Green tea extract supplementation ameliorates CCl4-induced hepatic oxidative stress, fibrosis, and acute-phase protein expression in rat

Background/PurposeWe evaluated the long-term effects of green tea extract (GTE) supplementation on oxidative stress, biliary acute phase protein expression, and liver function in CCl4-induced chronic liver injury.MethodsWe evaluated the antioxidant activity of GTE in comparison with those of vitamin C, vitamin E, and β-carotene in vitro by using an ultrasensitive chemiluminescence analyzer. Chronic liver injury was induced by intraperitoneally administering carbon tetrachloride (CCl4) (1mL/kg body weight, twice weekly) to female Wistar rats for 8 weeks. The effects of low (4mg/kg body weight per day) and high (20mg/kg body weight per day) doses of intragastric GTE on CCl4-induced liver dysfunction and fibrosis were examined by measuring the bile and blood reactive oxygen species levels and biochemical parameters by using Western blot and two-dimensional polyacrylamide gel electrophoresis techniques.ResultsGTE has greater scavenging activity against O2–, H2O2, and Hypochlorous acid (HOCl) in vitro than vitamin C, vitamin E, and β-carotene do. In vivo, CCl4 markedly increased bile and blood reactive oxygen species production, lipid accumulation, number of infiltrated leukocytes, fibrosis, hepatic hydroxyproline content, and plasma alanine aminotransferase and aspartate aminotransferase activities, and reduced plasma albumin levels. Two-dimensional polyacrylamide gel electrophoresis revealed that CCl4 increased the acute-phase expression of six biliary proteins and decreased hepatic B-cell lymphoma 2 (Bcl-2), catalase, and CuZn superoxide dismutase protein expression. GTE supplementation attenuated CCl4-enhanced oxidative stress, levels of biochemical parameters, pathology, and acute-phase protein secretion, and preserved antioxidant/antiapoptotic protein expression.ConclusionGTE supplementation attenuates CCl4-induced hepatic oxidative stress, fibrosis, acute phase protein excretion, and hepatic dysfunction via the antioxidant and antiapoptotic defense mechanisms

Craniometrics reveal "two layers" of prehistoric human dispersal in eastern Eurasia

This cranio-morphometric study emphasizes a "two-layer model" for eastern Eurasian anatomically modern human (AMH) populations, based on large datasets of 89 population samples including findings directly from ancient archaeological contexts. Results suggest that an initial "first layer" of AMH had related closely to ancestral Andaman, Australian, Papuan, and Jomon groups who likely entered this region via the Southeast Asian landmass, prior to 65–50 kya. A later "second layer" shared strong cranial affinities with Siberians, implying a Northeast Asian source, evidenced by 9 kya in central China and then followed by expansions of descendant groups into Southeast Asia after 4 kya. These two populations shared limited initial exchange, and the second layer grew at a faster rate and in greater numbers, linked with contexts of farming that may have supported increased population densities. Clear dichotomization between the two layers implies a temporally deep divergence of distinct migration routes for AMH through both southern and northern Eurasia

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Green tea extract supplementation ameliorates CCl4-induced hepatic oxidative stress, fibrosis, and acute-phase protein expression in rat

Background/Purpose: We evaluated the long-term effects of green tea extract (GTE) supplementation on oxidative stress, biliary acute phase protein expression, and liver function in CCl4-induced chronic liver injury. Methods: We evaluated the antioxidant activity of GTE in comparison with those of vitamin C, vitamin E, and beta-carotene in vitro by using an ultrasensitive chemiluminescence analyzer. Chronic liver injury was induced by intraperitoneally administering carbon tetrachloride (CCl4) (1 mL/kg body weight, twice weekly) to female Wistar rats for 8 weeks. The effects of low (4 mg/kg body weight per day) and high (20 mg/kg body weight per day) doses of intragastric GTE on CCl4-induced liver dysfunction and fibrosis were examined by measuring the bile and blood reactive oxygen species levels and biochemical parameters by using Western blot and two-dimensional polyacrylamide gel electrophoresis techniques. Results: GTE has greater scavenging activity against O-2(-), H2O2, and Hypochlorous acid (HOCl) in vitro than vitamin C, vitamin E, and beta-carotene do. In vivo, CCl4 markedly increased bile and blood reactive oxygen species production, lipid accumulation, number of infiltrated leukocytes, fibrosis, hepatic hydroxyproline content, and plasma alanine aminotransferase and aspartate aminotransferase activities, and reduced plasma albumin levels. Two-dimensional polyacrylamide gel electrophoresis revealed that CCl4 increased the acute-phase expression of six biliary proteins and decreased hepatic B-cell lymphoma 2 (Bcl-2), catalase, and CuZn superoxide dismutase protein expression. GTE supplementation attenuated CCl4-enhanced oxidative stress, levels of biochemical parameters, pathology, and acute-phase protein secretion, and preserved antioxidant/antiapoptotic protein expression. Conclusion: GTE supplementation attenuates CCl4-induced hepatic oxidative stress, fibrosis, acute phase protein excretion, and hepatic dysfunction via the antioxidant and antiapoptotic defense mechanisms. Copyright (C) 2012, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved

Evaluation of Shoulder Microcirculation Abnormality Using Laser Doppler Flowmetry

Severe neck-shoulder pain induces functional limitations in both life and work. The purpose of this study was to determine the characteristics of shoulder microcirculation abnormality in workers. This study recruited 32 workers and patients, both n = 16. Questionnaires were administered, and Laser Doppler Flowmetry (LDF) was used to measure microcirculatory blood flow (MBF) at the myofascial trigger points (MTrPs) on the shoulders. The absolute-deviationMMBF represented the mean MBF (MMBF) variability among subjects. The differences in the life characteristics, shoulder pain level, and microcirculatory characteristics at MTrPs between the two groups were compared. It was found that shoulder pain level was significantly higher in the patient than in the control group (p &lt; 0.001). Deviation of the MMBF value beyond the postulated &ldquo;normal range&rdquo; of 60&ndash;80 was significantly higher in the patient than in the control group (p &lt; 0.001). The MMBF deviation was significantly correlated with shoulder pain level, pain duration, and the symptom effect (p &lt; 0.01, n = 32). A normal range for the MMBF of 60&ndash;80 on the shoulder near MTrPs is hypothesized for the first time based on this study. Noninvasive LDF can be used to assess abnormality in the MBF on shoulder MTrPs at an early stage

Media 2: Optical zoom camera module using two poly-dimethylsiloxane deformable mirrors

Originally published in Applied Optics on 10 October 2014 (ao-53-29-H248