Background: To determine the effect of sumac on vasodilation and oxidative stress in vascular tissue. This study hypothesized that sumac would increase vasodilation and reduce vascular damage in vascular tissue taken from rats to improve symptoms and risk of vascular dementia.
Methods: Male Sprague-Dawley rats were fed a chow diet or a high fat diet (HFD) for ten weeks. Endothelium-dependent vasodilation was measured in isolated mesenteric arterioles that were treated with or without 80 µg/ml sumac in the superfusate throughout the experiment.
Results: Sumac did not improve vasodilation or in ex vivo arteries from rats fed a high fat diet. There were trends of improved vasodilation in sumac treated vessels from high fat diet rats, but sumac did not significantly improve vasodilation. In rats fed a chow diet, sumac prevented phenylephrine (PE) constriction in the vascular tissue. The most likely cause for this is the presence of Gallic acid in sumac. Another possible explanation is the presence of nitrates in sumac which may have prevented PE vasoconstriction.
Conclusions: Sumac did not significantly improve vasodilation in isolated arteries from rats fed a high fat diet. The results are inconclusive for the improvement of symptoms or risk of vascular dementia. In vivo treatment with sumac should be tested as results may differ.

A prominent aspect of Alzheimer’s disease (AD) is the presence of neuroinflammation is mediated by the activation of microglial cells, which are the immune cells in the central nervous system (CNS) that express an array of cytokines that may promote an inflammatory response. The main cytokines produced are: tumor necrosis factor-alpha (TNF-), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The presence of these cytokines in the CNS may lead to neuronal death, to the production of toxic chemicals (such as nitric oxide), and to the generation of amyloid beta (a major pathological feature of AD). Previous studies have shown that modulation of the inflammatory response in the nervous system can potentially prevent and/or delay the onset of neurodegenerative diseases such as AD. Therefore, it is important to identify the process that induces CNS inflammation. For example, mitochondrial lysates have been found to produce an inflammatory response due to their ability to stimulate TNF-, Aβ, and APP mRNA [10]. Interestingly, extracellular mitochondria have been detected in the brain due to neurons degrading old mitochondria extracellularly. Therefore, we set out to study the effect of whole mitochondria isolated by differential centrifugation from human neuroblastoma cells (BE(2)-M17 cells) on the neuroinflammatory response in a human microglia model (THP-1 cells). Despite our best efforts, in the end it was unclear whether the mitochondrial fraction or other cellular components induced the inflammatory response we observed. Thus, further work with an improved mitochondrial isolation method should be carried out to address this issue.

The natural habitat as well as the food abundance and food sources of avian species is changing due to urbanization, and such anthropocentric actions could lead to devastating impacts on bird populations. As changes in distribution and nutrition are thought to be related to the gut microbiome, the goal of this study was to determine the relationship between nutritional markers, including body mass, gizzard mass, triglycerides, free glycerol and glycogen, and the gut microbiome in urban and rural house sparrows (Passer domesticus), to understand physiological differences between urban and rural house sparrows. We hypothesized that increased access to human refuse, through urbanization, may significantly alter the gut microbiome and thus, the nutritional physiology-the effects of foods on metabolism-of urban birds. Fecal samples were collected from rural (n=13) and urban (n=7) birds to characterize the gut microbiome and plasma samples were collected to measure nutritional markers using commercially available kits. Following euthanasia, liver samples were collected to measure triglycerides, free glycerol and glycogen. While there were no significant differences in circulating triglycerides or free glycerol between populations, urban birds had significantly greater blood glucose (p=0.046) compared to rural birds, when normalized to body mass. Additionally, rural birds had significantly more plasma uric acid (p=0.016) and liver free glycerol (p=0.044). Higher blood glucose suggests greater accessibility to carbohydrates in an urban setting or higher rates of gluconeogenesis. Uric acid is a byproduct of purine catabolism and a potent antioxidant. Thus, higher uric acid suggests that rural birds may utilize more protein for energy. Finally, higher liver free glycerol in rural birds suggests they metabolize more fat but could also indicate that urban birds have greater glycerol gluconeogenesis, which may consume free glycerol resulting in higher glucose concentrations. However, the current study does not provide evidence for this as there were no significant differences in the gluconeogenic enzyme PEPCK-C levels between urban and rural house sparrows (p= 0.165). While triglyceride, glucose, and uric acid levels differed between urban and rural birds, there were additionally no significant differences in the gut microbiome, indicating that although nutritional physiology can be affected by distribution and varying food availability and sources, differences in the gut microbiome are evident at the phyla level.

