventional techniques (n = 37; 39%), by surgical ligation or vascular reconstruction (n = 43; 46%), or by sequential combinations of endovascular intervention and surgery (n = 14; 15%). The most frequent bleeding sites for radiologic intervention were the right inferior phrenic artery (n = 14), right and left epigastric arteries (n = 7), intercostal artery (n = 5) and right renal capsular artery (n = 4). The most frequent bleeding sites requiring laparotomy were the hepatic artery (n = 9), diaphragm (n = 8), inferior vena cava (n = 5), abdominal drain insertion site (n = 4), portal vein anastomosis site (n = 4), abdominal wall (n = 3), liver graft cut surface (n = 3), hilar plate (n = 3), and greater omentum (n = 3). Bleeding episodes were associated with greater patient age and increased intraoperative blood loss. CONCLUSIONS: The risk of bleeding from coagulopathy and iatrogenic injury is high during the early posttransplantation period. This risk of bleeding can be minimized by meticulous surgical dissection and bleeding control.

Homologous expression and quantitative analysis of T3SS-dependent secretion of TAP-tagged XoAvrBs2 in Xanthomonas oryzae pv. oryzae induced by rice leaf extract.

Xanthomonas oryzae pv. oryzae (Xoo) produces a putative effector, XoAvrBs2. We expressed XoAvrBs2 homologously in Xoo with a TAP-tag at the C-terminus to enable quantitative analysis of protein expression and secretion. Addition of rice leaf extracts from both Xoo-sensitive and Xoo-resistant rice cultivars to the Xoo cells induced expression of the XoAvrBs2 gene at the transcriptional and translational levels, and also stimulated a remarkable amount of XoAvrBs2 secretion into the medium. In a T3SS-defective Xoo mutant strain, secretion of the TAPtagged XoAvrBs2 was blocked. Thus, we elucidated the transcriptional and translational expressions of the XoAvrBs2 gene in Xoo was induced in vitro by the interaction with rice and the induced secretion of XoAvrBs2 was T3SSdependent. It is the first report to measure the homologous expression and secretion of XoAvrBs2 in vitro by rice leaf extract. Our system for the quantitative analysis of effector protein expression and secretion could be generally used for the study of host-pathogen interactions.

Genistein and daidzein repress adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells via Wnt/ß-catenin signalling or lipolysis.

OBJECTIVES: One aspect of the effects of isoflavones against fat deposition might be at least associated with the mechanism by which Wnt/ß-catenin signalling inhibits adipocyte differentiation. However, it remains completely unknown as to whether isoflavones might influence Wnt signalling during commitment of pluripotent mesenchymal stem cells (MSCs) to adipose lineages. In the present study, we have investigated the mechanisms underlying effects of genistein and daidzein, the major soy isoflavones, on anti-adipogenic Wnt/ß-catenin signalling. MATERIALS AND METHODS: Adipose tissue-derived (AD) MSCs were exposed continuously to genistein and daidzein (0.01-100 µm) during adipogenic differentiation (21 days). An oestrogen antagonist, ICI 182,780, was used to determine whether or not the isoflavones activated Wnt signalling via oestrogen receptors (ERs). RESULTS: Genistein and daidzein suppressed adipogenic differentiation of AD-MSCs in a dose-dependent manner and inhibited expression of adipogenic markers, PPARγ, SREBP-1c and Glut 4, from mid-phase differentiation. Microarrays showed that anti-adipogenic effects of genistein were principally attributable to activation of Wnt signalling via ERs-dependent pathway, such as Erk/JNK signalling and LEF/TCF4 co-activators. These findings were supported by evidence that the effects of genistein were offset by ICI182,780. Unlike genistein, daidzein inhibited adipogenesis through stimulation of lipolysis, with for example, PKA-mediated hormone sensitive lipase. This is consistent with the increase in glycerol released from AD-MSCs. In conclusion, understanding that different sets of mechanisms of the two isoflavones on adipogenesis will help the design of novel strategies to prevent observed current epidemic levels of obesity, using isoflavones.

DNER modulates adipogenesis of human adipose tissue-derived mesenchymal stem cells via regulation of cell proliferation.

OBJECTIVES: In recent years, obesity has become a global epidemic, highlighting the necessity for basic research into mechanisms underlying growth of adipose tissue and differentiation of stem cells into adipocytes, in humans. For better understanding of cell signalling in adipogenesis, the role of DNER (delta/Notch-like EGF-related receptor) in adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSC) was investigated. MATERIALS AND METHODS: To assess the role of DNER in hAMSC adipogenesis, hAMSCs were transfected with DNER small interfering RNA (siDNER). Real-time quantitative reverse transcriptase polymerase chain reactions to assess expression levels of adipogenesis-related genes regulated by siDNER, cell cycle and immunoblot analyses were performed. RESULTS: First, it was determined that DNER mRNA was profoundly expressed in hAMSCs and reduced during adipogenic differentiation. Knockdown of DNER altered cell morphology, inhibited proliferation and increased frequency and efficiency of adipogenesis in hAMSC. Expression of CCAAT/enhancer-binding protein delta increased and proportion of cells in S phase decreased by knockdown of DNER, using specific siRNA. Moreover, adipocyte-specific genes including peroxisome proliferator-activated receptor gamma, fatty acid binding protein 4 and perilipin were up-regulated in siDNER compared to the siControl group during adipogenesis in hAMSC. CONCLUSIONS: These results indicate that DNER knockdown in hAMSC accelerated onset of adipogenic differentiation by bypassing mitotic clonal expansion during the early stages of adipogenesis.