Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition.

Unlabelled: Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be harvested and manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human γδ T-cells mobilized to blood in response to just 20 minutes of graded exercise have surface phenotypes and transcriptomic profiles associated with cytotoxicity, adhesion, migration, and cytokine signaling.

Human milk oligosaccharides reduce necrotizing enterocolitis-induced neuroinflammation and cognitive impairment in mice.

Necrotizing enterocolitis (NEC) is the leading cause of morbidity and mortality in premature infants. One of the most devastating complications of NEC is the development of NEC-induced brain injury, which manifests as impaired cognition that persists beyond infancy and which represents a proinflammatory activation of the gut-brain axis. Given that oral administration of the human milk oligosaccharides (HMOs) 2'-fucosyllactose (2'-FL) and 6'-sialyslactose (6'-SL) significantly reduced intestinal inflammation in mice, we hypothesized that oral administration of these HMOs would reduce NEC-induced brain injury and sought to determine the mechanisms involved.

Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile and exert enhanced graft-versus-leukemia effects in xenogeneic mice.

Background: Every bout of exercise mobilizes and redistributes large numbers of effector lymphocytes with a cytotoxic and tissue migration phenotype. The frequent redistribution of these cells is purported to increase immune surveillance and play a mechanistic role in reducing cancer risk and slowing tumor progression in physically active cancer survivors. Our aim was to provide the first detailed single cell transcriptomic analysis of exercise-mobilized lymphocytes and test their effectiveness as a donor lymphocyte infusion (DLI) in xenogeneic mice engrafted with human leukemia.

IL-2 and Zoledronic Acid Therapy Restores the Anti-Leukemic Activity of Human Lymphocytes Pre-Exposed to Simulated Microgravity.

Background: We have previously shown that the anti-tumor activity of human lymphocytes is diminished after 12-hours pre-exposure to simulated microgravity (SMG). Here we used an immunocompromised mouse model to determine if this loss of function would extend , and to also test the efficacy of IL-2 and zoledronic acid (ZOL) therapy as a potential countermeasure against SMG-induced immune dysfunction. We adoptively transferred human lymphocytes that were exposed to either SMG or 1G-control into NSG-Tg (Hu-IL15) mice 1-week after they were injected with a luciferase-tagged human chronic myeloid leukemia (K562) cell line.

The role of L-type amino acid transporter 1 () during in vitro myogenesis.

Satellite cells are required for muscle regeneration, remodeling, and repair through their activation, proliferation, and differentiation; however, how dietary factors regulate this process remains poorly understood. The L-type amino acid transporter 1 (LAT1) transports amino acids, such as leucine, into mature myofibers, which then stimulate protein synthesis and anabolic signaling. However, whether LAT1 is expressed on myoblasts and is involved in regulating myogenesis is unknown.

Salutary effects of moderate but not high intensity aerobic exercise training on the frequency of peripheral T-cells associated with immunosenescence in older women at high risk of breast cancer: a randomized controlled trial.

Background: Immunosenescence is described as age-associated changes within the immune system that are responsible for decreased immunity and increased cancer risk. Physically active individuals have fewer 'senescent' and more naïve T-cells compared to their sedentary counterparts, but it is not known if exercise training can rejuvenate 'older looking' T-cell profiles. We determined the effects of 12-weeks supervised exercise training on the frequency of T-cell subtypes in peripheral blood and their relationships with circulating levels of the muscle-derived cytokines (i.

Acute exercise increases immune responses to SARS CoV-2 in a previously infected man.

Evidence is emerging that exercise and physical activity provides protection against severe COVID-19 disease in patients infected with SARS-CoV-2, but it is not known how exercise affects immune responses to the virus. A healthy man completed a graded cycling ergometer test prior to and after SARS-CoV-2 infection, then again after receiving an adenovirus vector-based COVID-19 vaccine. Using whole blood SARS-CoV-2 peptide stimulation assays, IFN-γ ELISPOT assays, flow cytometry, viral-specific T-cell expansion assays and deep T-cell receptor (TCR) β sequencing, we found that exercise robustly mobilized highly functional SARS-CoV-2 specific T-cells to the blood compartment that recognized spike protein, membrane protein, nucleocapsid antigen and the B.

