Browsing by Author "Park, Yoonjung"
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Item Effects of Physical Activity Status and Exercise Modality on the T-Cell and Monocyte Response to Acute Exercise in Older Adults(2020-05) Levine, Rachel Graff; Markofski, Melissa M.; LaVoy, Emily C.; Park, Yoonjung; Jennings, KristoferOlder adults are at increased risk for many inflammation-associated chronic diseases, especially when aging is combined with physical inactivity. Maintaining an active lifestyle significantly reduces the risk of chronic disease in older adulthood, which may be due, in part, to the ability of regular exercise to maintain optimal immune function and minimize chronic inflammation. The specific immune system and inflammatory effects of cardiorespiratory (CRE) compared to resistance (RE) exercise in older adults are not fully understood. The purpose of this study was to examine the effects of exercise modality (cardiorespiratory vs. resistance training), and training status (physically active vs. inactive) on the immune system and inflammatory response to acute exercise of physically active older adults (OPA) and physically inactive older adults (OPI). Twenty-four healthy older adults (OPA n=12; OPI n=12) completed one bout of CRE and one bout of RE in a randomized order, both at a moderate intensity, and separated by at least 7 days. Blood samples were collected pre-exercise, post-exercise, and 1h post-exercise (recovery) time points and analyzed for CD4+ and CD8+ T-cells and T-cell subsets expressing surface markers CD45RA, CD62L, CD57, CD161, and CD196, and monocytes and monocyte subsets expressing surface markers CD11b, CCR5, CX3CR1, and CCR2. Monocyte function was assessed in vitro by LPS-stimulated cytokine (IL-6 and TNF) secretion and a glucocorticoid resistance assay. OPI had higher numbers of circulating CD57+ EMRA CD4+ T-cells (mean ± SE; OPA, 1 ± 2 cells/μL; OPI, 6 ± 2 cells/μL) and higher CCR2+ non-classical monocytes MFI (mean ± SE arbitrary units; OPA, 8 ± 4; OPI, 21 ± 4) than OPA at rest. Furthermore, RE mobilized more T-cell and monocyte subsets than CRE in both OPA and OPI groups, and CRE resulted in increased LPS-stimulated TNF production and decreased Th17 cell mobilization post-exercise, while RE caused decreased LPS-stimulated TNF production post-exercise and increased Th17 cell mobilization. Taken together, there were not major differences between the OPA and OPI response to acute exercise. However, differences in the immune system and inflammatory response to CRE compared to RE may exist and these differences may provide important insight to informing future exercise prescriptions for older adults to minimize inflammation and promote optimal immune function.Item Prevalence of Metabolic Syndrome Based on Activity Type and Dietary Habits in Extremely Low-Income Individuals(2024-05-29) Su, Kunxia; Kim, Yonghwan; Park, YoonjungA high prevalence of metabolic syndrome (MS) and cardiovascular disease among low-income individuals has often been reported. However, there is still a lack of research on the relationship between basic livelihood security (BLS) and MS. This study investigated the prevalence of MS according to activity type, dietary habits, and the nutrient intake characteristics of individuals receiving BLS. Data from 14,803 men and 20,299 women were analyzed to assess the association between receiving BLS and MS. The associations between MS and various factors were analyzed separately in men and women by logistic regression analysis. In this cohort, 5.9% of men and 6.8% of women received BLS; of these, 46.9% and 47.7% had MS, respectively. High caloric intake, low-frequency breakfast consumption, and no nutritional education were associated with MS in both men and women. Among those with a low-frequency walking habit and strength training activity type, MS increased by 1.58 and 1.57 times in men and by 1.47 and 2.16 times in women, respectively. Men who were sedentary for 8 h or more had an increased risk of MS, but there was no association between these in women. BLS nutritional intake characteristics were high in carbohydrates and fat and low in dietary fiber and vitamin C (p < 0.05). In conclusion, establishing a healthy eating pattern through nutritional education and increasing walking and strength training may reduce the risk of MS.Item Redox Physiology of Elite Endurance Athletes(2022-08) Azadan, Rod Jason; Ledoux, Tracey A.; Simpson, Richard J.; Pedlar, Charles R.; O'Connor, Daniel P.; Park, YoonjungAs participation in sports and physical activity