Tumor necrosis factor-inducible gene 6 promotes liver regeneration in mice with acute liver injury

INTRODUCTION: Tumor necrosis factor-inducible gene 6 protein (TSG-6), one of the cytokines released by human mesenchymal stem/stromal cells (hMSC), has an anti-inflammatory effect and alleviates several pathological conditions; however, the hepatoprotective potential of TSG-6 remains unclear. We investigated whether TSG-6 promoted liver regeneration in acute liver failure. METHODS: The immortalized hMSC (B10) constitutively over-expressing TSG-6 or empty plasmid (NC: Negative Control) were established, and either TSG-6 or NC-conditioned medium (CM) was intraperitoneally injected into mice with acute liver damage caused by CCl(4). Mice were sacrificed at 3 days post-CM treatment. RESULTS: Higher expression and the immunosuppressive activity of TSG-6 were observed in CM from TSG-6-hMSC. The obvious histomorphological liver injury and increased level of liver enzymes were shown in CCl(4)-treated mice with or without NC-CM, whereas those observations were markedly ameliorated in TSG-6-CM-treated mice with CCl(4). Ki67-positive hepatocytic cells were accumulated in the liver of the CCl(4) + TSG-6 group. RNA analysis showed the decrease in both of inflammation markers, tnfα, il-1β, cxcl1 and cxcl2, and fibrotic markers, tgf-β1, α-sma and collagen α1, in the CCl(4) + TSG-6 group, compared to the CCl(4) or the CCl(4) + NC group. Protein analysis confirmed the lower expression of TGF-β1 and α-SMA in the CCl(4) + TSG-6 than the CCl(4) or the CCl(4) + NC group. Immunostaining for α-SMA also revealed the accumulation of the activated hepatic stellate cells in the livers of mice in the CCl(4) and CCl(4) + NC groups, but not in the livers of mice from the CCl(4) + TSG-6 group. The cultured LX2 cells, human hepatic stellate cell line, in TSG-6-CM showed the reduced expression of fibrotic markers, tgf-β1, vimentin and collagen α1, whereas the addition of the TSG-6 antibody neutralized the inhibitory effect of TSG-6 on the activation of LX2 cells. In addition, cytoplasmic lipid drops, the marker of inactivated hepatic stellate cell, were detected in TSG-6-CM-cultured LX2 cells, only. The suppressed TSG-6 activity by TSG-6 antibody attenuated the restoration process in livers of TSG-6-CM-treated mice with CCl(4). CONCLUSIONS: These results demonstrated that TSG-6 contributed to the liver regeneration by suppressing the activation of hepatic stellate cells in CCl(4)-treated mice, suggesting the therapeutic potential of TSG-6 for acute liver failure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-015-0019-z) contains supplementary material, which is available to authorized users

Obesity and risk of pancreatic cancer among postmenopausal women: the Women's Health Initiative (United States)

A total of 138 503 women in the Women's Health Initiative in the United States were followed (for an average of 7.7 years) through 12 September 2005 to examine obesity, especially central obesity in relation to pancreatic cancer (n=251). Women in the highest quintile of waist-to-hip ratio had 70% (95% confidence interval 10–160%) excess risk of pancreatic cancer compared with women in the lowest quintile

Intermittent fasting and continuous energy restriction result in similar changes in body composition and muscle strength when combined with a 12 week resistance training program

PURPOSE: The objective of this study was to compare the effects of 12 weeks of resistance training combined with either 5:2 intermittent fasting or continuous energy restriction on body composition, muscle size and quality, and upper and lower body strength. METHODS: Untrained individuals undertook 12 weeks of resistance training plus either continuous energy restriction [20% daily energy restriction (CERT)] or 5:2 intermittent fasting [~ 70% energy restriction 2 days/week, euenergetic consumption 5 days/week (IFT)], with both groups prescribed a mean of ≥ 1.4 g of protein per kilogram of body weight per day. Participants completed 2 supervised resistance and 1 unsupervised aerobic/resistance training combination session per week. Changes in lean body mass (LBM), thigh muscle size and quality, strength and dietary intake were assessed. RESULTS: Thirty-four participants completed the study (CERT = 17, IFT = 17). LBM was significantly increased (+ 3.7%, p < 0.001) and body weight (- 4.6%, p < 0.001) and fat (- 24.1%, p < 0.001) were significantly reduced with no significant difference between groups, though results differed by sex. Both groups showed improvements in thigh muscle size and quality, and reduced intramuscular and subcutaneous fat assessed by ultrasonography and peripheral quantitative computed tomography (pQCT), respectively. The CERT group demonstrated a significant increase in muscle surface area assessed by pQCT compared to the IFT group. Similar gains in upper and lower body strength and muscular endurance were observed between groups. CONCLUSION: When combined with resistance training and moderate protein intake, continuous energy restriction and 5:2 intermittent fasting resulted in similar improvements in body composition, muscle quality, and strength. ACTRN: ACTRN12620000920998, September 2020, retrospectively registered

A qualitative approach to designer as a product cue: proposed conceptual model of consumers perceptions and attitudes

‘Designer as a product cue’, which refers to the information presented about the product regarding the designer of that product, has increasingly been in use by marketers. However, there is a dire need to investigate its effects. Adopting a discovery-oriented grounded theory approach, this study proposes a conceptual model based on the insights gained through 14 semi-structured in-depth interviews about consumers’ evaluations of designer cues. Interview results are presented in four categories: product and consumption context-related issues (e.g. self-expressive potential of the product, product design distinctiveness, public vs private consumption), consumer related issues (e.g. need for uniqueness, perceived value), designer related issues (e.g. designer’s image, credibility) and firm related issues (e.g. company/brand image). Based on qualitative results, product and consumption related regulators as well as consumer and designer characteristics that regulate the processing routes through which designer cue influences consumer outcomes were integrated into a proposed conceptual model. These routes encompass emotional and cognitive paths to product-specific, self-related and company-related outcomes. Through the emotional route, a designer cue may be associated with more distinct states of consumers, such as privilege and sophistication and may lead to self-related outcomes, such as perceptions of social value and symbolic representation of consumer identity. Through the second route, a designer cue may also be associated with more cognition-based outcomes (e.g. product quality, attitude towards the product) as it unearths the intellectual and professional effort behind the product. This cognitive route may predominantly be related to product-specific (e.g. product quality) and company-related outcomes (e.g. company’s design-related image)