Multiple Roles of Sirtuin 6 in Adipose Tissue Inflammation

Adipose tissue (AT) inflammation is strongly associated with obesity-induced insulin resistance. When subjected to metabolic stress, adipocytes become inflamed and secrete a plethora of cytokines and chemokines, which recruit circulating immune cells to AT. Although sirtuin 6 (Sirt6) is known to control genomic stabilization, aging, and cellular metabolism, it is now understood to also play a pivotal role in the regulation of AT inflammation. Sirt6 protein levels are reduced in the AT of obese humans and animals and increased by weight loss. In this review, we summarize the potential mechanism of AT inflammation caused by impaired action of Sirt6 from the immune cells’ point of view. We first describe the properties and functions of immune cells in obese AT, with an emphasis on discrete macrophage subpopulations which are central to AT inflammation. We then highlight data that links Sirt6 to functional phenotypes of AT inflammation. Importantly, we discuss in detail the effects of Sirt6 deficiency in adipocytes, macrophages, and eosinophils on insulin resistance or AT browning. In our closing perspectives, we discuss emerging issues in this field that require further investigation

Expression analysis of diosgenin pathway genes and diosgenin accumulation in fenugreek sprouts after exposure to copper sulfate

Trigonella foenum-graecum L. is an annual herb belonging to the family Fabaceae commonly called Fenugreek. It is rich in various secondary metabolites such as alkaloids, flavonoids, phenolic compounds, and steroidal saponins. In recent years, diosgenin has much attention in the cosmetic, functional food, and pharmaceutical industries. In this study we aimed to examine the effect of different concentrations of copper sulfate (CuSO4) on growth, diosgenin biosynthetic (DB) gene expression, and diosgenin accumulation in T. foenum-graecum sprouts. Results showed that the seed germination, fresh weight, shoot length, and root length were gradually decreased with increasing the CuSO4 concentrations. In contrast, the expression level of DBGs i.e., TfSQS, TfSQLE, TfCAS, and TfSTRL were gradually upregulated with increasing the CuSO4 concentrations. Among all those tested concentrations, the expression levels of all those genes were significantly higher in 0.5 mM CuSO4 treated sprouts. The highest expression level was obtained in the TfCAS gene, which was 3.25-fold higher than the unexposed sprouts. The diosgenin content was significantly influenced in the CuSO4 exposed sprouts. The highest diosgenin content was achieved in the 5.0 mM followed by 1.0, 10.0, and 0.5 mM CuSO4 exposed concentrations, with a reduction of 41%, 39%, 36%, and 35%, respectively. From these results, it is shown that exposure of fenugreek sprout to CuSO4 is one of the suitable strategies to enhance the accumulation of diosgenin content

Biosynthesis of phenylpropanoids and their protective effect against heavy metals in nitrogen-fixing black locust (Robinia pseudoacacia)

Purpose: To examine the effect of various heavy metals (HMs) on phenylpropanoid pathway compounds in Robinia pseudoacacia.Methods: A series of pot culture experiments were performed to understand how the metabolic profile of phenylpropanoid compounds were affected by various HMs, such as redox-active HMs (AgNO3 and CuCl2), and non-redox-active HMs (HgCl2). Phenylpropanoid compound level was evaluated by high performance liquid chromatography.Results: The total phenylpropanoid level in leaves increased significantly in all the treated groups when compared to that in the untreated group (p < 0.05). However, a significant effect on the total phenylpropanoid levels was only found for redox-active HMs (p < 0.05), whereas non-redox-active HMs showed less accumulation. Chlorogenic acid and rutin were the two major phenylpropanoid compounds found after the plants were subjected to redox and non-redox-active HMs stress. However, when compared to these two compounds, the levels of catechin hydrate, epicatechin, p-coumaric acid, kaempferol, and quercetin were lower. Caffeic acid level was significantly decreased in both redox and non-redox-active HMs when compared to that in the control (p < 0.05). In addition, trans-cinnamic acid accumulation was altered based on the types and concentration of HMs.Conclusion: Phenylpropanoid metabolic pathway participated in the HM tolerance process for the protection of R. pseudoacacia from oxidative damage caused by HMs, thus allowing the species to grow in highly HMs-contaminated areas. Keywords: Heavy metals, Non-redox-active metals, Phenylpropanoid compounds, Redox-active metals, Robinia pseudoacaci

High glucose induces MCP-1 expression partly via tyrosine kinase–AP-1 pathway in peritoneal mesothelial cells