CD4+CD25+ FOXP3+ cells are recognized as the most reliable regulatory T cell subset. However, the intracellular nature of the FOXP3 transcription factor limits its use for the isolation or selection of viable regulatory T cells for adoptive immunotherapy. Nuclear localization of FOXP3 has been more strongly associated with induced regulatory T cell (Treg) function than increased expression of FOXP3 alone. Several different cell culture methods and T cell activation techniques can induce increased expression of FOXP3 in a variety of T cell models, but Rapamycin (an mTOR inhibitor) was recently shown to differentially induce nuclear localization of FOXP3 when compared with IL-10 and TGFβ. Feline Tregs have been well characterized and share many of the phenotypic and functional characteristics of murine and human Tregs. We cultured feline Mya-1 T cells in conditions that would differentially promote effector or regulatory phenotypes and correlated nuclear localization of FOXP3 with other quantitative morphologic features using imaging flow cytometry. We compared the morphologic features of cells with high intra-nuclear concentrations of FOXP3 cultured without IL-2, with IL-2, and with IL-2 and Rapamycin before and after non-specific antigenic stimulation with Concanavalin-A. This analysis may help identify a population of pure regulatory T cells that would be more likely to maintain regulatory function following in-vitro expansion and activation. Furthermore, the feline T cell model could help elucidate important differences between murine and human Treg cells that would further translational efforts in adoptive immunotherapy. Now, we ask if nuclear localization of FOXP3 could be used to identify other morphologic differences between activated effector and regulatory T cells using a feline T cell line.

Humans have greatly altered the night-time photic environment via the production of artificial light at night (ALAN; e.g. street lights, car traffic, billboards, lit buildings). ALAN is problematic because it may significantly alter the seasonal/daily physiological rhythms or behaviors of animals. There has been considerable interest in the impacts of ALAN on health in humans and lab animals, but most such work has centered on adults and we know comparatively little about effects on young animals. We exposed 3-week-old king quail (Excalfactoria chinensis) to a constant overnight blue-light regime for 6 weeks and assessed weekly bactericidal activity of plasma against Escherichia coli - a commonly employed metric of innate immunity in animals. We found that chronic ALAN exposure significantly increased immune function, and that this elevation in immune performance manifested at different developmental time points in males and females. These results counter the pervasive notion that overnight light exposure is universally physiologically harmful to diurnal organisms and indicate that ALAN can provide sex-specific, short-term immunological boosts to developing animals.

Historically, studies of condition-dependent signals in animals have been male-centric, but recent work suggests that female ornaments can also communicate individual quality (e.g., disease state, fecundity). There has been a surge of interest in how urbanization alters signaling traits, but we know little about if and how cities affect signal expression in female animals. We measured carotenoid-based plumage coloration and coccidian (Isospora spp) parasite burden in desert and city populations of house finches to examine urban impacts on male and female health and attractiveness. In earlier work, we showed that male house finches are less colorful and more parasitized in the city, and we again detected that pattern in this study for males. However, though city females are also less colorful than their rural counterparts, we found that rural females were more parasitized. Also, regardless of sex and unlike rural birds, more colorful birds in the city were more heavily infected with coccidia. These results show that urban environments can disrupt signal honesty in female animals and highlight the need for more studies on how cities affect disease and condition-dependent traits in both male and female animals.