continues to thrive around the globe and athletes continue to push their limits to compete at the highest level, sport related injury and illness have become a concern. It is well known that illness and injury increase with athlete training load, however, so does performance. That leaves athletes and their support team constantly trying to find the edge of their physical and physiological training tolerance - especially elite and professional athletes. Despite great advances in science and technology, training load is still primarily managed via trial and error and subjective athlete feedback measures such as self-perception of mood, fatigue, soreness, and exertion. Because biomarkers of redox balance in the peripheral blood supply have shown early promise as a quantitative measure to assess the physiological response to training and competition, we sought to determine the effects of semi-acute physiological stressors on point-of-care (PoC) biomarkers of redox balance in a sample of elite endurance track athletes and compare those values to reported clinical values. The aims of this dissertation were divided into four hypotheses. First, despite extensive training, PoC redox biomarkers will reveal significantly lower oxidative stress in elite endurance track athletes relative to published values associated with clinical (disease) states. Second, because relative training load is typically the highest during pre-season training of endurance track athletes, (general preparation periodization phase), PoC redox biomarkers will show significantly higher oxidative stress during pre-season training relative to other training phases throughout the year. Third, periods of altitude training will be associated with significantly higher oxidative stress than sea level training. And finally, mRNA COVID-19 vaccination (SPIKEVAX™ (mRNA-1273), Moderna Co., Cambridge, MA, USA) will be associated with a significant but transient increase of oxidative stress and inflammation [i.e, high sensitivity C-Reactive Protein (hsCRP)]. To test the first hypothesis, PoC redox biomarker values collected from 24 elite endurance track athletes over a 5-year period were analyzed by athlete and compared to published data on independent samples involving clinical conditions. To test the second hypothesis, the PoC redox biomarker values collected from 24 elite endurance track athletes over a 5-year period were analyzed by month over the course of the competitive year to evaluate alterations in redox balance relative to time-in-season. To test the third hypothesis, PoC redox samples collected for eight elite endurance track athletes throughout the course of an altitude training camp were analyzed for alterations after 5, 12, 19 and 26 days at altitude relative to athlete specific sea-level baseline values. To test the fourth hypothesis, PoC redox biomarkers as well as hsCRP samples collected for nine elite endurance track athletes prior to and throughout the course of mRNA vaccination were analyzed for alterations in redox balance. In support of our first hypothesis, it was found that mean oxidative stress levels in elite endurance track athletes were lower than reported values for clinical states, but not significantly different than healthy controls or most other characterized athletic populations. Additionally, when alterations in athlete redox balance exceeded clinically relevant levels, the response was predominantly dynamic, quickly returning to within normal ranges. In support of our second hypothesis, it was observed that oxidative stress (i.e., OSI) was elevated during pre-season training of elite endurance track athletes, particularly in December (i.e., General Preparatory training period). This alteration in redox balance was primarily driven by a decrease in anti-oxidative capacity (i.e., FORD). Contrary to our third hypothesis, no significant alteration in redox balance was detected over 26 days of training at altitude in our sample of athletes. And in support of our final hypothesis, it was observed that COVID-19 mRNA vaccination transiently increased oxidative stress (i.e., OSI) 6 days after the first vaccine dose, with a reduction in anti-oxidative capacity (i.e., FORD) that persisted throughout the inter-dose period. Additionally, a stark but transient rise in hsCRP was detected in the first 6 days after the first COVID-19 mRNA vaccine dose in some by not all athletes. From these results, we conclude that PoC redox biomarkers are a valuable objective means to monitor the physiological condition and resilience of