Exercise and adrenergic regulation of immunity.

Exercise training has a profound impact on immunity, exerting a multitude of positive effects in indications such as immunosenescence, cancer, viral infections and inflammatory diseases. The immune, endocrine and central nervous systems work in a highly synergistic manner and it has become apparent that catecholamine signaling through leukocyte β-adrenergic receptors (β-ARs) is a key mechanism by which exercise mediates improvements in immune function to help mitigate numerous disease conditions. Central to this is the preferential mobilization and redistribution of effector lymphocytes with potent anti-viral and anti-tumor activity, their interaction with muscle-derived cytokines, and the effects of catecholamine signaling on mitochondrial biogenesis, immunometabolism and the resulting inflammatory response.

The impact of high-intensity interval exercise training on NK-cell function and circulating myokines for breast cancer prevention among women at high risk for breast cancer.

Purpose: Preclinical evidence suggests that natural killer cell (NK-cell) function and myokines facilitate the protective effects of exercise for breast cancer prevention. Since higher-intensity exercise acutely promotes greater mobilization and larger changes in NK-cell cytotoxicity than lower-intensity, high-intensity interval training (HIIT) might offer increased immune protection compared to moderate-intensity continuous-training (MICT). This study compared a 12-week HIIT program to a 12-week MICT program and usual care on changes in resting NK-cell function and circulating myokines among women at high risk for breast cancer.

A Carbohydrate Beverage Reduces Monocytes Expressing TLR4 in Children with Overweight or Obesity.

Background: Childhood obesity is increasing, with about one-third of children overweight or obese. Obesity is characterized by a state of chronic low-grade inflammation that is related to cardiometabolic comorbidities. Inflammatory monocytes, which are classified into 3 different groups-classical, intermediate, and nonclassical monocytes, with Toll-like receptor 4 (TLR4+) expression indicating a proinflammatory state-underlie several obesity-associated morbidities.

Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity?

Remodelling of the immune system with age - immunosenescence - is a substantial contributor to poor health in older adults, with increasing risk of infections, cancer and chronic inflammatory disease contributing to age-related multi-morbidity. What is seldom considered when examining the immune response of an aged individual is that the immune system is profoundly influenced by physical activity. Habitual physical activity levels decline with age, with significant consequences for muscle mass and function.

Dietary Fiber Is Independently Related to Blood Triglycerides Among Adults with Overweight and Obesity.

Background: Metabolic syndrome (MetS), a cluster of visceral adiposity-related risk factors, affects approximately 35% of the United States population. Although improvement in diet quality is an important approach to reducing MetS risk, the role of particular dietary components remains unclear, especially among younger adults. Individual dietary components have been implicated in ameliorating or exacerbating MetS risk; however, the extent to which these factors contribute to MetS prevention has received little attention.

Oral Glucose Tolerance is Associated with Neuroelectric Indices of Attention Among Adults with Overweight and Obesity.

Objective: This study aimed to elucidate the relationship between glucose levels and insulin resistance and sensitivity obtained from oral glucose tolerance tests and neurophysiological indices of attention among adults with overweight and obesity.

Methods: Forty adults with overweight or obesity (BMI ≥ 25 kg/m ) underwent dual-energy x-ray absorptiometry to assess visceral adipose tissue. Repeated venous blood samples were collected during an oral glucose tolerance test to measure insulin resistance (homeostatic model assessment of insulin resistance) and indices of insulin sensitivity (Matsuda index and Stumvoll metabolic clearance rate).

Effects of endurance exercise training on inflammatory circulating progenitor cell content in lean and obese adults.