High glucose induces MCP-1 expression partly via tyrosine kinase–AP-1 pathway in peritoneal mesothelial cells.BackgroundHigh glucose in peritoneal dialysis solutions has been implicated in the pathogenesis of peritoneal fibrosis in chronic ambulatory peritoneal dialysis (CAPD) patients. However, the mechanisms are not very clear. Peritoneal macrophages seem to participate in the process of peritoneal fibrosis and monocyte chemoattractant protein-1 (MCP-1) plays a key role in the recruitment of monocytes toward the peritoneal cavity. However, little is known about the effect of high glucose on MCP-1 expression and its signal transduction pathway in human peritoneal mesothelial cells.MethodsMesothelial cells were cultured with glucose (5 to 100 mmol/L) or mannitol chronically for up to seven days. MCP-1 expression of mRNA and protein was measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA). Chemotactic activity of high-glucose–conditioned culture supernatant was measured by chemotactic assay. To examine the roles of the transcription factors activator protein-1 (AP-1) and nuclear factor-κB (NF-κB), electrophoretic mobility shift assay (EMSA) was performed.ResultsGlucose induced MCP-1 mRNA expression in a time- and dose-dependent manner. MCP-1 protein in cell culture supernant was also increased. Equivalent concentrations of mannitol had no significant effect. High-glucose–conditioned supernatant possessed an increased chemotactic activity for monocytes, which was neutralized by anti–MCP-1 antibody. EMSA revealed that glucose increased the AP-1 binding activity in a time- and dose-dependent manner, but not NF-κB. Curcumin, an inhibitor of AP-1, dose-dependently suppressed the induction of MCP-1 mRNA by high glucose. Tyrosine kinase inhibitors such as genistein (12.5 to 50 μmol/L) and herbimycin A (0.1 to 1 μmol/L) inhibited the high-glucose–induced MCP-1 mRNA expression in a dose-dependent manner, and also suppressed the high-glucose–induced AP-1 binding activity.ConclusionsHigh glucose induced mesothelial MCP-1 expression partly via the tyrosine kinase-AP-1 pathway

Incidental thyroid lesions detected by FDG-PET/CT: prevalence and risk of thyroid cancer

<p>Abstract</p> <p>Background</p> <p>Incidentally found thyroid lesions are frequently detected in patients undergoing FDG-PET/CT. The aim of this study was to investigate the prevalence of incidentally found thyroid lesions in patients undergoing FDG-PET/CT and determine the risk for thyroid cancer.</p> <p>Methods</p> <p>FDG-PET/CT was performed on 3,379 patients for evaluation of suspected or known cancer or cancer screening without any history of thyroid cancer between November 2003 and December 2005. Medical records related to the FDG-PET/CT findings including maximum SUV(SUV_max) and pattern of FDG uptake, US findings, FNA, histopathology received by operation were reviewed retrospectively.</p> <p>Results</p> <p>Two hundred eighty five patients (8.4%) were identified to have FDG uptake on FDG-PET/CT. 99 patients with focal or diffuse FDG uptake underwent further evaluation. The cancer risk of incidentally found thyroid lesions on FDG-PET/CT was 23.2% (22/99) and the cancer risks associated with focal and diffuse FDG uptake were 30.9% and 6.4%. There was a significant difference in the SUV_maxbetween the benign and malignant nodules (3.35 ± 1.69 vs. 6.64 ± 4.12; P < 0.001). There was a significant correlation between the SUV_maxand the size of the cancer.</p> <p>Conclusion</p> <p>The results of this study suggest that incidentally found thyroid lesions by FDG-PET/CT, especially a focal FDG uptake and a high SUV, have a high risk of thyroid malignancy. Further diagnostic work-up is needed in these cases.</p

Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

<p>Abstract</p> <p>Background</p> <p>Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer.</p> <p>Methods</p> <p>In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR), and human epithelial receptor-2 (HER2) were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC) according to ER, PR, and HER2 status.</p> <p>Results</p> <p>Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes.</p> <p>Conclusions</p> <p>Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.</p

Effect of heavy metals on phenylpropanoid biosynthesis in Euonymus alatus

The productivity of the phenylpropanoid biosynthesis pathway in plants varies depending on the type of stress. In this work, we looked into how different phenylpropanoid chemicals accumulated in Euonymus alatus following exposure to different concentrations of CuCl2 (0.1, 0.5, and 1 mM), HgCl2 (0.1, 0.5, and 1 mM), and NiSO4 (10, 50, and 100 mM). We analyzed some of the individual phenolic chemicals by high-performance liquid chromatography (HPLC). In nearly all cases, rutin showed the largest concentration among the phenylpropanoid chemicals, followed by epicatechin, sinapic acid, p-coumaric acid, trans-cinnamic acid, ferulic acid, and caffeic acid. However, due to the change in the concentration of the heavy metals, the amount of phenylpropanoid changed. The highest accumulation of phenylpropanoid was documented in 0.1 mM CuCl2, whereas it was reduced in 1 mM HgCl2 exposed plants. These findings unequivocally demonstrate that the phenylpropanoid metabolic pathway took part in the heavy metal tolerance process, which shielded E. alatus from the oxidative damage brought on by heavy metals. Thus, under a variety of environmental stress situations, this species with a high tolerance to heavy metals may survive