athletes, especially for high level programs where professional longevity depends on continued health, minute fluxuations in athlete performance are meaningful, and sport scientists are available to interpret the data from this pioneering bio-analytical method.Item Role of Physical Activity in Inflammasome-mediated Vascular Endothelial Dysfunction in Obesity(2019-12) Lee, Jonghae; Park, Yoonjung; Umetani, Michihisa; LaVoy, Emily C.; O'Connor, Daniel P.Obesity contributes to the development of cardiovascular disease (CVD) which is a leading cause of mortality in the world. Endothelial dysfunction, the earliest event of CVD, is largely attributed to a complex interplay of nitric oxide (NO) production, oxidative stress, and inflammation. The proinflammatory cytokine interleukin-1β (IL-1β) is processed by nucleotide-binding oligomerization-domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome-mediated caspase-1 cleavage and is a crucial mechanism for vascular pathology in obesity. Physical activity is the first line of defense against obesity-associated vascular health problems since it has multiple protective properties operating through a myriad of physiological mechanisms. However, no study has reported whether physical activity affects NLRP3 inflammasome-associated vascular dysfunction in obesity, nor have any studies, to date, fully determined the underlying mechanisms responsible for the vascular health improvements in response to exercise. Also, considering that abnormal dilatory function in micro (resistance) vessels typically precedes those in macro (conduit) vessels, it is necessary to investigate the molecular adaptations to physical activity in both vascular beds in obesity. Thus, the purpose of this dissertation was to elucidate the underlying mechanism(s) by which physical activity ameliorates NLRP3 inflammasome-associated endothelial dysfunction in obesity. We hypothesized that physical activity would attenuate the obesity-induced inflammasome signaling responsible for endothelial dysfunction in the resistance and conduit vessels. To test our hypothesis, we used C57BL/6J male mice provided with high-fat diet (HFD) to develop diet-induced obese model simultaneously with voluntary running wheel to mimic natural physical activity in humans. We investigated the inflammasome signaling pathway, NO, and oxidative stress-associated molecular mechanisms in the resistance vessels (coronary arterioles) and conduit (aorta) vessels in obese mice. Also, we explored putative mechanisms of the inflammasome-related vascular dysfunction via adiponectin (APN)-adiponectin receptor 1 (AdipoR1) axis, a potential inhibitor of inflammasome, and tight junction adaptors zonula occludens-1 (ZO-1) and ZO-2, downstream target of the inflammasome responsible for endothelial dysfunction. We found that coronary arteriole and aorta from HFD mice exhibit decreases in NO production and increases in oxidative stress, however, these alterations are corrected by voluntary running. In both coronary arteries and aorta from obese mice, voluntary running attenuates obesity-induced increase of active caspase-1 and IL-1β representative indicators of NLRP3 inflammasome activation. Voluntary running restores APN-AdipoR1 contents and ZO-1/2 expression in endothelial cells of the obese aorta. Thus, this study demonstrates that physical activity is protective against the inflammasome-mediated vascular dysfunction in obesity through restoring NO production, APN-AdiopoR1, and ZO-1/2 expression, and decreasing oxidative stress and the inflammasome.Item The Effect of Acute Eccentric Resistance Exercise on Immune Response to Influenza Vaccination in Older Adults(2022-05-02) Elzayat, Mahmoud Tarek Mostafa Abdelmeguid; LaVoy, Emily C.; Markofski, Melissa M.; Park, Yoonjung; Laughlin, Mitzi S.INTRODUCTION: Older adults are at risk for morbidity and mortality caused by influenza. Vaccination is the primary means of prophylaxis, but protection is often compromised in older adults. As resistance exercise mobilizes immune cells into muscle, it may enhance vaccination response. We aim to compare antibody titers and cell-mediated immune responses to influenza vaccination in older adults. Furthermore, we aim to compare those responses in groups that performed eccentric resistance exercise immediately prior to vaccination and a control group that did not exercise. We also aim to explore any correlations between perceived stress and those responses to influenza vaccine. METHODS: Twenty-nine resistance training-naive older adults (20 women, 73.9 ± 5.3 years) were randomized to 1 of 3 groups: vaccination in the same arm that exercised (Ex-S), vaccination in the opposite arm that exercised (Ex-Op), and seated rest (No-Ex). Exercise consisted of 10 sets of 5 eccentric unilateral repetitions at 80% of the pre-determined concentric one repetition maximum. Lateral raises were alternated with bicep curls. No-Ex sat quietly for 25 min. Following exercise or rest, all received the 2018 quadrivalent influenza vaccine in the non-dominant deltoid. Antibody titers against each influenza vaccine strain were determined by hemagglutinin inhibition (HI) assays at baseline, 6-and 24-weeks post-vaccination. Influenza-specific T-lymphocytes were quantified after stimulation with the vaccine by intracellular cytokine staining. Relationship between perceived stress and antibody titers and cell-mediated immunity was determined through correlation analysis. RESULTS: HI assay results were not different in geometric mean across groups or across timepoints. There were also no differences in antibody titer fold-change between groups. Groups did not differ in cell-mediated immunity at baseline, 6-weeks and 24-weeks. Perceived stress demonstrated a positive correlation with antibodies against the A/H1N1 strain at 6-weeks only. Perceived stress was also positively correlated with cell-mediated immunity at baseline, but not in the later visits. CONCLUSIONS: A single bout of eccentric resistance exercise performed in the vaccinated arm or the opposite arm did not improve the effectiveness of influenza vaccination. Baseline levels of perceived stress had little impact on antibody titers or cell-mediated immunity in older adults following vaccination.Item The Effect of Exercise on Endoplasmic Reticulum Stress-Associated Vascular Dysfunction(2019-12) Hong, Jun Young; Park, Yoonjung; O'Connor, Daniel P.; Markofski, Melissa M.; Marrelli, Sean P.Atherosclerosis and Alzheimer’s disease (AD) constitute a high health threat worldwide. Endothelial dysfunction is generally known as an early pathogenic response in atherosclerosis and a major culprit for the development of AD. Chronic endoplasmic reticulum (ER) stress in endothelial cells contributes to endothelial dysfunction with an increase in oxidative stress, inflammation, and apoptosis, which leads to cell death. Alleviation of ER stress in the vascular system can be an important therapeutic strategy for retardation and treatment of pathophysiology response in atherosclerosis and AD. Exercise training is considered to be frontline therapy for prevention and treatment of vascular dysfunction through the mitigation of oxidative stress and the inflammatory and apoptotic response in cardiovascular and neurodegenerative diseases. However, the role of exercise training in ER stress-associated vascular dysfunction in different vascular beds and its underlying mechanism in atherosclerosis and AD is still largely unknown. Therefore, the central aim of the dissertation study was to identify the underlying mechanisms by which exercise training mitigates ER stress-associated vascular dysfunction in different vascular beds and pathologies. To achieve the central aim of study, we investigated a comprehensive understanding of exercise effects on ER stress-associated endothelial dysfunction in different vascular beds (mesenteric artery and coronary arterioles) in atherosclerosis and on its molecular mechanisms. In addition, we explored the in-depth knowledge of the exercise effect on ER stress and purinergic receptor-associated cerebrovascular dysfunction using isolated intact posterior cerebral artery (PCA) from the transgenic mice model of AD and cultured human brain microvascular endothelial cells (HBMECs). To measure vascular function, we isolated the mesenteric arteries and coronary arterioles from ApoE knock-out mice for atherosclerosis and PCA from APP/PS1 double transgenic mice for AD. Also, we utilized programmed treadmill running as an exercise training intervention. To find an in-depth understanding of the exercise-induced effects at the cellular level, HBMECs were exposed to laminar shear stress (LSS). Our study demonstrates that ER stress impaired ACh-induced endothelial function in both mesenteric arteries and coronary arterioles of atherosclerosis through the reduction of eNOS expression and abnormal expression of ER stress markers, TXNIP/NLRP3 inflammasome, apoptosis, and oxidative stress. However, exercise training ameliorated ER stress-associated endothelial dysfunction in both vascular beds by reversing these abnormal