Key Points: Chronic inflammation underlies many of the health decrements associated with obesity. Circulating progenitor cells can sense and respond to inflammatory stimuli, increasing the local inflammatory response within tissues. Here we show that 6 weeks of endurance exercise training significantly decreases inflammatory circulating progenitor cells in obese adults.

Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans.

Purpose: Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of 6 wk of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls before outcome variable collection.

Methods: Thirty-two lean (n = 18 [9 female]) and obese (n = 14 [11 female]), previously sedentary subjects participated in 6 wk of supervised, endurance-based exercise training (3 d·wk) that progressed from 30 to 60 min·d and from moderate (60% of HR reserve) to vigorous intensity (75% HR reserve).

Protein-Rich Food Ingestion Stimulates Mitochondrial Protein Synthesis in Sedentary Young Adults of Different BMIs.

Context: Excess fat mass may diminish the anabolic potency of protein-rich food ingestion to stimulate muscle protein subfractional synthetic responses. However, the impact of adiposity on mitochondrial protein synthesis (MPS) rates after protein-rich food ingestion has not been thoroughly examined in vivo in humans.

Objective: We compared basal and postprandial MPS and markers of muscle inflammation [toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein 88 (MyD88) protein content] in young adults with different body mass indices (BMIs).

Circulating Progenitor Cell Response to Exercise in Wheelchair Racing Athletes.

Introduction: Circulating progenitor cells (CPC) are a heterogeneous population of stem/progenitor cells in peripheral blood that participate in tissue repair. CPC mobilization has been well characterized in able-bodied persons but has not been previously investigated in wheelchair racing athletes. The purpose of this study was to characterize CPC and CPC subpopulation mobilization in elite wheelchair racing athletes in response to acute, upper-extremity aerobic exercise to determine whether CPC responses are similar to ambulatory populations.

Hematopoiesis with Obesity and Exercise: Role of the Bone Marrow Niche.

Hematopoietic stem and progenitor cells (HSPC), the most primitive cells of the hematopoietic system responsible for maintaining all mature blood cells, display the hallmark characteristics of self-renewal and multi-potent differentiation into mature cell lineages. HSPC activity is directed by the bone marrow niche, a complex environment composed of heterogeneous cell populations that regulate HSPC function through the secretion of a wide array of cytokines and growth factors. Diet induced obesity results in a dramatic remodeling of the bone marrow niche, skewing HSPC function resulting in a compromised immune system.

Kinetics of circulating progenitor cell mobilization during submaximal exercise.

Circulating progenitor cells (CPCs) are a heterogeneous population of stem/progenitor cells in peripheral blood that includes hematopoietic stem and progenitor cells (HSPCs and HSCs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs) that are involved in tissue repair and adaptation. CPC mobilization during exercise remains uncharacterized in young adults. The purpose of this study was to investigate the kinetics of CPC mobilization during and after submaximal treadmill running and their relationship to mobilization factors.

Circulating progenitor cells are positively associated with cognitive function among overweight/obese children.

Recent evidence has indicated that overweight/obese children may experience cognitive and immune dysfunction, but the underlying mechanisms responsible for the association between overweight/obesity, immune dysfunction, and cognition have yet to be established. The present study aimed to identify a novel link between obesity-induced immune system dysregulation and cognition in preadolescent children. A total of 27 male children (age: 8-10years) were recruited and separated by body mass index (BMI) into healthy weight (HW: 5th-84.

Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization.

Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection.

Acute exercise mobilizes hematopoietic stem and progenitor cells and alters the mesenchymal stromal cell secretome.

Transplantation of hematopoietic stem and progenitor cells (HSPC), collected from peripheral blood, is the primary treatment for many hematological malignancies; however, variable collection efficacy with current protocols merits further examination into factors responsible for HSPC mobilization. HSPCs primarily reside within the bone marrow and are regulated by mesenchymal stromal cells (MSC). Exercise potently and transiently mobilizes HSPCs from the bone marrow into peripheral circulation.