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Background: The studies on cancer-stem-cells (CSCs) have attracted so much attention in recent years as possible therapeutic implications. This study was carried out to investigate the gene expression profile of CSCs in human lung adenocarcinoma A549 cells.

This longitudinal study employed the Infant Behavior Questionnaire-Revised in assessing temperamental differences between infants at 6 months (n = 114 US, 184 Dutch) and 12 months (n = 92 US, 172 Dutch) from the United States of America and The Netherlands. Main effects indicated that Dutch infants were rated higher on the Orienting/Regulatory Capacity factor and fine-grained dimensions of Smiling and Laughter, Falling Reactivity, Cuddliness, Low-Intensity Pleasure, and Soothability; whereas US infants received higher ratings on the Negative Affectivity factor and on dimensions of Activity Level, Vocal Reactivity, Fear, Frustration, and Sadness. Cultural differences for Orienting/Regulatory Capacity were more pronounced in early infancy, cultural differences for Fear were stronger in late infancy, and US infants demonstrated higher Duration of Orienting at 12 months only. Culture also appeared to impact the pace of consolidation of temperamental characteristics, with greater stability exhibited by US than Dutch infants in Smiling and Laughter and Vocal Reactivity.

It has previously been demonstrated that hypoxia has diverse stimulatory effects on adipose‑derived stem cells (ASCs), however, metabolic responses under hypoxia remain to be elucidated. Thus, the present study aimed to investigate the glucose uptake and metabolism of ASCs under hypoxic conditions, and to identify the underlying molecular mechanisms. ASCs were cultured in 1% oxygen, and experiments were conducted in vitro. As determined by proteomic analysis and western blotting, GAPDH and enolase 1 (ENO1) expression were upregulated under hypoxia. In addition, lactate production was significantly increased, and mRNA levels of glycolytic enzymes, including GAPDH, ENO1, hexokinase 2 (HK2), and lactate dehydrogenase α (LDHα) were upregulated. Hypoxia‑inducible factor 1‑α (HIF‑1α) expression was increased as demonstrated by western blotting, and a pharmacological inhibitor of HIF‑1α significantly attenuated hypoxia‑induced lactate production and expression of glycolytic enzymes. It was also observed that hypoxia significantly increased glucose uptake in ASCs, and glucose transporter (GLUT)1 and GLUT3 expression were upregulated under hypoxia. Pharmacological inhibition of the HIF‑1α signaling pathways also attenuated hypoxia‑induced GLUT1 and GLUT3 expression. These results collectively indicate that hypoxia increases glucose uptake via GLUT1 and GLUT3 upregulation, and induces lactate production of ASCs via GAPDH, ENO1, HK2, and LDHα. Furthermore, HIF‑1α is involved in glucose uptake and metabolism of ASCs.

Loss of BMP (bone morphogenic protein) signaling induces a phenotype switch of pulmonary arterial smooth muscle cells (PASMCs), which is the pathological basis of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Here, we identified FGF12 (fibroblast growth factor 12) as a novel regulator of the BMP-induced phenotype change in PASMCs and elucidated its role in pulmonary vascular remodeling during PAH development. Using murine models of PAH and lung specimens of patients with PAH, we observed that FGF12 expression was significantly reduced in PASMCs. In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. Mechanistically, FGF12 regulated the BMP-induced phenotype change by inducing MEF2a (myocyte enhancer factor 2a) phosphorylation via p38MAPK signaling, thereby modulating the expression of MEF2a target genes involved in cell proliferation and differentiation. Furthermore, we observed that TG (transgenic) mice with smooth muscle cell–specific FGF12 overexpression were protected from chronic hypoxia–induced PAH development, pulmonary vascular remodeling, and right ventricular hypertrophy. Consistent with the in vitro data using human PASMCs, FGF12 TG mice showed increased MEF2a phosphorylation and a substantial change in MEF2a target gene expression, compared with the WT (wild type) controls. Overall, our findings demonstrate a novel BMP/FGF12/MEF2a pathway regulating the PASMC phenotype switch and suggest FGF12 as a potential target for the development of therapeutics for ameliorating pulmonary vascular remodeling in PAH.

BackgroundMetabolic syndrome (MetS) is associated with increased risks of diabetes and coronary artery disease (CAD). Despite the controversial inclusion of established diabetes in MetS, the association between MetS and CAD according to diabetes status has not been elucidated in the Asian population.MethodsWe evaluated the association between MetS and CAD using the parameters including any plaque, obstructive plaque, and coronary artery calcium score (CACS) >100 according to diabetes status in 2,869 symptomatic Korean subjects who underwent cardiac computed tomographic angiography.ResultsThe prevalence of MetS was significantly higher in the diabetic subjects than in the non-diabetic subjects (69% vs. 34%, P <0.001). The incidence of any plaque (64% vs. 43%, P <0.001), obstructive plaque (26% vs. 13%, P = 0.006), and CACS >100 (23% vs. 12%, P = 0.012) was significantly higher in diabetic subjects than in non-diabetic subjects. Among the MetS components, decreased high-density lipoprotein level was significantly associated with any plaque (odds ratio [OR] 1.35), obstructive plaque (OR 1.55), and CACS >100 (OR 1.57) in the non-diabetic subjects (P <0.01, respectively). However, none of the MetS components were associated with all the parameters in the diabetic subjects. Multivariate regression analysis revealed that MetS and the number of MetS components (MetSN) were independently associated with any plaque (MetS: OR 1.55, P <0.001; MetSN: OR 1.22, P <0.001), obstructive plaque (MetS: OR 1.52, P = 0.003; MetSN: OR 1.25, P <0.001), and CACS >100 (MetS: OR 1.46, P = 0.015; MetSN: OR 1.21, P = 0.004) only in the non-diabetic subjects, respectively.ConclusionsMetS was independently associated with the presence and severity of CAD only in the non-diabetic subjects among the symptomatic Korean population.

Background Systemic inflammatory response syndrome (SIRS) is common in severe fulminant hepatic failure (FHF) and has a high mortality rate (20–50%) due to irreversible cerebral edema or sepsis. Stem cell-based treatment has emerged as a promising alternative therapeutic strategy to prolong the survival of patients suffering from FHF via the inhibition of SIRS due to their immunomodulatory effects. Methods 3D spheroids of adipose-derived mesenchymal stem cells (3D-ADSC) were prepared by the hanging drop method. The efficacy of the 3D-ADSC to rescue FHF was evaluated in a d-galactosamine/lipopolysaccharide (GalN/LPS)-induced mouse model of FHF via intraportal transplantation of the spheroids. Results Intraportally delivered 3D-ADSC better engrafted and localized into the damaged livers compared to 2D-cultured adipose-derived mesenchymal stem cells (2D-ADSC). Transplantation of 3D-ADSC rescued 50% of mice from FHF-induced lethality, whereas only 20% of mice survived when 2D-ADSC were transplanted. The improved transplantation outcomes correlated with the enhanced immunomodulatory effect of 3D-ADSC in the liver microenvironment. Conclusion The study shows that the transplantation of optimized 3D-ADSC can efficiently ameliorate GalN/LPS-induced FHF due to improved viability, resistance to exogenous ROS, and enhanced immunomodulatory effects of 3D-ADSC.