Weight cycling (WC) is characterized by repeated bouts of weight loss followed by regain. WC has been associated with a number of adverse health consequences and is a risk factor for cardiovascular disease. Body weight regulation is complex. Little is known about why women who intentionally lose weight are so likely to regain their weight back. Humans are motivated by a variety of psychological pressures as well as physiological stimuli that influence eating behaviors and weight control. One of the complex factors that has been shown to predict weight regain, in weight-reduced individuals, is hunger. Ghrelin is a known gastrointestinal hormone that rises during weight loss and is a strong trigger of hunger and increased appetite. Increased ghrelin levels have been associated with disordered eating behaviors and active weight loss. The Three Factor Eating Questionnaire (TFEQ-R18) describes elements that may affect hunger and satiety. These factors are: cognitive restraint (CR, defined as regulating food intake because of weight maintenance), uncontrolled eating (UE, defined as difficulty in regulating eating), and emotional eating (EE, refers to the tendency to eat more than needed because of mood state). Objective: The purpose of this study was to explore the associations of fasting plasma ghrelin with eating behaviors and weight cycling in overweight and obese women. Methods: This is a cross-sectional observation of women aged 20-60 years who completed a Weight and Lifestyle Inventory (WALI) and the TFEQ-R18. Women provided a 12-h fasting blood sample and plasma ghrelin was measured using a commercial radioimmunoassay (ELISA kit Cat# EZGRA-88k). Intra- and inter-assay CVs were 88.4% + 13.8% and 84.4% + 8.4% respectively. Descriptive data were computed and Pearson correlations were assessed adjusting for age and body weight (SPSS, v23). Results: A WC Index (WCI) was computed as number of WC reported x the amount of weight lost per cycle. 61 women (mean age: 39.3 + 11 yr; BMI: 31.4 + 7; WCI: 70 + 60; range = 0 to 253) completed questionnaires. Ghrelin was significantly and negatively correlated to weight (R= -0.25, P = 0.03), BMI (R= -0.32, P = .006), UE (R = -0.29, p = 0.02), and EE (R = -0.29, p = 0.04). Ghrelin was not significantly related to WCI. WCI was not significantly correlated with any TFEQ-18 subscales. Conclusion: In this observational study, lower ghrelin was associated with higher UE and EE. Thus physiological hunger sensations from ghrelin secretion, is not a likely stimulus of eating behavior in these women. There are a host of psychological triggers, such as stress, loneliness, guilt, anger etc. that may enhance eating. Future research will need to explore what psychological triggers influence eating behavior and why obese women are resistant to the powerful physiological hunger cues of ghrelin.

The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.

It is presently believed that brown adipose tissue (BAT) is an important tissue in the control of obesity because it has the propensity to increase energy expenditure. The purpose of this study was to attempt to quantify the thermogenesis of BAT when four rats were exposed to a progression of low-fat to high-fat diet. Exogenous norepinephrine (NE) injections (dose of 0.25 mg/kg i.p.) were administered in order to elicit a temperature response, where increases in temperature indicate increased activity. Temperatures were measured via temperature sensing transponders that had been inserted at the following three sites: interscapular BAT (iBAT), the abdomen (core), and lower back (reference). Data showed increased BAT activity during acute (2-3 weeks) high fat diet (HFD) in comparison to low fat diet (LFD), but a moderate to marked decrease in BAT activity during chronic HFD (6-8 weeks) when compared to acute HFD. This suggests that while a HFD may initially stimulate BAT in the short-term, a long-term HFD diet may have negative effects on BAT activation.

Doxorubicin (DOX) is a cardiotoxic, anthracycline-based, anti-neoplastic agent that causes pathological cardiac remodeling due to altered protein expression associated with cardiotoxicity. DOX cardiotoxicity causes increased Akt phosphorylation, blunted AMPK phosphorylation and upregulated mTOR phosphorylation. Akt is activated by cellular stress and damage. AMPK is activated by increases in AMP and ADP concentrations and decreased ATP concentration. mTOR is active in cellular growth and remodeling. These proteins are cellular kinases with cascades that are influenced by one another. Exercise preconditioning may diminish the cardiotoxic effects on these proteins. Female, Ovariectomized Sprague-Dawley rats (N=33) were randomized to: Exercise+DOX (EX+DOX, n=9); Exercise+Vehicle (EX+VEH, n=8); Sedentary+DOX (SED+DOX, n=8); and Sedentary+Vehicle (SED+VEH, n=8) groups. DOX (4mg/kg) or VEH (saline) intraperitoneal injections were administered bi-weekly (cumulative dose of 12mg/kg). VEH animals received body weight matched volumes of saline based on dosing in animals receiving DOX. Exercise (EX) animals underwent high intensity (85-95% VO2 peak) interval training (HIIT) (4x4 min bouts) separated by low intensity (50-60% VO2max) intervals (2 min bouts) 5 days per week. Exercise began 1 week prior to the first injection and was continued throughout the study. Rats were euthanized 5 days after the last injection. Left ventricular tissue was isolated, processed into lysate and used for western blot analyses [2x2 ANOVA; (α=0.05)]. DOX induced significant phosphorylation of Akt and mTOR (p=0.035; p=0.032) only in SED+DOX rats, but unchanged in EX+DOX rats. No significant differences (p=0.374) in AMPK phosphorylation were observed between groups. Exercise Preconditioning prevents some DOX-induced changes in the cardiac mTOR signaling pathway implicated in pathological remodeling.