molecular signaling pathways. In AD, ER stress impairs cerebrovascular function via the diminished eNOS expression, and increased ER stress markers and apoptosis expressions in AD mice brain, but exercise training improved cerebrovascular dysfunction by dampening these negative signaling cascades. Furthermore, ATP induced vasoconstriction in PCA from AD mice through the attenuation of eNOS and P2Y2 receptor expressions in AD mice brain. However, exercise training reversed ATP-induced vasoconstriction to vasodilation in PCA from AD mice with an increase in P2Y2 receptor-mediated eNOS signaling pathway in AD mice brain. Likewise, LSS upregulated the eNOS signaling and P2Y2 receptor expression in HBMECs, but inhibition of P2Y2 receptor blunted eNOS expression in LSS-induced HBMECs. The findings of this study will provide novel insight into the protective and therapeutic effect of exercise on ER stress- and purinergic receptor-associated vascular disease in atherosclerosis and AD.Item The Effect Of Human Peripheral Blood Mononuclear Cells Mobilized By Acute Exercise On Graft-Versus-Host Disease And Graft-Versus-Leukemia In A Humanized Mouse Model(2020-12) Diak, Douglass M; Simpson, Richard J.; LaVoy, Emily C.; Park, Yoonjung; Katsanis, EmmanuelHematopoietic cell transplantation and adoptive transfer immunotherapy are critical therapeutic options for patients with hematological malignancies. The lymphocyte composition of the donor graft is known to influence the potentially fatal graft-versus-host disease (GvHD) and the potentially curative graft-versus-tumor (GvT) effects. Increased numbers of NK-cells and γδ T-cells relative to naïve subsets of CD4+ and CD8+ αβ T-cells have been shown to evoke strong GvT effects with minimal GvHD. As single exercise bouts are known to produce these desirable shifts in lymphocyte subset composition, we hypothesized that human immune cells collected from a single bout of exercise will improve engraftment, GvHD, and GvT outcomes when compared to immune cells from rest when xenotransplanted to immunodeficient mice. This dissertation was divided into two specific hypotheses: 1) determine the effect of PBMCs collected during exercise on engraftment and GvHD in a humanized mouse model; and 2) determine the impact of PBMCs collected during exercise on GvT in a humanized mouse model. To test these hypotheses, 12 healthy adults completed a 30-minute bout of exercise that was 15% about their calculated ventilatory threshold. Blood was collected at rest and immediately prior to exercise cessation. Lymphocyte subtypes were determined by flow cytometry prior to transplant. 1 x 107 Human PBMCs and/or 1 x 106 human K562-luc2 leukemia cells were injected intravenously into 8-12 week old NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(IL15)1Sz/SzJ (NSG-Tg(Hu-IL15) or NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG). Engraftment of human immune cells was tracked weekly, while morbidity scoring and bioluminescence imaging was conducted twice per week for up to 40 days. In support of the hypotheses, tumor-bearing NSGIL-15 mice injected with PBMCs from exercise maintained increased percentages of NK cells and decreased percentages of CD4+ T cells for up to two weeks post-inoculation. Additionally, these mice displayed overall better survival, delayed severe morbidity (GvHD), and an overall reduction in tumor growth compared to mice injected with PBMCs collected from rest. However, improvements in engraftment, morbidity, and survival were not replicated in mouse models of mild or severe GvHD indicating that tumor activation of exercise immune cells was essential for improved outcomes compared to immune cells taken from rest. We conclude that exercising donors prior to transplants can improve disease outcomes for hematopoietic cell transplantations in cancer immunotherapies.Item THE EFFECT OF SIMULATED MICROGRAVITY ON ANTI-CMV AND ANTI-LEUKEMIA IMMUNE RESPONSES IN VITRO AND IN VIVO(2020-08) Mylabathula, Preteesh Leo; Markofski, Melissa M.; Simpson, Richard J.; Park, Yoonjung; Katsanis, EmmanuelAs the National Aeronautics and Space Administration (NASA), plans to return to the moon and send humans to Mars, crew health and safety concerns need to be examined with a focus on longer duration exploratory class missions. One of the transient changes that has been observed during the ISS missions is dysregulation of immune system. Latent viral reactivation and diminished cellular mediated immunity along with a TH2-cytokine shift being the consistently observed effects of spaceflight on