Functional Polymorphism of IL-1 Alpha and Its Potential Role in Obesity in Humans and Mice

Proinflammatory cytokines secreted from adipose tissue contribute to the morbidity associated with obesity. IL-1α is one of the proinflammatory cytokines; however, it has not been clarified whether IL-1α may also cause obesity. In this study, we investigated whether polymorphisms in IL-1α contribute to human obesity. A total of 260 obese subjects were genotyped for IL-1α C-889T (rs1800587) and IL-1α G+4845T (rs17561). Analyses of genotype distributions revealed that both IL-1α polymorphisms C-889T (rs1800587) and G+4845T (rs17561) were associated with an increase in body mass index in obese healthy women. In addition, the effect of rs1800587 on the transcriptional activity of IL-1α was explored in pre-adipocyte 3T3-L1 cells. Significant difference was found between the rs1800587 polymorphism in the regulatory region of the IL-1α gene and transcriptional activity. We extended these observations in vivo to a high-fat diet-induced obese mouse model and in vitro to pre-adipocyte 3T3-L1 cells. IL-1α levels were dramatically augmented in obese mice, and triglyceride was increased 12 hours after IL-1α injection. Taken together, IL-1α treatment regulated the differentiation of preadipocytes. IL-1α C-889T (rs1800587) is a functional polymorphism of IL-1α associated with obesity. IL-1α may have a critical function in the development of obesity

SoSoSo or its active ingredient chrysophanol regulates production of inflammatory cytokines & adipokine in both macrophages & adipocytes

Background & objectives: Obesity is now considered as a major risk factor for the development of fatty liver diseases, cardiovascular diseases, and atherosclerosis. SoSoSo is a newly developed dietary supplement made of seven medicinal herbs. This study was aimed at examining the anti-obesity effect of SoSoSo or its active ingredient chrysophanol on the production of inflammatory cytokines and adipokine in macrophyage cell line RAW264 and 3T3-L1 adipocytes. Methods: No release was measured as a form of nitrite by Griess method. The production of inflammatory cytokines and adipokine were measured with the ELISA method. The m-RNA expression of each cytokine and adipokine were measured using RT-PCR. The nuclear proteins for NF-κB were analyzed with western blotting. Results: SoSoSo or chrysophanol significantly inhibited the nitric oxide production in lipopolysaccharide-stimulated RAW264 cells as well as in RAW264 cells-conditioned medium (CM)-treated 3T3-L1 cells. The production of interleukin (IL)-6 and tumour necrosis factor (TNF)-α were inhibited by SoSoSo or chrysophanol. In addition, SoSoSo or chrysophanol inhibited the activation of nuclear factor-κB in RAW264 cells. SoSoSo or chrysophanol inhibited the productions of IL-6, TNF-α, and monocyte chemoattractant protein-1 as well as the reduction of adiponectin production in CM-treated 3T3-L1 cells. Interpretation & conclusions: These results suggest a potential of SoSoSo or chrysophanol as a source of anti-inflammatory agent for obesity. Further in vivo studies would be required to confirm these findings

Synthesis of carbon nanotube fibers from carbon precursors with low decomposition temperatures using a direct spinning process

Carbon nanotube (CNT) fibers were synthesized from ethylene, acetylene, or methane by separately injecting ferrocene and the carbon precursors during a direct spinning process. Ethylene and acetylene have low decomposition temperatures. It was difficult to synthesize CNT fibers from these precursors using the direct spinning method. CNT fibers were continuously synthesized by delaying the contact time between the catalyst particles and the carbon precursors, which provided sufficient time for catalyst growth. Changes in catalyst size from 2 nm to 20 nm were observed as a function of the catalyst formation step setting temperature (350-440 degrees C) and the carbon precursor injection tube length (8-310 mm), and the relationship between the catalyst size and the CNT diameter was characterized. The CNT fibers had higher I-G/I-D ratios when synthesized from acetylene (69.87) or ethylene (18.52) than from methane (3.61). The choice of the carbon precursor had a much larger effect on the I-G/I-D ratio of the synthesized CNT fibers than the other operating variables. (C) 2017 Elsevier Ltd. All rights reserved.112sciescopu

Noncanonical functions of glucocorticoids: A novel role for glucocorticoids in performing multiple beneficial functions in endometrial stem cells

Abstract Chronic stress has a negative impact on many fertility-related functions; thus, the recent decline in female fertility seems to be at least partially associated with increased stress. The secretion of glucocorticoids is a typical endocrine response to chronic stress and indirectly reduces uterine receptivity through the hypothalamus-pituitary-gonadal (HPG) axis. However, in addition to its well-known canonical role, the direct effects of chronic stress-induced glucocorticoids on various uterine functions and their underlying molecular mechanisms are complex and have not yet been revealed. Recent studies have found that resident stem cell deficiency is responsible for the limited regenerative potential of the endometrium (the innermost lining of the uterine cavity) during each menstrual cycle, which subsequently increases infertility rates. In this context, we hypothesized that stress-induced glucocorticoids directly damage endometrial stem cells and consequently negatively affect endometrial reconstruction, which is important for uterine receptivity. In addition to its well-known canonical roles, we identified for the first time that cortisol, the most abundant and potent glucocorticoid in humans, directly suppresses the multiple beneficial functions (self-renewal, transdifferentiation, and migratory potential) of human endometrial stem cells through its functional receptor, glucocorticoid receptor (GR). Glucocorticoids inhibit well-known survival signals, such as the PI3K/Akt and FAK/ERK1/2 pathways. More importantly, we also found that immobilization of stress-induced glucocorticoids suppresses the various beneficial functions of tissue resident stem cells in vivo. To the best of our knowledge, this is the first study to investigate the direct effects of glucocorticoids on the regenerative capacity of endometrial stem cells, and the findings will facilitate the development of more promising therapeutic approaches to increase female fertility

T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose Uptake

It has been reported that [3-(1,1'-biphenyl-4-yl)-2-(1-methyl-5-dimethylamino-pentylamino)-3,4-dihydroquinazolin-4-yl]-N-benzylacetamide 2hydrochloride (KYS05090), a selective T-type Ca2+ channel blocker, reduces tumor volume and weight in the A549 xenograft model, but the molecular mechanism of cell death has not yet been elucidated. In this study, KYS05090 induced autophagy- and apoptosis-mediated cell death in human lung adenocarcinoma A549 cells. Although KYS05090 decreased intracellular Ca2+ levels, it was not directly related with KYS05090-induced cell death. In addition, KYS05090 generated intracellular reactive oxygen species (ROS) and reduced glucose uptake, and catalase and methyl pyruvate prevented KYS05090-induced cell death. These results indicate that KYS05090 can lead to autophagy and apoptosis in A549 cells through ROS generation by inhibiting glucose uptake. Our findings suggest that KYS05090 has potential chemotherapeutic value for the treatment of lung cancer