immune system. However, most of the changes observed in spaceflight are a composite effect of stress, microgravity, radiation, circadian disruption, altered nutrition, and sleep disturbances, all of which have an immune-altering effect. Discerning precise effects of the various components of spaceflight become crucial to devise appropriate countermeasures. Ground-based simulated microgravity systems can be used to understand the specific effects of microgravity on human immune system. Rotary cell culture system (RCCS) is a NASA validated ground-based model to simulate microgravity. Using this quiescent low-shear stress environment, human immune cells can be exposed to simulated microgravity (SMG) for brief periods by randomizing the gravity vector and facilitating continuous free fall. In short-term spaceflight, latent viral reactivation along with lowered viral-specific T cell function has been recorded. Healthy functioning of viral-specific T cells is a prerequisite to controlling viral infections. So, it becomes imperative to examine if microgravity plays a role in this reduction of viral-specific T-cell function. There is also a paucity of data on effect of spaceflight and simulated microgravity on γδ-T cells. These crucial effector lymphocytes are considered a connecting link between innate and adaptive immune system. Their function in spaceflight, especially Vγ9Vδ2 T cell subset, becomes important to control hematological malignancies in early stages. Therefore, this dissertation examined the effect of simulated microgravity on expansion potential and function of viral specific T-cells and γδ-T cells. Exposure to SMG impaired in vitro expansion of CMV-specific T-cells (RM ANOVA, F(1.571, 6.283)= 8.367, p=0.0198). 10-million PBMCs at day1 of the expansion in SMG-exposed condition yielded 17.63±3.75 million (MEAN±SEM, N=5) CMV-specific T-cells at the end of the expansion. In comparison, STATIC-1G control cells expanded to 33.8±7.57 million, while 1G-rotational control exposed cells expanded to 28.32±7.21 million cells. However, exposure to SMG did not affect in vitro function of CMV-specific T-cells (RM ANOVA, F(1.357,12.21)=0.7434, p=0.4457). Hundred thousand cytotoxic (CD8+) CMV-specific T-cells exposed to SMG at the end of expansion killed 804.6±166.3 (MEAN±SEM, N=10) autologous PHA blasts pulsed with CMV peptides. In comparison, 1G-control and 1G-rotational control killed 909.2±160.6 and 669.7±125 PHA blasts respectively. Exposure to SMG also impaired in vitro expansion of γδ-T cells (Wilcoxon signed ranks test, p=0.039). 10 million PBMCs at day 1 of the expansion in SMG-exposed condition yielded 102.3±23.07 million (MEAN±SEM, N=9) γδ-T cells at the end of the expansion. In comparison, 1G-control PBMCs yielded 113.7±23.91 million γδ-T cells. Γδ-T cells that were exposed to SMG and later expanded in 1G showed downregulation of inhibitory receptor CD158b (paired t-test, p=0.03) and killed more U266 target cells (paired t-test, p=0.04) compared to γδ-T cells that were expanded in 1G. Exposure to SMG upregulated activating receptor NKG2D on γδ-T cells that were expanded in 1G (Wilcoxon matched-pairs signed rank test, p=0.0078), without concomitant increase in function. Exposure to SMG did not impair γδ-T cells’ ability to kill tumor target cells (K562: paired t-test, t(8) =0.5032, p=0.628; U266: paired t-test, t(8) =0.1479, p=0.886). Another limitation of spaceflight data is lack of in vivo functional data. Although we have observed decreased in vitro function of various immune cells in several flight and ground-based simulation studies, how this translates to a more physiologically relevant in vivo model remains to be explored. Ergo, this dissertation also improved upon the current in vitro data by examining how exposure to SMG using a RCCS, affects in vivo anti-leukemia activity of human effector lymphocytes. A humanized NSG-tg(hu-IL15) mice model, which is used in a pre-clinical setting for hematopoietic stem cell transplantation studies, was used to examine the in vivo effect of exposure to SMG on PBMCs. Furthermore, we examined the efficacy of Zoledronic acid+IL2 (ZOL+IL2) therapy as a possible spaceflight countermeasure to revive the in vivo anti-leukemia activity of SMG exposed PBMCs. ZOL+IL2 is a clinical therapeutic strategy to accelerate favorable immune reconstitution. This therapy also improves NK cell and γδ-T cell activity in vivo, after a hematopoietic stem cell transplantation. Therefore, we expected administration of ZOL+IL2 to abrogate the effect of exposure to SMG on human PBMCs, by stimulating NK cells and γδ-T cells. Exposure to SMG impaired anti-leukemia activity of human immune cells in vivo. Tumor growth control was compared between mice that were injected with PBMCs exposed to SMG (TUMOR+SMG PBMCs) or 1G-control (TUMOR+1G PBMCs) to evaluate the effect of SMG on anti-leukemia activity of human immune cells in vivo. Mice injected with tumor cells only was used as a reference for unrestrained tumor growth. Bioluminescent intensity (BLI) score was used as a measure of tumor burden. A mixed effects model was used to analyze BLI scores with ‘condition’ (TUMOR control, TUMOR+SMG PBMCs, TUMOR+1G PBMCs) and ‘time’ as main effects and an interaction term ‘condition*time’ in the model. This revealed that tumor grew differentially over time in different conditions. A pairwise comparison revealed that 1G-exposed PBMCs controlled tumor growth better than SMG-exposed PBMCs (p<0.001). Peak BLI reached during the experiment further understated the inability of SMG-exposed PBMCs to control tumor growth (Friedman test, p=0.0018, N=12, TUMOR+SMG PBMCs>TUMOR+1G PBMCs). Exposure to SMG did not alter engraftment, survival or graft-versus-host-disease (GVHD) dynamics. ZOL+IL2 therapy improved anti-leukemia activity of human immune cells in vivo. Mice that received SMG PBMCs and given ZOL+IL2 therapy controlled their tumor better compared to mice that received SMG PBMCs without ZOL+IL2 therapy (Mixed effects model, p=0.0004). There were no differences in tumor control between mice that received SMG PBMCs along with ZOL+IL2 therapy and mice that received 1G-exposed PBMCs. This showed that ZOL+IL2 therapy abrogated the loss of in vivo function after exposure to SMG. ZOL+IL2 therapy did not alter survival and GVHD dynamics. There were non-significant increases in NK cell and γδ-T cell engraftment throughout the experiment in blood of the animals, showing that ZOL+IL2 therapy improved anti-leukemia effector immune cell engraftment, which helped in tumor control. In summary, these experiments advance our understanding of the effect of simulated microgravity on immune cells. Exposure to SMG detrimentally affects immune cell function and expansion potential both in vitro and in vivo. These negative effects could impair crew health and performance during an exploratory class missions. These experiments also highlight the importance of microgravity as a contributor to the immune dysregulation observed in spaceflight. Future studies should explore the sustenance of this detrimental effect in confluence with other perturbations of spaceflight. Future investigations should also include relevant immunotherapeutic countermeasures to improve crew health and performance during long-duration exploration class missions.Item The Effects of VO2max on Levels of Testosterone as Males Age(2016-05) Rahman, Mohammed S.; Simpson, Richard J.; Markofski, Melissa M.; Park, Yoonjung; Jennings, KristoferPurpose: The reduction of Testosterone secretion by the gonads is “hypogonadism” and development of age-related hypogonadism is known as “late-onset hypogonadism”. Late-onset hypogonadism is characterized by issues such as osteoporosis, Alzheimer’s disease, frailty, obesity, cardiac failure and ischemic heart disease. The purpose of this investigation was to determine the impact of ⩒O2max on age-related declines in free and bound plasma testosterone levels in healthy men. Methods: A total of 45 male subjects of various ethnicities aged 20-62 years participated in this study. Resting blood samples were collected, after which subjects were on cycle ergometer. Subjects started the trail and complete four three-minute heart rate adjusted incremental stages. The ⩒O2max of each subject was estimated using a sub-maximal cycling exercise protocol. Free and Bound testosterone was then removed from blood serum samples and measured. Results: High levels of aerobic fitness did not offset age-related declines in circulating levels of free testosterone. While significant differences were found amongst the Young population (Low aerobic fitness versus High aerobic fitness) (p=0.045, F=2.912), this was not relevant to the investigation. Conclusion: After controlling for age, aerobic fitness did not prevent the age-associated decline in Testosterone. Taking the results of this study into consideration when creating countermeasures for older adult males with symptoms of hypogonadism, it is suggested that an exercise countermeasure have a combination of endurance and strength training to help mediate levels of testosterone with age.